Bcl-2 family of proteins first discovered in B-cell lymphomain of chromosomal translocations have No. 14, 18, it is a lymphoma translocation gene protein. This typical chromosomal translocations can occur in 70-95% of follicular lymphoma. One of the most important features of cancer that does not follow the normal cell death program (apoptosis) and excessive proliferation. In the process of apoptosis, Bcl-2 family proteins play an important role. Bcl-2 family of proteins is important on the regulation of outer mitochondrial membrane (OMM) integrity, in the intrinsic pathway of apoptosis, and determines the sensitivity of cells to apoptotic response. Meanwhile, in-depth study of Bcl-2 family members, provide targets for the development of new anticancer drugs.
The past, many natural products are considered to be potential Bcl-2
Inhibitors, such as antimycin A (AMA). It is reported that in human kidney cancer treatment, AMA is able to enhance the expression of DR5, inhibited the expression of Bcl-2, and enhance tumor necrosis factor-related apoptosis-inducing ligand induced apoptosis. Celandine base is a plant alkaloid, which can disrupt the formation of Bcl-xl / Bax complex, thereby inhibiting tumor growth, through the activation of the mitochondrial pathway, celandine base regulate Bcl-2 protein family expression to induce apoptosis. Studies have shown that a dose of CHE (chelerythrine chloride, celandine base chloride) can damage the mitochondrial membrane potential, release of cytochrome C, activation of caspase-3 and poly ADP-ribose polymerase cleavage to induce apoptosis .
Bcl-2 inhibitors will undoubtedly become a hot research field of anticancer drugs, the application of computer-aided techniques to design, screening or optimized to Bcl-2 as a target for small-molecule inhibitors compared to conventional methods exhibit certain advantages. On the basis of further research on tumor cell apoptosis mechanism, breaking the resistance to future research is still anti-tumor drug development difficult.
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