Mar2007 Drug Protein Targets
CD47 molecule
CD47 is a membrane protein associated with integrins β1 and β2. It serves as a receptor for both thrombospondin (TSP) and a ligand for the transmembrane signal regulatory protein, SIRP. It is involved in the platelet activation, cell motility, leucocyte adhesion, migration and phagocytosis. CD47 also functions as a marker of self on murine red blood cells and its expression is reduced in expression on Rh erythrocytes. It rapidly induces cell death in T-cells and chronic lymphocytic leukaemic B-cells in a caspase-independent
- Chugai is developing a monoclonal disulfidestabilized dimer of a single chain antibody against CD47 for the treatment of chronic lymphocytic leukaemia (CLL) and other lymphoid malignancies.
- The Entrez Gene ID for CD47 molecule is 961.
complement component C3
Complement component C3 is a protease involved in both the acquired and innate immune response, and its activation is required for both classical and alternative complement activation pathways. It has been found that deposition of complement components C3 and C5 in early subretinal pigmented epithelium occurs in both patients with age-related macular degeneration (AMD) and in mouse models of AMD.
- POT-4 is a derivative of the cyclic peptide compstatin that binds to the complement factor C3, under development by Potentia Pharmaceuticals for wet and dry AMD.
- Its Entrez Gene ID is 718.
CD83 molecule
CD83 is a glycoprotein expressed on the cell surface of mature dendritic cells (DCs), which are potent stimulators of immune responses. Its expression is upregulated during DC maturation which suggests that it plays an important functional role in the induction of immune responses.
- Argos Therapeutics is developing a soluble form of CD83 as an immunosuppressant.
- The Entrez Gene ID for CD83 is 9308.
dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 3
Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 3 (DYRK3) catalyzes autophosphorylation on serine/threonine and tyrosine residues. DYRK3 has been shown to catalyze phosphorylation of histones H3 and H2B in vitro. It plays a role in the growth and survival of blood cells.
- 626616 is a small-molecule DYRK3 antagonist, under development by GlaxoSmithKline for anaemia and as a chemprotective.
- The Entrez Gene ID for DYRK3 is 8444.
- DYRK3 belongs to the Enzyme > Kinase Target Family Group, and its EC number is 2.7.12.1
germ cell associated 2 (haspin)
The haspin gene encodes a 798-amino-acid protein, which contains an N-terminal basic region, a C-terminal leucine zipper and a protein kinase domain in addition to several phosphorylation sites. It is required for mitotic histone H3 Thr 3 phosphorylation and normal metaphase chromosome alignment.
- SuperGen is developing a haspin inhibitor as an anticancer.
- The Entrez Gene ID for haspin is 83903.
histone deacetylase 6
Histone deacetylase 6 (HDAC6) belongs to the class II of the histone deacetylase/acuc/apha family. It is localized exclusively in the cytoplasm, where it associates with microtubules and accumulates with the microtubule motor complex. Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events and so acetylation/deacetylation of histones alter chromosome structure and affect transcription factor access to DNA.
- St Bartholomew's Hospital and University College London, both London, the UK, are developing a HDAC6 inhibitor, UCL-67022 as an anticancer.
- The Entrez Gene ID for HDAC6 is 10013.
- HDAC6 belongs to the Enzyme Target Family Group.
interleukin 1, alpha
Interleukin 1 alpha is a pleiotropic cytokine involved in various immune responses, inflammatory processes, and haematopoiesis. It is produced by monocytes and macrophages as a proprotein, which is proteolytically processed and released in response to cell injury, and thus induces apoptosis.
- Cytos Biotechnology is developing IL-1aQb, an IL-1α-based vaccine for the treatment of atherosclerosis.
- Its Entrez Gene ID is 3552.
melanoma antigen family A, 4
Melanoma antigen family A, 4 (MAGEA4) directs the expression of tumor antigens recognized on human melanomas by autologous cytolytic T-lymphocytes. It is expressed in several tumour cell types but is silent in normal tissues, with the exception of male germline cells that do not express HLA.
- ImmunoFrontier is developing a vaccine against MAGEA4 for the treatment of nsclc.
- The Entrez Gene ID for MAGEA4 is 4103.
NOL1/NOP2/Sun domain family, member 2
NOL1/NOP2/Sun domain family, member 2, also known as MISU, methylates RNA polymerase III transcripts. It mediates Myc-induced keratinocyte cell proliferation and growth. It is expressed at low levels in normal tissue and becomes upregulated in certain cancers.
- Cancer Research Technology is developing a compound against MISU for the treatment of Myc-associated cancers.
- Its Entrez Gene ID is 54888.
transient receptor potential cation channel, subfamily V, member 4
The transient receptor potential cation channel, subfamily V, member 4 (TRPV4) is a member of the vanilloid subfamily of ion channels and is a calcium-permeable, nonselective cation channel that is thought to be involved in the regulation of systemic osmotic pressure. TRPV4 is proposed to function as a transducer of hypotonic stimuli in primary afferent nociceptive neurons and to contribute to inflammatory and neuropathic pain.
- Renovis is developing a TRPV4 antagonist for the treatment of chronic pain.
- The Entrez Gene ID for TRPV4 is 59341.
- TRPV4 belongs to the Ion Channel >Transient receptor potential channel Target Family Group.
tumour-associated calcium signal transducer 2
Tumour-associated calcium signal transducer 2, also known as TROP2, is an intronless gene encoding a carcinoma-associated antigen defined by the monoclonal antibody GA733. This antigen transduces an intracellular calcium signal and acts as a cell surface receptor.
- ARIUS Research is developing AR-47A6.4.2, a humanized antibody identified using its FunctionFIRST platform for the treatment of pancreatic cancer.
- The Entrez Gene ID for TROP2 is 4070.
