Oct2006 Drug Protein Targets
mannosidase, alpha, class 2B, member 1
Also known as lysosomal alpha-mannosidase (MAN2B1), this is the enzyme that cleaves alpha-mannosidic linkages from the non-reducing end of N-linked glycoproteins. It is a member of family 38 glycosyl hydrolases. Defects in this gene causes alphamannosidosis, a lysosomal storage disease characterized by the accumulation of mannose-rich oligosaccharides.
- Zymex is developing M-0011, a recombinant lysosomal acid Α-mannosidase for the treatment of Α-mannosidosis.
- The Entrez Gene ID for MAN2B1 is 4125.
arylsulfatase A (ARSA)
This protein hydrolyzes cerebroside sulfate to cerebroside and sulfate. Defects in this gene lead to metachromatic leukodystrophy (MLD), one of several lipid storage diseases, which result in the toxic build-up of lipids in cells in the nervous system, liver, and kidneys.
- Zymex is developing a recombinant ARSA lysosomal enzyme for the treatment of MLD.
- The Entrez Gene ID for ARSA is 410.
hepatitis A virus cellular receptor 1
Abbreviated to HAVCR1, this is a type I transmembrane protein and member of the T-cell Ig and mucin domain (Tim) family of proteins, which has been implicated in the control of T-cell-mediated immune responses. High expression of HAVCR1 has been demonstrated in ovarian and renal cell carcinoma (RCC) cell lines.
- CR-014-vcMMAE is a fully-human MAb-drug conjugate targeting HAVCR1, under development by CuraGen for the treatment of RCC and ovarian cancer.
- The Entrez Gene ID for HAVCR1 is 26762.
calcium channel, voltage-dependent, alpha 1F subunit
The alpha 1F subunit of the voltage-dependent calcium channel (CACNA1F) is a member of the alpha-1 subunit family which has 24 pore-forming transmembrane segments. In atrial fibrillation, the atrial electrical activity is very rapid (approximately 400 to 700 beats/min), but as each impulse results in the depolarization of only a small islet of atrial myocardium, the atria as a whole does not contract. Calcium inhibitors block calcium channels in the heart, thus slowing down the electrical activity in the heart.
- Astellas is developing YM-758, an orally-active cardiac 1f channel inhibitor for the treatment of atrial fibrillation and stable angina.
- The Entrez Gene ID for CACNA1F is 778.
collagen, type IV, alpha 3 (Goodpastures antigen) binding protein
More commonly known as GPBP (Goodpasture antigen binding protein), this is a kinase that phosphorylates the N-terminal region of the Goodpasture antigen. An autoimmune response directed at this antigen causes Goodpasture disease, characterized by a rapid glomerulonephritis and often lung haemorrhage.
- NephroGenex is developing inhibitors of the GPBP kinase, for the treatment of glomerulosclerosis.
- The Entrez Gene ID for GPBP is 10087.
