Becaplermin, Recombinant Human PDGFB

Specification

• Cat#: THP-0184
• Product Name: Becaplermin, Recombinant Human PDGFB
• Description: The product is produced by recombinant DNA technology by insertion of the gene for the B chain of platelet derived growth factor (PDGF) into the yeast, Saccharomyces cerevisiae. The product has a molecular weight of approximately 25 KD and is a homodimer composed of two identical polypeptide chains that are bound together by disulfide bonds.
• Sequences: SLGSLTIAEPAMIAECKTRTEVFEISRRLIDRTNANFLVWPPCVEVQRCSGCCNNRNVQCRPTQVQLRPVQVRKIEIVRKKPIFKKATVTLEDHLACKCETVAAARPVT
• Species: Human
• Molecular Weight: 12294.4 Da
• Source: Yeast
• Purity: >99% by SDS-Page and HPLC analysis
• Cas No: 165101-51-9
• Formula: C532H892N162O153S9
• Endotoxin Level: <0.001 EU per 1 μg of the peptide by the LAL method
• Biological Activity: 100 ug/1g
• Storage: Lyophilized protein should be stored at < -20°C, though stable at room temperature for 3 weeks. Reconstituted protein solution can be stored at 2-8 °C for 1 week. Aliquots of reconstituted samples are stable at < -20°C for 3 months.

Pharmaceutical Information

• Pharmaceutical Application: Becaplermin
• Applications: For topical treatment of skin ulcers (from diabetes).
• Examples of Clinical Use: skin ulcers (from diabetes)
• Pharmacodynamics: Binds to the beta platelet-derived growth factor (PDGF) receptor, a tyrosine kinase receptor. PDGF is known to exist as a dimer, and activates its signaling pathway by a ligand induced receptor dimerization and autophosphorylation. PDGF receptors also contain many auto-phosphorylation sites, which serve to mediate binding of SH2 sites and subsequently signal corresponding pathways. There are five different isoforms of PDGF that activate through two different receptors (alpha and beta).
• Mechanism of action: Binds to the beta platelet-derived growth factor (PDGF) receptor, a tyrosine kinase receptor. PDGF is known to exist as a dimer, and activates its signaling pathway by a ligand induced receptor dimerization and autophosphorylation. PDGF receptors also contain many auto-phosphorylation sites, which serve to mediate binding of SH2 sites and subsequently signal corresponding pathways. There are five different isoforms of PDGF that activate through two different receptors (alpha and beta).
• Affected organisms: Humans and other mammals
• Targets: Target 1. Platelet-derived growth factor receptor beta; Target 2. Platelet-derived growth factor receptor alpha; Target 3. Alpha-2-macroglobulin

Related Reading

Background of PDGFB

Platelet-derived growth factor B, commonly known as PDGFB, plays an important role in various biological processes and its dysregulation has been associated with several pathological conditions.

The PDGFB gene was first discovered in the early 1980s as a secreted homodimer that functions as a potent mitogen for cells of mesenchymal origin. The gene for PDGFB is located on chromosome 22q13.1, comprises of 7 exons and spans around 35k bases in the human genome. The translated protein has a molecular mass of 24.4 kDa and possesses a cystine-knot motif, a characteristic structure in the growth factor family of proteins.

PDGFB protein function

A key function of the PDGFB protein is to regulate cell growth and division. More importantly, it assists in angiogenesis by controlling the migration and proliferation of vascular smooth muscle cells, which are integral to the formation of blood vessels in the body. It is also a key factor in embryonic development and cell migration.

PDGFB protein-related signaling pathways

In terms of signaling pathways, PDGFB exerts its effects primarily through its receptor, the PDGFR-beta. Once PDGFB binds to PDGFR-beta, it activates the receptor and initiates a cascade of downstream intracellular signaling pathways, including the PI3K-Akt pathway, MAPK pathway and JAK-STAT pathway. These pathways play critical roles in various processes, such as cell proliferation, survival, differentiation, migration, and apoptosis.

PDGFB protein-related diseases

The dysregulation of PDGFB signaling pathways has been associated with several diseases. Overexpression of PDGFB has been found in malignant tumors, including glioblastoma, and is associated with tumor progression and angiogenesis. Aberrant PDGFB signaling has also been implicated in other pathological conditions, such as atherosclerosis, restenosis, and fibrotic disorders. Furthermore, mutations in the PDGFB gene or its receptor led to primary familial brain calcification, a condition characterized by abnormal deposits of calcium in the brain.

Given the role of PDGFB in various pathological conditions, it has become an attractive candidate for the development of therapeutic strategies. Targeting PDGFB or its receptor through the use of monoclonal antibodies, receptor tyrosine kinase inhibitors, or antisense oligonucleotides has shown promise in preclinical and clinical studies for the treatment of a variety of diseases, including cancer and vascular diseases.

List of drug candidates related to PDGFB protein

Several drug candidates related to the PDGFB protein have been explored. Imatinib, a tyrosine-kinase inhibitor, is one of the most well-known drugs that inhibit the PDGFR-beta pathway and has been used in the treatment of chronic myeloid leukemia and gastrointestinal stromal tumors. Other inhibitors including nilotinib, sunitinib and sorafenib, which have broader specificity for multiple tyrosine kinases including PDGFR, are also being currently used in the clinical setting.