Jan2007 Drug Protein Targets
Aurora kinase C
5-hydroxytryptamine (serotonin) receptor 5A (5- HT5A)
5-HT5A is a member of the serotonin receptor family and is implicated in various psychiatric conditions; it also has vasoactive effects. It is expressed solely in the central nervous system.
- Abbott is developing 5-HT5A antagonists for the treatment of CNS disorders. They have potential in schizophrenia, bipolar disorders, autism, migraine and pain.
- 5-HT5A belongs to the Receptor > GPCR > 5- hydroxytryptamine Target Family Group.
- Its Entrez Gene ID is 3361
Acid phosphatase, prostate (PAP)
PAP is a glycoprotein responsible for catalyzing the conversion of orthophosphoric monoester to alcohol and orthophosphate. It is synthesized in the epithelial cells of the prostate gland and secreted into the prostate fluid.
- BN ImmunoTherapeutics (Bavarian Nordic) is developing an MVA-BN prostate cancer vaccine. It expresses sequences that direct immunity to PSA and PAP.
- PAP belongs to the Enzyme Target Family Group . Its EC number is 3.1.3.2.
- Its Entrez Gene ID is 55.
aldehyde dehydrogenase 2 family (mitochondrial)
Aldehyde dehydrogenase 2 family (mitochondrial) (ALDH2) is the second enzyme of the major oxidative pathway of alcohol metabolism. There are two major liver isolforms of ALDH: ALDH1, the liver isoform; and ALDH2, the mitochondrial isoform that is localized in the mitochondrial matrix. Most Caucasians have both the major isozymes, where as about 50% of Orientals only have ALDH1, and are missing ALDH2. Absence of ALDH2 could be related to a remarkably higher frequency of acute alcohol intoxication among Orientals compared to Caucasians.
- CV Therapeutics is developing an ALDH2 antagonist for the treatment of alcohol dependence.
- The Entrez Gene ID for ALDH2 is 217.
- ALDH2 belongs to the Enzyme>Dehydrogenase Target Family Group. Its EC number is 1.2.1.3
Aurora kinase C belongs to the Aurora subfamily of serine/threonine kinases and acts as a chromosomal passenger protein that forms complexes with aurora b and inner centromere proteins. It is thought to play a role in microtubule organization during mitosis. Its overexpression in several cancer lines suggests its role in oncogenic signal transduction.
- Amphora is developing inhibitors of aurora kinases a, b and c for the treatment of solid tumours.
- Aurora kinase C belongs to the Enzyme > Kinase Target Family Group.
- Its Entrez Gene ID is 6795.
AXL receptor tyrosine kinase
AXL is a unique tyrosine kinase receptor, implicated in the inhibition of apoptosis. Its substrate is Gas6. It is a chronic myelogenous leukemia-associated oncogene and is also associated with colon cancer and melanoma. Overexpression of Axl in myeloid cells has shown to be involved in Type II diabetes.
- SuperGen is developing AXL kinase inhibitors, using its CLIMB technology for the treatment of cancer.
- AXL receptor tyrosine kinase belongs to the Enzyme > Kinase and Receptor Target Family Groups. Its EC number is 2.7.10.1.
- Its Entrez Gene ID is 558.
dihydropyrimidinase-like 2 (CRMP-2)
CRMP-2 is a member of the collapsin response mediator proteins, which regulate neurite outgrowth.
- Schwarz Pharma is developing lacosamide, an amino acid that modulates CRMP-2 and enhances slow inactivation of voltage-gated sodium channels for the treatment of epilepsy and neuropathic pain.
- CRMP-2 belongs to the Enzyme Target Family Group.
- Its Entrez Gene ID is 1808.
hemochromatosis type 2 (juvenile) (HJV)
HJV is a protein expressed only in the heart, skeletal muscle and the liver. It is thought to be involved in the regulation and availability of red blood cell production and has been found to be the defective protein in the hereditary disorder juvenile haemochromatosis.
- Xenon, in collaboration with Roche, is developing haemojuvelin inhibitors for the treatment of anaemia of inflammation, an acquired condition associated with infections, cancer and inflammatory conditions such as arthritis.
- Its Entrez Gene ID is 148738.
lectin, galactoside-binding, soluble, 1 (galectin-1)
Galectin-1 is a member of the β-galactosidase-binding protein which is involved in modulating cell-cell and cellmatrix interactions. It is the receptor for anginex, an angiogenisis inhibitor. It is overexpressed in endothelial cells of different human tumors.
- Unibioscreen is developing UNBS-1070, a galectin- 1 inhibitor for the treatment of cancer.
- Galectin-1 belongs to the Peptide hormone and Receptor Target Family Groups.
- Its Entrez Gene ID is 3956
leucine-rich repeat kinase 2
Leucine-rich repeat kinase 2 (LRRK2) is predominanly expressed in the cytoplasm but also associates with the mitochondrial outer membrane. Mutations in this gene have been associated with autosomal-dominant Parkinsonism with clinical features of Parkinson's disease.
- Wyeth is developing LRRK2 inhibitors for the treatment of Parkinson's disease.
- The Entrez Gene ID LRRK2 is 120892.
Low density lipoprotein-related protein 2 (megalin)
Megalin is part of the Heymann nephritis antigenic complex with RAP. It is expressed in specialized epithelia including in the inner ear neural tube, lung airway, epididymis, yolk sac, glomeruli, and proximal renal tubules.
- ReceptIcon is developing two megalin antagonists for the protection against aminoglycosidemediated nephrotoxity and for the treatment of steroid dependant cancer, respectively.
- Megalin belongs to the Receptor Target Family Group.
- Its Entrez Gene ID is 4036
Peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC1A)
PGC1A is a transcriptional coactivator that interacts with PPAR gamma to allow interaction of this protein with multiple transcription factors and regulation of genes involved in energy metabolism.
- Sirtris is developing SRT-501, a formulation of resveratrol, which activates PGC1A and SIRT1, for the treatment of Huntington's diseases and Type II diabetes.
- PGC1A's Entrez Gene ID is 10891.
Prokineticin receptor 1 and prokineticin 1
Both prokineticin-1 and its receptor are important in the control of GI motility. Prokineticin 1 (EG-VEGF)'s expression is complementary to VEGF. It is induced by hypoxia and restricted to the steroidogenic glands (ovary, testis, adrenal, and placenta).
- Kinexis is developing drugs that target prokineticins including prokineticin-1 and prokineticin-2.
- Prokineticin receptor 1 belongs to the Receptor > GPCR > Neuropeptide Y Target Family Group -
- Its Entrez Gene ID is 10887.
- Prokineticin 1 belongs to the Cytokine/Growth Factor > Growth Factor Target Family Group -
- Its Entrez Gene ID is 84432.
Pim-1 oncogene
Pim-1 is a protooncogene known to be involved as a downstream effector in a number of cytokine signalling pathways. Its active form causes progression of the cell cycle and inhibition of apoptosis. Expression of pim-1 is seen in cells of haemopioetic origin, such as thymus, bone marrow and foetal liver cells.
- SuperGen is developing a series of pim-1 kinase inhibitors for the treatment of cancer, using its CLIMB drug discovery process.
- Its Entrez Gene ID is 5292.
- Pim-1 belongs to the Enzyme > Kinase Target Family Group.
Preferentially expressed antigen in melanoma (PRAME)
PRAME is an antigen, highly expressed in various solid tumours and in normal testis. It is recognized by cytotoxic T-lymphocytes.
- MKC-1106-PP is an immunotherapy, under development by Mannkind for the treatment of solid tumours. It targets tumour-related antigens, including PRAME, to induce a cell-mediated immune response. It is injected straight into the lymph nodes to achieve high local concentrations.
- PRAME's Entrez Gene ID is 23532.
PTK7 protein tyrosine kinase 7
PTK7 is a member of the subgroup of protein tyrosine kinases that lack detectable catalytic tyrosine kinase activity but retain roles in signal transduction. It is expressed in colon carcinomas but not in normal colons and may therefore be involved in or act as a marker for tumour progression.
- Medarex is developing an anti-Ptk7 MAb for the treatment of cancer.
- The Entrez Gene ID for PTK7 is 5754.
- It belongs to the Kinase Target Family Group. Its EC number is 2.7.10.1
Superoxide dismutase 2, mitochondrial
More commonly known as sulfamidase, this is the enzyme deficient in Sanfilippo syndrome A, or mucopolysaccharidosis IIIA, a lysosomal storage disease. It is an enzyme of the hydrolase class that catalyzes the cleavage of sulfate groups from the amino groups of sulphated glucosamine residues.
- Shire Human Genetic Therapies (Shire) is developing a recombinant sulfamidase (heparin- N-sulfatase) enzyme for the treatment of Sanfilippo syndrome. It is delivered intrathecally.
- Sulfamidase belongs to the Enzyme Target Family Group. Its EC number is 3.10.1.1.
- Its Entrez Gene ID is 6648.
Torsin family 1, member A (torsin A)
Torsin A is a member of the ATPase target family. It is predominantly expressed in the substantia nigra pars compacta. Mutations in this gene result in the autosomal dominant disorder, torsin dystonia 1, a movement disorder characterized by twisting muscle contractures.
- Alnylam is developing siRNAs designed to inhibit both human wt and mutant torsin A for the treatment of torsin dystonia.
- Torsin A belongs to the Enzyme > protease/ peptidase Target Family Group.
- Its Entrez Gene ID is 1861.
Tumour suppressor candidate 4
Tumour suppressor candidate 4, also known as NPRL2, is a tumour suppressor gene, deletions of which are associated with lung, breast, pancreatic, oral and uterine cancers.
- Introgen Therapeutics is developing NPRL2 nanoparticles for the treatment of cancer.
- NPRL2's Entrez Gene ID is 10641.
V-set domain containing T-cell activation inhibitor 1
This costimulatory ligand of the B7 superfamily is also known as B7H4, and is expressed on the surface of antigen-presenting cells. It functions as a negative regulator of T-cell responses. B7H4 is expression is high in ovarian and breast cancers but is relatively low in normal tissues.
- Medarex is developing an anti-B7H4 MAb for the treatment of cancer.
- The Entrez Gene ID is 79679.
Zona pellucida glycoprotein 3 (sperm receptor)(ZP3)
The ZP3 protein is a structural component of the zona pellucidia. It plays a key role in the induction of the acrisome reaction in the first step of fertilization. ZP3 is overexpressed in cancers.
- Genmab is developing HuMax-ZP3, a fully-human MAb against ZP3 for the treatment of cancer.
- ZP3 belongs to the Receptor Target Family Group.
- Its Entrez Gene ID is 7784.
