Apr2007 Drug Protein Targets
coagulation factor V (proaccelerin, labile factor)
Coagulation factor V is an essential factor in the blood coagulation cascade. This factor circulates in plasma, and is converted to the active form by the release of the activation peptide by thrombin during coagulation.
- Crucell is developing a recombinant Factor V molecule expressed in its proprietary PER.C6 cell line, for treatment of haemophilia A.
- Factor V belongs to the Enzyme Target Family.
- Its Entrez Gene ID is 2153.
cysteinyl leucotriene receptor 2
Cysteinyl leucotriene receptor 2 (CysLTR2) encodes a 7-transmembrane protein that is one of two receptors activated by proinflammatory cysteinyl leucotrienes such as LTC4 and LTD4. It has been shown to modulate endothelial permeability, with a suggested role in cardiovascular and endocrine systems.
- AM-103 is an inhibitor of CysLTR1, -2 and BLT1, under development by Amira Pharmaceuticals.
- CysLTR2 is a member of Receptor > GPCR > Leucotreine Target Family Group.
- Its Entrez Gene ID is 57105.
EPH receptor A1
EPH receptor A1 (EPHA1) belongs to the ephrin receptor subfamily of the receptor protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. EPHA1 is expressed in some human cancer cell lines, and has been implicated in carcinogenesis.
- EPHA1 belongs to the Receptor and Enzyme>Kinase Target Families and its EC number is 2.7.10.1.
- Its Entrez Gene ID for CRM1 is 2041.
exportin 1 (CRM1 homologue, yeast)
Exportin 1 is a nuclear protein essential for proliferation and chromosomal region maintenance. It mediates leucine-rich nuclear export signal (NES)-dependent protein transport and specifically inhibits the nuclear export of Rev and U snRNAs and important 'cargo' proteins associated with oncogenesis such as p53, BCR-Abl and FOXO-3a. It is also involved in the control of several cellular processes via the control of the localization of cyclin B, MPAK, and MAPKAP kinase 2. This protein also regulates NFAT and AP-1.
- KOS-2385 and KOS-1815 are analogues of the natural polyketide leptomycin B and leads in a series of nuclear export inhibitors that target CRM1, under development by Kosan Biosciences for the treatment of cancer.
- Its Entrez Gene ID for CRM1 is 7514.
glycerol-3-phosphate acyltransferase, mitochondrial
Two main mamalian isoforms of glycerol-3-phosphate acyltransferase (GPAT) have been identified, on the basis of localization to the endoplasmic reticulum or the mitochondria. The mitochondrial isoform, abbreviated to GPAM or GPAT1, is found on the outer membrane and catalyzes the first step of glycerolipid biosynthesis using saturated fatty acy-CoA as a substrate to regulate cellular levels of triacylgerol and phospholipids.
- FAS-115 is a GPAT inhibitor in a series of antiobesity compounds under development by FASgen.
- GPAM belongs to the Enzyme > Transferase Target Family Group and its EC number is 2.3.1.15.
- Its Entrez Gene ID is 57678.
G protein-coupled receptor 109A
G protein-coupled receptor 109A (GPR109A), is a member of the class I rhodopsin GPCRs and is a receptor for nicotinic acid, which shares 96% identity with GPR109B. Its expression is highest in adipose tissue. It has been found to mediate both cAMP-dependant fatty acid decrease and PGD2-induced flushing.
- Arena is developing GPR109 receptor agonists for the treatment of atherosclerosis.
- GPR109A belongs to the Receptor > GPCR Target Family Group. Its Entrez Gene ID is 338442.
high mobility group AT-hook 1
High mobility group AT-hook 1 (HMGA1) is a non-histone protein involved in many cellular processes, including regulation of inducible gene transcription, integration of retroviruses into chromosomes, and the metastatic progression of cancer cells. It preferentially binds to the minor groove of A+T-rich regions in double-stranded DNA and is frequently acetylated and is found in the nucleus. At least seven transcript variants encoding two different isoforms (a and b) have been found for this gene.
- NOX-A50 is a spiegelmer against the isoform b of the transcription factor HMGA1, under development by Noxxon Pharma for the treatment of cancer.
- The Entrez Gene ID for HMGA1 is 3159.
inducible T-cell co-stimulator
Inducible T-cell co-stimulator, also known as ICOS, belongs to the CD28 and CTLA-4 cell-surface receptor family. It forms homodimers and plays an important role in the production of both type 1 and type 2 cytokines by recently activated T-cells, cell-cell signaling, immune responses, and regulation of cell proliferation.
- MedImmune is developing an anti-ICOS MAb for the treatment of inflammatory diseases.
- The Entrez Gene ID for ICOS is 29851.
low density lipoprotein-related protein 1 (alpha-2-macroglobulin receptor)
Low density lipoprotein-related protein 1 (alpha-2-macroglobulin receptor) - also known as LRP1 - is a multifunctional cell surface receptor that has been shown to bind a variety of ligands. It is primarily located on hepatocytes and has been found to be overexpressed in hepatocellular carcinoma (HCC), with continued overexpression in metastasized HCC and underexpressed on non-cancerous cirrhotic hepatocytes.
- Raptor is developing HepTide, a receptor-associated protein (RAP)-based peptide targeting LRP1 that is conjugated to a chemotherapeutic for use as a radio/chemosensitizer.
- LRP1 belongs to the Receptor Target FamilyGroup.
- Its Entrez Gene ID is 4035.
v-akt murine thymoma viral oncogene homologue 3 (protein kinase B, gamma)
Known by its official symbol AKT3, this is a member of serine/threonine protein kinases called AKTs or PKBs, which regulate cell signalling in response to insulin and growth factors. AKTs have been shown to be an element of the cell survival pathway and are therefore involved in a wide variety of biological processes, including cell proliferation, differentiation, apoptosis and tumorigenesis. ATK3 has been specifically shown to be stimulated by platelet-derived growth factor (PDGF), insulin, and insulin-like growth factor 1 (IGF1).
- GSK-690693 is a pan-AKT inhibitor under development by GlaxoSmithKline for the treatment of cancer.
- AKT3 belongs to the Enzyme > Kinase Target Family Group.
- Its Entrez Gene ID is 10000.
