WO2003056329A2 - Utilisation d'un complexe de transduction de signal dans des processus de mise au point de medicaments - Google Patents

Utilisation d'un complexe de transduction de signal dans des processus de mise au point de medicaments Download PDF

Info

Publication number
WO2003056329A2
WO2003056329A2 PCT/DK2002/000901 DK0200901W WO03056329A2 WO 2003056329 A2 WO2003056329 A2 WO 2003056329A2 DK 0200901 W DK0200901 W DK 0200901W WO 03056329 A2 WO03056329 A2 WO 03056329A2
Authority
WO
WIPO (PCT)
Prior art keywords
protein
domain
domains
signal transduction
adaptor
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/DK2002/000901
Other languages
English (en)
Other versions
WO2003056329A3 (fr
Inventor
Thue W. Schwartz
Birgitte Holst Lange
Arne Heydorn
Rasmus JØRGENSEN
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
7TM Pharma AS
Original Assignee
7TM Pharma AS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 7TM Pharma AS filed Critical 7TM Pharma AS
Priority to AU2002357449A priority Critical patent/AU2002357449A1/en
Publication of WO2003056329A2 publication Critical patent/WO2003056329A2/fr
Publication of WO2003056329A3 publication Critical patent/WO2003056329A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/502—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects
    • G01N33/5041—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing non-proliferative effects involving analysis of members of signalling pathways
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6872—Intracellular protein regulatory factors and their receptors, e.g. including ion channels
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors

Definitions

  • the present invention relates to the use of a signal transduction complex in drug discovery processes.
  • the signal transduction complex is an assembly or combination of peptides or proteins comprising a biological target molecule and one or more downstream effector molecules, at least one of which has been modified to contain one or more domains and/or one or more recognition motifs.
  • the signal transduction complex is responsible for exerting a signal transduction process.
  • the complex may also comprise one or more endogenous and/or non-endogenous adaptor molecules that are able to connect or link the biological target molecule and the downstream effector molecules together.
  • the present invention it is possible to ensure that a given biological target molecule will participate in an efficient signal transduction process, which is suited for use in drug discovery processes. It is, for example possible to improve the signal transduction process for a biological target molecule, which otherwise could not or only poorly be used in drug discovery, or to make a given biological target molecule signal trough a signal transduction pathway, which it normally would not be able to use and which is particularly suited for use in a drug discovery process.
  • Hormones and transmitters acting through membrane receptors exert their effect by binding to the receptor and thereby inducing or selecting an active conformation and starting a signal transduction process.
  • the active conformation of the receptor is recognized by downstream effector molecules - i.e. usually intracellular or membrane associated proteins such as enzymes and ion channels - in which an active conformation is thereby induced or selected.
  • the active conformation of either the receptor and or of one or more of the downstream molecules will lead to an intracellular signal.
  • This signal can be an increase or decrease in the concentration of an intracellular, chemical messenger, for example a product or a substrate of an enzyme (such as cyclic AMP or inositol triphosphates).
  • the signal can, for example, also be an increase or decrease in the concentration of a cytosolic ion resulting from an altered activity or state of an ion-channel being located either in the cell membrane of in the membrane of an intracellular compartment.
  • a down stream effector molecule could be the inositol triphosphate receptor (IP3 receptor), which is a ligand (IP3) gated Ca ++ channel located in the membranes of the calcium stores of the endoplasmatic reticulum inside the cell.
  • IP3 receptor inositol triphosphate receptor
  • IP3 a ligand
  • the first downstream molecules in the signal transduction process will be the cell surface receptor followed by a heterotrimeric G protein (of the Gq/G11 type) followed by phospholipase C and its product, IP3.
  • Therapeutic compounds - drug substances often act by binding to biological target molecules, for example surface receptors, and thereby they either stabilize an inactive conformation of these thereby preventing the hormone or transmitter from exerting its effect (antagonists or blockers); or, the drug stabilizes an active conformation of the receptor and thereby mimics the function of the hormone or transmitter (agonists).
  • An important, early part of the drug discovery process is often to identify compounds that either interfere with the binding of the hormone or transmitter to the receptor or to identify compounds, which will block or induce the signal transduction process.
  • Such functional assays where the effect of a compound on the signal transduction process is measured - as opposed to binding assays - are often preferred in the drug discovery process, since they better reflect the action of the compound on the receptor in cells in the whole body.
  • the compounds are tested in various forms of in vitro signal transduction assays, where the biological target molecule, the receptor is expressed in a cellular context which intend to mimic the cellular setting in which the receptor normally functions in the body. In practice, this is usually performed by heterologous expression of the human receptor in a eukaryotic, laboratory cell line, for example CHO (Chinese hamster ovary) cells or HEK293 (human embryonic kidney) cells.
  • CHO Choinese hamster ovary
  • HEK293 human embryonic kidney
  • the present invention is aimed at improving that.
  • the drug discovery process it would also be desirable to be able to place the biological target molecule on a chip - a so-called biochip. In this way the whole process could be miniaturized which could ensure a quicker and more efficient process.
  • many similar biological target molecules could be probed in parallel or in an array. This could be useful for testing the effect of compounds not only on the single biological target molecule but on a number of similar target molecules in order to probe for cross reactivity or selectivity etc.
  • Many soluble biological target molecules for example certain enzymes, DNA etc. can be placed on various forms of solid support in micro arrays and can in this form be used in a drug discovery process.
  • receptors are not found randomly distributed or freely floating around in the membrane and cytosol, but that they are organized mainly through protein-protein interactions in complexes or micro-domains, which could be considered to function as multi-molecular "machines". It appears, that receptors are rather selectively affecting effectors, which are located in the proximity of the receptor and not similar effectors located elsewhere in the cell. Proximity among the different proteins involved in a signal transduction process is important. This is even the case for small molecule second messengers, which apparently also act mainly through further downstream effectors found close to their place of production.
  • scaffolding or adaptor proteins which contain one or usually more (up to more than 10-15) binding domains, for example PDZ domains each of which have affinity for and will bind different recognition motifs or domains located in the various other signal-transduction molecules mentioned above.
  • Adaptor proteins may also interact with each other and they may interact for example with elements of the cytoskeleton.
  • PSD post synaptic density
  • CC-Homer proteins each of which consists of two domains: a leucine zipper motif and an EVH-1 domain, which can bind for example the C-terminal tail of metabotrobic glutamate receptors or can bind the IP3 receptor (see Figure 2).
  • the CC- Homers form dimers because the leucine zipper motifs will make a coil-coil (CC) structure with a similar motif from another homer protein (see Figure 2).
  • CC-Homer dimers can act as adaptor proteins linking for example metabotropic glutamate receptors located in the cell surface membrane with the downstream effector molecule, the IP3 receptor, which is found in the calcium stores of the ER.
  • the present invention is directed towards creating signal transduction complexes, which are suited for drug discovery processes, by altering the biological target molecule and/or adaptor proteins and/or downstream effector molecules.
  • the idea is, to use adaptor proteins and especially domains from adaptor proteins as well as the domains and/or recognition motifs, which are recognized by the domains to construct artificial, efficient signal transduction complexes suited for drug discovery processes.
  • These signal transduction complexes can be used both in cellular settings and in in vitro settings such as biochips.
  • the present invention relates to a drug discovery process for identification of a ligand that is able to bind to a biological target molecule, the process comprising
  • a) constructing a signal transduction complex comprising a biological target molecule, one or more downstream effector molecules and, optionally, an adaptor protein, b) contacting the ligand with the signal transduction complex, and c) measuring any effect resulting from a signal transduction process relating to the biological target molecule and one or more of downstream effector molecules.
  • the signal transduction complex comprises a first component comprising a biological target molecule, a second component comprising one or more adaptor protein(s) and a third component comprising one or more downstream effector molecule(s), wherein each of the components recognizes or binds at least one of the other components to affect a signal transduction process.
  • the signal transduction complex comprises a first component comprising a biological target molecule and a second component comprising one or more downstream effector molecule(s), wherein each of the components recognizes or binds at least one of the other components to effect a signal transduction process.
  • biological target molecules normally function in cells in signal transduction complexes.
  • the molecular composition of these complexes is in the methodology used today in the industry determined by the natural occurrence of recognition motifs and/or domains on the biological target molecule, adaptor proteins, and downstream effector molecules in the cell in which the receptor is expressed for use in a drug discovery process - i.e. where the receptor is expressed normally or expressed heterologously after transfection.
  • One attempt, which is currently used to improve the signal transduction, is to co-transfect with various signal transduction proteins.
  • recognition motifs, domains and whole adaptor proteins are used as building blocks or LEGO® bricks to modify signal transduction molecules and thus alter and guide the protein-protein interactions among these molecules and thereby create new, efficient signal transduction complexes in which a given biological target molecule can function in an appropriate way to be used in drug discovery processes.
  • the receptor can, for example be driven to use a signal transduction pathway, which it normally does not use but which is especially suited for the drug discovery process. Or a receptor, which normally signals very poorly in the heterologous cellular expression system, can be structurally modified to become an efficient partner in an optimized signal transduction complex.
  • a receptor or one or more downstream effectors can simply be targeted to accumulate within the cell in a desired signal transduction complex by being decorated with appropriate recognition motifs and or domains. It will be obvious to the skilled person that further co-transfection, co-expression of various normal of modified signal transduction molecules along with the modified signal transduction molecules could be needed or could further improve the signal transduction process.
  • recognition motifs, domains or whole adaptor proteins are further optimized by genetic manipulation and selection performed according to methods well known to a person skilled in the art in order to increase the affinity and/or the selectivity and thereby improve their binding properties in order for them to be used as more efficient building blocks in the creation of signal transduction complexes.
  • the signal transduction complex is being built outside a cell for example on a biochip.
  • One of the current problems in using membrane proteins on solid supports for example in protein array systems is to create a suitable lipid membrane environment where the membrane protein can function normally.
  • the building of signal transduction complexes outside the cell for example on a biochip can also be used for non-membrane biological target molecules, for example nuclear receptors where co-activators and or co-repressors could be kept in suitable proximity of the biological target molecule by decorating them or the biological target molecule with appropriate recognition motifs and/or domains.
  • a “drug discovery process” is a process for identifying a ligand that interacts with an endogenous or non-endogenous biological target molecule (see below).
  • a “ligand” is intended to include any substance that either inhibits or stimulates the activity of a biological target molecule and/or that competes for the biological target molecule in a binding assay.
  • An "agonist” is defined as a ligand increasing the functional activity of a biological target molecule.
  • An "antagonist” is defined as a ligand decreasing the functional activity of a biological target molecule either by inhibiting the action of an agonist or by its own intrinsic activity.
  • An “inverse agonist” (also termed “negative antagonist”) is defined as a ligand decreasing the basal functional activity of a biological target molecule
  • a “biological target molecule” is intended to include peptides, polypeptides, proteins, nucleoproteins, glycoproteins, lipoproteins and derivatives thereof.
  • the biological target molecule may be endogenous or non-endogenous or it may have been manipulated to contain a metal-ion binding site.
  • a “signal transduction process” is defined as the transmission of a signal from the biological target molecule to one or more downstream effector molecules.
  • the signal transduction process is initiated by the binding of a ligand to the biological target molecule.
  • “Signal transduction” is defined as a process by which information is communicated by a pathway initiated by binding of a ligand to a biological target molecule.
  • downstream effector molecule denotes an enzyme, ion channel or a transporter involved in a signal transduction process.
  • signal transduction complex is intended to mean an assembly or combination of proteins comprising one or more downstream effector molecules and a biological target molecule, at least one of which has been modified as described herein, and wherein a signal transduction process can take place.
  • the complex may also comprise one or more adaptor proteins that are able to link the signal transduction between the biological target molecule and the downstream effector molecules.
  • recognition motif refers to a relatively short amino acid sequence of from about 1 to about 20 amino acids such as, e.g. from about 2 to about 15, from about 2 to about 10, from about 2 to about 5 or from 2 to 4 amino acids; the amino acids may be natural or modified amino acids.
  • the recognition motif recognizes a protein domain or another recognition motif.
  • domain refers to a relatively short amino acid sequence of from about 20 amino acids to about 200 amino acids, that usually has a well-defined three-dimensional structure.
  • the domain is able to recognize and interact with a specific short amino acid sequence denoted a "recognition motif or with another domain (e.g. of the same or different kind).
  • adaptor protein describes a protein comprising one or more domains and/or one or more recognition motifs, thereby allowing the adaptor protein to interact with a biological target molecule and/or one or more adaptor proteins and/or a downstream effector molecule.
  • endogenous e.g. in the sense “endogenous biological target molecule” is intended to mean that the biological target molecule has a composition and a structure that equals that of the naturally occurring biological target molecule
  • non-endogenous e.g. in the sense “non-endogenous biological target molecule” is intended to mean that the biological target molecule has a composition and a structure that is different from that of the naturally occurring biological target molecule, e.g. by the introduction of a mutation and/or a domain and/or a adaptor protein and/or a recognition motif.
  • Amino acids are designated by the commonly used three-letter abbreviation or one-letter symbol.
  • the letter “X” may describe any amino acid.
  • the letter “p” in connection with an amino acid, e.g. "pY” denotes that the amino acid id phosphorylated.
  • a biological target molecule for use according to the present invention is a protein selected from the group consisting of membrane receptors, nuclear receptors, steroid receptors, intracellular receptors, transcription factors, enzymes, allosteric enzyme regulator proteins, growth factors, hormones, neuropeptides or immunoglobulins.
  • the protein may be a membrane protein optionally in the form of a homo- or heterodimer or in the form of a homo- or heterooligomer.
  • the membrane protein is an integral membrane protein such as, e.g. proteins comprising 1-14 transmembrane domains such as 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13 or 14 domains.
  • the membrane protein comprises 1 transmembrane domain it may be a receptor such as a tyrosine kinase receptor, e.g. a growth factor receptor such as the growth hormone, insulin, epidermal growth factor, transforming growth factor, erythropoietin, colony-stimulating factor, platelet-derived growth factor receptor or nerve growth factor receptor (TrkA or TrkB), the receptor optionally being in the form of a homo- or heterooligomer.
  • the membrane protein comprises 1 transmembrane domain and is a cell adhesion molecule, e.g. NCAM, VCAM or ICAM.
  • the membrane protein comprises 2 transmembrane domains and is a purinergic ion channel.
  • the membrane protein may also comprise 3, 4 or 5 transmembrane domains such as, e.g., a ligand-gated ion channel, such as a nicotinic acetylcholine receptor, GABA receptor, or glutamate receptor (NMDA or AMPA) or it may be a voltage-gated ion channel, such as a potassium, sodium, chloride or calcium channel.
  • a ligand-gated ion channel such as a nicotinic acetylcholine receptor, GABA receptor, or glutamate receptor (NMDA or AMPA)
  • NMDA or AMPA glutamate receptor
  • the membrane protein is a 7TM receptor, a G-protein coupled receptor, such as the receptor for (- in brachet: the receptor subtypes are mentioned): acetylcholine (m1-5), adenosine (A1-3) and other purines and purimidines (P2U and P2Y1-12), adrenalin and noradrenalin ( ⁇ 1A-D, ⁇ 2A-D and ⁇ 1-3), amylin, adrenomedullin, anaphylatoxin chemotactic factor, angiotensin (AT1A, -1 B and -2), apelin, bombesin, bradykinin (land 2), C3a, C5a, calcitonin, calcitonin gene related peptide, CD97, conopressin, corticotropin releasing factor (CRFIand -2), calcium, cannabinoid (CBIand - 2), chemokines (CCR1-11 , CXCR1-6,
  • the membrane protein is a transporter protein, such as, e.g. i) Na + cotransporters, including Na + ,CI " transporters, such as, e.g., GABA transporters, monoamine transporters, neutral amino acids transporters, kreatinin transporters and nucleoside transporters, and Na + ,K + coupled transporter such as, e.g., glutamate transporters, neutral amino acids transporters, and inositol transporters, and Na + , glucose cotransporters, and Na + ,K + ,CI " cotransporters, ii) H+ coupled transporter including oligopeptide transporters and multi drug transporters, iii) antiporters, including Na7H + - exchangers, anion exchangers such as, e.g., HCO 3 7CI " exchangers and Na7Ca + exchangers, iv) ion-transporting ATPases including Na + ,K + ATPase, H + ,
  • the membrane protein may also be an enzyme or an orphan receptor such as, e.g. a 7TM orphan receptor.
  • the biological target molecule for use according to the invention may be in the form of the endogenous biological target molecule or it may be on a non-endogenous form, i.e. the endogenous biological target molecule has been mutated or otherwise changed.
  • the biological target molecule may have been manipulated to contain a metal- ion binding site.
  • Tables 1 - 8 show a selection of various adaptor proteins suitable for use according to the present invention.
  • the adaptor proteins are all isolated from Homo sapiens, but the adaptor proteins used according to the invention are not limited to adaptor proteins originating from the human body.
  • the adaptor proteins used may be isolated from both prokaryotic cells, such as e.g. E. Coli or Bacillus or eukaryotic cells, such as, e.g. mammalian cells, yeast cells, plant cells and insect cells, such as, e.g., Drosophila cells.
  • the Tables 1-8 have been generated using SMART (Simple Modular Architecture Research Tool) at http://smart.embl-heidelberq.de
  • the numbers in the left column is the number of the proteins in the EMBL sequence database at http://www.ebi.ac.uk
  • Q9NPN8 (FRAGMENT) SOC7 HUMAN Suppressor of cytokine signaling 7 (SOCS-7) (Nek, Ash and phospho pase C gamma-binding protein) (Nck-associated protein 4) (NAP-4) (Fragment)
  • SH2 domain protein 2A T cell-specific adapter protein
  • TSAd T cell-specific adapter protein
  • SH2 VEGF receptor-associated protein
  • DJ823N20 1 1 V-SRC AVIAN SARCOMA (SCHMIDT-RUPPIN A-2) VIRAL ONCOGENE HOMOLOG (A
  • Ras GTPase-activating protein 1 Ras GTPase-activating protein 1 (GTPase-activating protein) (GAP) (Ras p21 protein activator)
  • RSG1 HUMAN p120GAP
  • RasGAP RasGAP
  • BLK HUMAN Tyrosine-protein kinase BLK (EC 2 7 1 112) (B lymphocyte kinase) (p55- BLK)
  • HCK HUMAN Tyrosine-protein kinase HCK (EC 2 7 1 112) (P59-HCK and P60-HCK) (Hemopoietic cell kinase)
  • SOCS-1 cytokine signaling 1
  • JAB JAT induced STAT inhibitor 1
  • PIG2 HUMAN Phosphohpase C-gamma-2 (PLC-IV)
  • N-chimae ⁇ n CHIN HUMAN N-chimae ⁇ n (NC) (N-chime ⁇ n) (Alpha chime ⁇ n) (A-chimae ⁇ n)
  • Lymphocyte cytoso c protein 2 (SH2 domain-containing leucocyte protein of 76 kDa) (SLP-76 tyrosine
  • JAK1 HUMAN Tyrosine-protein kinase JAK1 (EC 2 7 1 112) (Janus kinase 1) (JAK-1)
  • PIG1 HUMAN Phosphohpase C-gamma-1 (PLC-II) (PLC-148)
  • HUMAN T y rosine -P rotein kinase ZAP-70 (EC 2.7.1.112) (70 kDa zeta-associated protein) (Syk-related tyrosine kinase).
  • KSYK HUMAN Tyrosine-protein kinase SYK (EC 2.7.1.112) (Spleen tyrosine kinase).
  • GRBE HUMAN Growth factor receptor-bound protein 14 (GRB14 adapter protein).
  • DJ977B1.1 (NOVEL PROTEIN TYROSINE KINASE WITH SRC HOMOLOGY DOMAIN 2DOMAINS) uam js (FRAGMENT).
  • VAV2 HUMAN VAV-2 protein VAV2 HUMAN VAV-2 protein.
  • NCK1 HUMAN Cytoplasmic protein NCK1 (NCK adaptor protein 1 ) (SH2/SH3 adaptor protein NCK-alpha).
  • ABL2 HUMAN Tyrosine-protein kinase ABL2 (EC 2.7.1.112) (Tyrosine kinase ARG).
  • EAT2 HUMAN EWS/FLI1 activated transcript 2 (EAT-2).
  • FGR HUMAN Proto-oncogene tyrosine-protein kinase FGR (EC 2.7.1.112) (P55-FGR) (C-FGR).
  • PTK6 HUMAN Tyrosine-protein kinase 6 (EC 2.7.1.112) (Breast tumor kinase) (Tyrosine-protein kinase brk).
  • PTN6 HUMAN 1C Hematopoietic cell protein-tyrosine phosphatase
  • SH-PTP1 Protein-tyrosine phosphatase SHP-1
  • GRB7 adapter protein Epidermal growth factor receptor GRB-7 GRB7 HUMAN (B47)
  • GRB2 HUMAN Growth factor receptor-bound protein 2 GRB2 adapter protein
  • SH2/SH3 adapter GRB2 HUMAN Growth factor receptor-bound protein 2
  • TXK HUMAN Tyrosine-protein kinase TXK (EC 2 7 1 112)
  • TYK2 HUMAN Non-receptor tyrosine-protein kinase TYK2 (EC 2 7 1 112)
  • GRB10 adaptor protein Insulin receptor binding protein GRB- KDA ⁇ UMAN I D . IK
  • FYN HUMAN Proto-oncogene tyrosine-protein kinase FYN (EC 2 7 1 112) (P59-FYN) (SYN) (SLK)
  • CBLB HUMAN Signal transduction protein CBL-B (SH3-b ⁇ nd ⁇ ng protein CBL-B)
  • RTK MI i ⁇ N Tyrosine-protein kinase BTK (EC 2 7 1 112) (Bruton's tyrosine kinase) (Agammaglobulinaemia tyrosine B i ft HUMAN k
  • Beta-chimae ⁇ n (Beta-chime ⁇ n)
  • LCK HUMAN Proto-oncogene tyrosine-protein kinase LCK (EC 2 7 1 112) (P56-LCK) (LSK) (T cell-specific protein- tyrosine kinase)
  • NCK2 HUMAN Cytoplasmic protein NCK2 (NCK adaptor protein 2) (SH2 SH3 adaptor protein NCK-beta) (Nck-2)
  • JAK2 HUMAN Tyrosine-protein kinase JAK2 (EC 2 7 1 112) (Janus kinase 2) (JAK-2)
  • Tyrosine-protein kinase ITKTSK (EC 2 7 1 112) (T-cell-specific kinase) (Tyrosine-protein kinase Lyk)
  • GRB2-related adaptor protein 2 GRB2-related adaptor protein 2 (GADS protein) (Growth factor receptor binding protein) (GRBLG) (GRF40 C RP9 HI I ⁇ M ada P tor protein) (GRB-2-l ⁇ ke protein) (GRB2L) (GRBX) (P38) (Hematopoietic cell-associated adaptor KI- HUMAN prote
  • Phosphatidyhnositol 3-k ⁇ nase regulatory alpha subunit (PI3-k ⁇ nase p85-alpha subunit) (Ptdlns-3-k ⁇ nase
  • FES HUMAN Proto-oncogene tyrosine-protein kinase FES/FPS (EC 2 7 1 112) (C-FES)
  • C-FES CBLC HUMAN Signal transduction protein CBL-C (SH3-b ⁇ nd ⁇ ng protein CBL-C) (CBL-3)
  • BMX HUMAN Cytoplasmic tyrosine-protein kinase BMX (EC 2 7 1 112) (Bone marrow kinase BMX) (Epithelial and endothelial tyrosine kinase) (ETK) (NTK38)
  • JAK3 HUMAN Tyrosine-protein kinase JAK3 (EC 2 7 1 112) (Janus kinase 3) (JAK-3) (Leukocyte janus kinase) (L-JAK)
  • JNK-interactmg protein 1 JIP-1
  • JIP1 HUMAN scaffold protein 1 (lslet-bra ⁇ n-1 ) (IB-1) (Mitogen-activated protein kinase 8- ⁇ nteract ⁇ ng protein 1 )
  • Amyloid beta A4 precursor protein-binding family A member 2 Neuron-specific X11 L protein
  • APB2 HUMAN Mund 8-1 -interacting protein 2) (M ⁇ nt-2) (Adapter protein X11beta)
  • AAH27946 Similar to amyloid beta (A4) protein-binding, family B, member 2 (Fe65-l ⁇ ke protein) NUMB HUMAN NUMB PROTEIN HOMOLOG (H-NUMB) (PROTEIN S171) AAN32667 Tensin 3
  • Amyloid beta A4 precursor protein-binding family A member 1 Neuron-specific X11 protein
  • APB1 HUMAN Mund 8-1 -interacting protein 1 (M ⁇ nt-1) (Adapter protein X11 alpha)
  • APB3 HUMAN Amyloid beta A4 precursor protein-binding family A member 3 Neuron-specific X11 L2 protein
  • Neuron-specific X11 L2 protein Neuron-specific X11 L2 protein
  • Neuron-3 Neuron-specific X11 L2 protein
  • Neuront-3 Adapter protein X11gamma
  • NMBL HUMAN NUMB-LIKE PROTEIN (NUMB-R) TBC4 HUMAN TBC1 domain family member 4 Q96S48 THYROID SPECIFIC PTB DOMAIN PROTEIN Q8N4K5 Hypothetical protein ABB3 HUMAN Amyloid beta A4 precursor protein-binding family B member 3 (Fe65-l ⁇ ke protein 2)
  • DAB2 HUMAN Disabled homolog 2 (Differentially expressed protein 2) (DOC-2)
  • Adaptor protein APPL Synignaling adaptor protein DIP13alpha
  • DJ809F4 1 (NOVEL PROTEIN SIMILAR TO RAB6 GTPASE ACTIVATING PROTEIN ANDC ELEGANS
  • JNK-interactmg protein 2 JIP-2
  • JIP2 HUMAN scaffold protein 2) (lslet-bra ⁇ n-2) (IB-2) (Mitogen-activated protein kinase 8- ⁇ nteract ⁇ ng protein 2)
  • Ohgophren ⁇ n-1 like protein GTPase regulator associated with focal adhesion kinase
  • JNK-interacting protein 1 JIP-1
  • JIP1 HUMAN scaffold protein 1) (lslet-bra ⁇ n-1 ) (IB-1 ) (Mitogen-activated protein kinase 8- ⁇ nteract ⁇ ng protein 1 )
  • NCK2 HUMAN Cytoplasmic protein NCK2 (NCK adaptor protein 2) (SH2 SH3 adaptor protein NCK-beta) (Nck-2)
  • OTOR HUMAN Otoraplin precursor Fibrocyte-de ⁇ ved protein
  • Melanoma inhibitory activity like protein Melanoma inhibitory activity like protein
  • AAH35782 Similar to tyrosine kinase, non-receptor, 1
  • DJ1042K10 2 2 (NOVEL PROTEIN WITH PROBABLE RABGAP DOMAINS AND SRCHOMOLOGY
  • Tight junction protein ZO-1 (Zonula occludens 1 protein) (Zona occludens 1 protein) (Tight junction protein
  • AAH38105 Similar to membrane protein, palmitoylated 3 (MAGUK p55 subfamily member 3)
  • HCK HUMAN Tyrosine-protein kinase HCK (EC 2 7 1 112) (P59-HCK and P60-HCK) (Hemopoietic cell kinase)
  • VINE HUMAN VINEXIN SH3-CONTAINING ADAPTOR MOLECULE-1
  • SCAM-1 SCAM-1
  • MATK HUMAN Megakaryocyte-associated tyrosine-protein kinase (EC 2 7 1 112) (Tyrosine-protein kinase CTK) (Protein kinase HYL) (Hematopoietic consensus tyrosine-lacking kinase)
  • GRB2 HUMAN Growth factor receptor-bound protein 2 GRB2 adapter protein
  • SH2/SH3 adapter GRB2 HUMAN Growth factor receptor-bound protein 2
  • Rho-GTPase-activating protein 4 (Rho-GAP hematopoietic protein C1 ) (p115)
  • PIG2 HUMAN Phosphohpase C-gamma-2 (PLC-IV)
  • BA570J18 1 1 (NOVEL PROTEIN (KIAA0424) (POSSIBLE ORTHOLOG OF RAT COLLYBISTIN 1)
  • Enhancer of filmentation 1 (HEF1) (CRK-associated substrate-related protein) (CAS-L) (CasL) (PP105)
  • CASL HUMAN Neurogen expressed developmentally down-regulated 9
  • TXK HUMAN Tyrosine-protein kinase TXK (EC 2 7 1 112)
  • DJ862P8 3 (SIMILAR TO MAP3K10 (MITOGEN-ACTIVATED PROTEIN KINASE KINASEKINASE 10))
  • BCA1 HUMAN CRK-associated substrate p130Cas
  • p130Cas Breast cancer anti-estrogen resistance 1 protein
  • Tight junction protein ZO-2 (Zonula occludens 2 protein) (Zona occludens 2 protein) (Tight junction protein
  • NCK1 NCK adaptor protein 1
  • NCF4 HUMAN Neutrophil cytosol factor 4
  • NCF-4 Neutrophil NADPH oxidase factor 4
  • p40-phox p40phox
  • DLG2 HUMAN Channel associated protein of synapse-110 (Chapsyn-110) (Discs, large homolog 2)
  • Q8TC10 Hypothetical 78 2 kDa protein
  • DLG4 HUMAN Presynaptic density protein 95 (PSD-95) (Discs, large homolog 4)
  • ABL2 HUMAN Tyrosine-protein kinase ABL2 (EC 2 7 1 112) (Tyrosine kinase ARG)
  • DIHYDROPYRIDINE-SENSITIVE L-TYPE CALCIUM CHANNEL BETA-1-B1 SUBUNIT(BETA-1
  • Z03 HUMAN Tight junction protein ZO-3 (Zonula occludens 3 protein) (Zona occludens 3 protein) (Tight junction protein 3) FYB HUMAN FYN-binding protein (FYN-T-bindmg protein) (FYB-120/130) (p120/p130) (SLP-76 associated phosphoprotem) (SLAP-130) Q9BT70 UNKNOWN (PROTEIN FOR IMAGE 3628014) (FRAGMENT) GRAP HUMAN GRB2-related adaptor protein AAN07095 MEGAP transcript variant a Q13690 HYPOTHETICAL PROTEIN (FRAGMENT)
  • DJ823N20 1 1 V-SRC AVIAN SARCOMA (SCHMIDT-RUPPIN A-2) VIRAL ONCOGENE HOMOLOG (A
  • Hematopoietic lineage cell specific protein Hematopoietic cell- specific LYN substrate 1
  • LCKBP1 Hematopoietic cell- specific LYN substrate 1
  • Alpha-(1 ,6)-fucosyltransferase (EC 2 4 1 68) (Glycoprotein 6-alpha-L- fucosyltransferase) (GDP-fucose-
  • Mitogen-activated protein kinase kinase kinase 10 (EC 2 7 1 37) (Mixed lineage kinase 2) (Protein kinase
  • Thyroid receptor interacting protein 10 Thyroid receptor interacting protein 10
  • CAB2 Dihydropy ⁇ dine-sensitive L-type, calcium channel beta-2 subunit
  • CCB2 HUMAN channel beta-2 subunit (Lambert- Eaton myasthenic syndrome antigen B) (MYSB)
  • SSN1 HUMAN SAM-domain protein SAMSN-1 SAM domain, SH3 domain and nuclear localisation signals protein 1 )
  • MIA HUMAN Melanoma derived growth regulatory protein precursor Melanoma inhibitory activity
  • MPP2 HUMAN MAGUK P55 subfamily member 2 (MPP2 protein) (Discs, large homolog 2)
  • TRIO HUMAN Triple functional domain protein PPRF interacting protein
  • RIM1 HI IM ⁇ M YC B0X DEPENDENT INTERACTING PROTEIN 1 B0X DEPENDENT INTERACTING PROTEIN 1
  • BIDGING INTEGRATOR 1 AMPHIPHYSIN-LIKE PROTEIN
  • AMPHIPHYSIN II AMPHIPHYSIN II
  • BOX-DEPENDENT MYC- INTERACTING PROTEIN-1 CRK HUMAN Proto-oncogene C-crk (P38) (Adapter molecule crk)
  • Tyrosine-protein kinase ITK/TSK (EC 2 7 1 112) (T-cell-spe ⁇ fic kinase) (Tyrosine-protein kinase Lyk)
  • NCF-2 Neutrophil cytosol factor 2
  • NAF-2 Neutrophil NADPH oxidase factor 2
  • Protein kinase C and casein kinase substrate in neurons protein 3 (SH3 domain-containing protein 6511 )
  • Phosphatidylinositol 3-k ⁇ nase regulatory beta subunit (PI3-k ⁇ nase p85-beta subunit) (Ptdlns-3-k ⁇ nase p85-
  • Ras GTPase-activating protein 1 Ras GTPase-activating protein 1 (GTPase-activating protein) (GAP) (Ras p21 protein activator)
  • RSG1 HUMAN p120GAP
  • RasGAP RasGAP
  • JNK-interacting protein 2 JIP-2 (JNK MAP kinase
  • JIP2 HUMAN scaffold protein 2) (lslet-bra ⁇ n-2) (IB-2) (Mitogen-activated protein kinase 8- ⁇ nteract ⁇ ng protein 2)
  • IB-2 Mitogen-activated protein kinase 8- ⁇ nteract ⁇ ng protein 2
  • Intersectin 2 SH3 domain-containing protein 1 B
  • SH3P18 SH3P18-hke WASP associated protein
  • Tyrosine-protein kinase TEC (EC 2 7 1 112)
  • MAGUK P55 subfamily member 3 (MPP3 protein) (Discs, large homolog 3)
  • Tyrosine-protein kinase BTK (EC 2 7 1 112) (Bruton's tyrosine kinase) (Agammaglobuhnaemia tyrosine kinase) (ATK) (B cell progenitor kinase) (BPK)
  • HEFS Embryonal Fyn-associated substrate
  • CAB1 Dihydropy ⁇ dine-sensitive L-type, calcium channel beta-1 subunit (CAB1 ) (Voltage-dependent calcium channel beta-1 subunit)
  • LIM and SH3 domain protein 1 (LASP-1 ) (MLN 50)
  • Proto-oncogene tyrosine-protein kinase FGR (EC 2 7 1 112) (P55-FGR) (C-FGR)
  • SH3-conta ⁇ n ⁇ ng GRB2-l ⁇ ke protein 1 (SH3 domain protein 2B) (Extra eleven-nmeteen leukemia fusion SH31 HUMAN gene) (EEN) (EEN fusion partner of MLL) Q9H803 CDNA FLJ14023 FIS, CLONE HEMBA1003645, WEAKLY SIMILAR TO TIPD PROTEIN
  • SH3 adapter protein SPIN90 SH3 protein interacting with Nek, 90 kDa
  • SP90 HUMAN VIP54
  • AF3p21 Diaphanous protein interacting protein
  • DIP-1 Dia interacting prote ⁇ n-1
  • FRK HUMAN Tyrosine-protein kinase FRK (EC 2 7 1 112) (Nuclear tyrosine protein kinase RAK)
  • Phosphatidylinositol 3-k ⁇ nase regulatory alpha subunit (PI3-k ⁇ nase p85-alpha subunit) (Ptdlns-3-k ⁇ nase
  • DIHYDROPYRIDINE-SENSITIVE L-TYPE CALCIUM CHANNEL BETA-2 SUBUNIT(LAMBERT-EATON
  • CAB3 Dihydropyndine-sensitive L-type, calcium channel beta-3 subunit
  • Proto-oncogene tyrosine-protein kinase LCK (EC 2 7 1 112) (P56-LCK) (LSK) (T cell-specific protein-
  • NCF-1 Neutrophil cytosol factor 1
  • NADPH oxidase factor 1 (47 kDa neutrophil oxidase
  • NCF1 HUMAN factor p47-phox
  • NCF-47K 47 kDa autosomal chronic granulomatous disease protein
  • Proteins containing one or more PDZ domains Proteins containing one or more PDZ domains
  • Syntenin 1 (Syndecan binding protein 1) (Melanoma differentiation associated prote ⁇ n-9) (Mda-9) (Scaffold
  • SDB1 HUMAN protein Pbp1 (Pro-TGF-alpha cytoplasmic domain-interacting protein 18) (TACIP18)
  • DJ470B24 1 2 (MYELOID/LYMPHOID OR MIXED-LINEAGE LEUKEMIA (TRITHORAX(DROSOPHILA)
  • AAH38105 Similar to membrane protein, palmitoylated 3 (MAGUK p55 subfamily member 3)
  • Presynaptic protein SAP102 Synapse-associated protein 102
  • Neuroendoc ⁇ ne-DLG Neuroendoc ⁇ ne-DLG
  • NE-DLG Neuroendoc ⁇ ne-DLG
  • AAH23638 Membrane protein, palmitoylated 6 (MAGUK p55 subfamily member 6) Q8WXI1 CONNECTOR ENHANCER OF KSR2B PSD9 HUMAN 26S proteasome regulatory subunit p27 (26S proteasome non-ATPase subunit 9)
  • Amyloid beta A4 precursor protein-binding family A member 1 Neuron-specific X11 protein
  • DLG4 HUMAN Presynaptic density protein 95 (PSD-95) (Discs, large homolog 4)
  • Beta-1 -syntrophin 59 kDa dystrophin-associated protein A1 , basic component 1 (DAPA1 B) (Tax
  • E3KARP SOLUTE CARRIER FAMILY 9 ISOFORM A3 REGULATORY FACTOR 2
  • SJ2B HUMAN Synaptojanin 2 binding protein Mitochondrial outer membrane protein 25
  • PTN4 HUMAN Protein tvrosine ohosohatase non-receDtor tvoe 4 (EC 3 1 3 8 fProtein-tvrosine DhosDhatase MEG1 ⁇ (PTPase-MEG1) (MEG).
  • HRA2 HUMAN Serine protease HTRA2 (EC 3.4.21.-) (Omi stress-regulated endoprotease).
  • VELI 1 TX INTERACTION PROTEIN 33
  • FRAGMENT TAX INTERACTION PROTEIN 33
  • TKA-1 Q15599 TYROSINE KINASE ACTIVATOR PROTEIN 1
  • CARB HUMAN Caspase recruitment domain protein 11 (CARD-containing MAGUK protein 3) (Carma 1 ).
  • DLG2 HUMAN Channel associated protein of synapse-110 (Chapsyn-110) (Discs, large homolog 2).
  • pTN ⁇ . .... M PROTEIN TYROSINE PHOSPHATASE, NON-RECEPTOR TYPE 3 (EC 3.1.3.48)(PROTEIN-TYROSINE I J HUMAN PHOSPHATASE H1) (PTP-H1).
  • LIK2 HUMAN LIM domain kinase 2 (EC 2.7.1.-) (LIMK-2).
  • NEB1 HUMAN Neura ' Neuronal tissue-specific F-actin binding protein I
  • Protein phosphatase 1 regulatory subunit 9A Frragment
  • RIL HUMAN LIM protein RIL Reversion-induced LIM protein.
  • PDL1 HUMAN PDZ and LIM domain protein 1 LIM domain protein CLP-36) (C-terminal LIM domain protein 1) (Elfin)
  • Nitric-oxide synthase, brain (EC 1 14 13 39) (NOS, type I) (Neuronal NOS) (N-NOS) (nNOS) (Constitutive
  • N0S1 HUMAN NOS N0S1 HUMAN NOS
  • NC-NOS N0S1 HUMAN NOS
  • bNOS N0S1 HUMAN NOS
  • Protein tyrosine phosphatase, non-receptor type 13 (EC 3 1 3 48) (Protein-tyrosine phosphatase 1 E)
  • PTND HUMAN PPP-E1 (hPTPEI )
  • PPP-BAS Protein-tyrosine phosphatase PTPL1 (Fas-associated protein-tyrosine phosphatase 1 ) (FAP-1 )
  • MPP3 HUMAN MAGUK P55 subfamily member 3 (MPP3 protein) (Discs, large homolog 3)
  • LIK1 HUMAN LIM domain kinase 1 (EC 2 7 1 37) (LIMK-1)
  • IL16 HUMAN lnterleuk ⁇ n-16 precursor (IL-16) (Lymphocyte chemoattractant factor) (LCF)
  • AAH39612 Similar to TGF-beta1- ⁇ nduced anti-apoptotic factor 1
  • Amyloid beta A4 precursor protein-binding family A member 2 Neuron-specific X11L protein
  • APB2 HUMAN Mund 8-1 -interacting protein 2) (M ⁇ nt-2) (Adapter protein X11 beta)
  • DJ470B24 1 1 (MYELOID/LYMPHOID OR MIXED-LINEAGE LEUKEMIA (TRITHORAX(DROSOPHILA)
  • PIC1 HUMAN PRKCA-binding protein Protein kinase C-alpha binding protein
  • PIC1 HUMAN PRKCA-binding protein Protein kinase C-alpha binding protein
  • PIC1 HUMAN PRKCA-binding protein Protein kinase C-alpha binding protein
  • Amyloid beta A4 precursor protein-binding family A member 3 Neuron-specific X11L2 protein
  • APB3 HUMAN Mund 8-1 -interacting protein 3 (M ⁇ nt-3) (Adapter protein X11gamma)
  • Tight junction protein ZO-2 (Zonula occludens 2 protein) (Zona occludens 2 protein) (Tight junction protein
  • Tight junction protein ZO-3 (Zonula occludens 3 protein) (Zona occludens 3 protein) (Tight junction protein
  • Alpha-1 -syntrophin 59 kDa dystrophin-associated protein A1 , acidic component 1 ) (Pro-TGF-alpha
  • APICAL-LIKE PROTEIN APICAL-LIKE PROTEIN
  • SH3 and multiple ankynn repeat domains protein 1 (Shankl) (Somatostatin receptor interacting protein)
  • SHK1 HUMAN SSTR interacting protein
  • Tight junction protein ZO-1 (Zonula occludens 1 protein) (Zona occludens 1 protein) (Tight junction protein

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
  • Urology & Nephrology (AREA)
  • Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Cell Biology (AREA)
  • Medicinal Chemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Biotechnology (AREA)
  • Food Science & Technology (AREA)
  • Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Endocrinology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Toxicology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention concerne un processus de mise au point de médicaments, qui permet d'identifier un ligand pouvant se lier à une molécule cible biologique. Le processus consiste à: a) produire un complexe de transduction de signal comprenant une molécule cible biologique, une ou plusieurs molécule(s) effectrice(s) aval et, éventuellement, une protéine adaptatrice; b) placer le ligand au contact du complexe de transduction de signal; et c) mesurer un éventuel effet résultant du processus de transduction de signal, qui se rapporte à la molécule cible biologique et à une ou plusieurs molécule(s) effectrice(s) aval. L'invention concerne un processus de mise au point de médicaments dans lequel le complexe de transduction de signal comprend un premier élément contenant une molécule cible biologique; un deuxième élément contenant une ou plusieurs protéine(s) adaptatrice(s); et un troisième élément contenant une ou plusieurs molécule(s) effectrice(s) aval. Chaque élément reconnaît ou se lie à au moins un des autres éléments pour accomplir un processus de transduction de signal. Au moins un des éléments a été modifié de manière à contenir un ou plusieurs domaine(s) et/ou un ou plusieurs motif(s) de reconnaissance.
PCT/DK2002/000901 2001-12-21 2002-12-20 Utilisation d'un complexe de transduction de signal dans des processus de mise au point de medicaments Ceased WO2003056329A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2002357449A AU2002357449A1 (en) 2001-12-21 2002-12-20 Use of a signal transduction complex in drug discovery processes

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DKPA200101944 2001-12-21
DKPA200101944 2001-12-21

Publications (2)

Publication Number Publication Date
WO2003056329A2 true WO2003056329A2 (fr) 2003-07-10
WO2003056329A3 WO2003056329A3 (fr) 2003-11-27

Family

ID=8160930

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DK2002/000901 Ceased WO2003056329A2 (fr) 2001-12-21 2002-12-20 Utilisation d'un complexe de transduction de signal dans des processus de mise au point de medicaments

Country Status (2)

Country Link
AU (1) AU2002357449A1 (fr)
WO (1) WO2003056329A2 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010151747A1 (fr) * 2009-06-26 2010-12-29 Cystic Fibrosis Foundation Therapeutics, Inc. Composés de pyramine ainsi que leurs procédés de fabrication et d'utilisation
US8334292B1 (en) 2010-06-14 2012-12-18 Cystic Fibrosis Foundation Therapeutics, Inc. Pyrimidine compounds and methods of making and using same
US8513242B2 (en) 2008-12-12 2013-08-20 Cystic Fibrosis Foundation Therapeutics, Inc. Pyrimidine compounds and methods of making and using same

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RS53827B1 (sr) 2009-11-02 2015-06-30 Pfizer Inc. Derivati dioksa-biciklo[3.2.1]oktan-2,3,4-triola

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002523056A (ja) * 1998-08-18 2002-07-30 ザ ジョンズ ホプキンス ユニバーシティー スクール オブ メディシン Ｈｏｍｅｒ相互作用タンパク質
DE19860833C1 (de) * 1998-12-30 2000-09-07 Albrecht E Sippel Methode zur zellulären High-Throughput(Hochdurchsatz)-Detektion von Rezeptor-Liganden-Interaktionen

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8513242B2 (en) 2008-12-12 2013-08-20 Cystic Fibrosis Foundation Therapeutics, Inc. Pyrimidine compounds and methods of making and using same
WO2010151747A1 (fr) * 2009-06-26 2010-12-29 Cystic Fibrosis Foundation Therapeutics, Inc. Composés de pyramine ainsi que leurs procédés de fabrication et d'utilisation
US8334292B1 (en) 2010-06-14 2012-12-18 Cystic Fibrosis Foundation Therapeutics, Inc. Pyrimidine compounds and methods of making and using same

Also Published As

Publication number Publication date
WO2003056329A3 (fr) 2003-11-27
AU2002357449A1 (en) 2003-07-15
AU2002357449A8 (en) 2003-07-15

Similar Documents

Publication Publication Date Title
Dey et al. DNA–protein interactions: methods for detection and analysis
Terstappen et al. Target deconvolution strategies in drug discovery
Hughes Yeast and drug discovery
Bockaert et al. The ‘magic tail’of G protein-coupled receptors: an anchorage for functional protein networks
JP5415264B2 (ja) 検出可能な核酸タグ
Hu et al. Functional protein microarray technology
O'Day CaMBOT: profiling and characterizing calmodulin-binding proteins
Hasegawa et al. Distinct roles for Khd1p in the localization and expression of bud-localized mRNAs in yeast
Kay et al. Convergent evolution with combinatorial peptides
EP1628994A2 (fr) Procede d'identification de modulateurs de la signalisation de recepteur couple a une proteine g
AU2008229749A1 (en) Novel compositions and methods for cancer
Dimitrova-Paternoga et al. Validation and classification of RNA binding proteins identified by mRNA interactome capture
EP1502102A2 (fr) Composes et procedes pour analyser le proteome
CN110418801A (zh) 鉴定恶臭调节化合物的方法
Lenfant et al. A genome-wide study of PDZ-domain interactions in C. elegans reveals a high frequency of non-canonical binding
CA2381699A1 (fr) Nouvelles techniques de diagnostic de l'angiogenese, compositions et techniques de criblage pour modulateurs d'angiogenese
Sharma et al. Localization of RNAs to the mitochondria—mechanisms and functions
Davey G-protein-coupled receptors: new approaches to maximise the impact of GPCRS in drug discovery
Palmer et al. Identification and characterisation of human apoptosis inducing proteins using cell-based transfection microarrays and expression analysis
Janssen et al. Interaction partners for human ZNF384/CIZ/NMP4—zyxin as a mediator for p130CAS signaling?
EP1509539A2 (fr) Compositions et procedes concernant le cancer
WO2003055914A2 (fr) Recepteurs modifies pour la recherche de ligands therapeutiques
WO2005116265A2 (fr) Ensembles de sondes permettant l'etablissement de profils d'expressions pour les genes de rats
WO2003056329A2 (fr) Utilisation d'un complexe de transduction de signal dans des processus de mise au point de medicaments
McPherson et al. Peptide motifs: building the clathrin machinery

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SC SD SE SG SK SL TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR IE IT LU MC NL PT SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

WWW Wipo information: withdrawn in national office

Country of ref document: JP