Cancer Growth Blocker Dabrafenib (GSK2118436)
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Synonyms: Dabrafenib;N-[3-[5-(2-Amino-4-pyrimidinyl)-2-(tert-butyl)-4-thiazolyl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide;Dabrafenib free base(GSK2118436A);Dabrafenib (GSK2118436);GSK2118436A;Dabrafenib (GSK2118436A);Dabrafenib KB-57246;Debrafenib API
Dabrafenib is a type of biological therapy drug called a cancer growth blocker. It is also known by its brand name Tafinlar. Dabrafenib is a treatment for people with melanoma skin cancer that has spread to other parts of the body or can't be removed with surgery.
Dabrafenib (trade name Tafinlar, GSK2118436) is a drug for the treatment of cancers associated with a mutated version of the gene BRAF. Dabrafenib acts as an inhibitor of the associated enzyme B-Raf, which plays a role in the regulation of cell growth. Dabrafenib has clinical activity with a manageable safety profile in clinical trials of phase 1 and 2 in patients with BRAF(V600)-mutated metastatic melanoma.
How debrafenib works
About half of all melanoma skin cancers make too much BRAF protein due to a change in the BRAF gene. The BRAF protein makes cells grow and divide. Debrafenib stops cells producing the BRAF protein so this treatment can slow or stop the growth of the cancer.
BRAF activates MEK through its protein kinase activity, which enables it to carry out a chemical reaction that alters MEK’s structure. Normally, the protein kinase activity of BRAF is very low unless it is activated by RAS. A mutation of the DNA that carries the genetic code for BRAF results in a change in just one of its building block amino acids, the 600th in the protein chain. The most common mutation changes the normal amino acid, valine (V), into glutamic acid (E), so it is frequently designated the V600E mutation. The second most common mutation changes valine to lysine (K), so it is designated V600K. Both of these mutations make BRAF’s protein kinase activity permanently very high, so it no longer depends on signals coming from the receptor through RAS. An obvious way to stop the mutant BRAF is to design a drug that attaches to the protein and blocks its kinase activity. Dabrafenib was specifically designed to block the activity of the V600E mutant form of BRAF. It also has a similar level of blocking activity for the V600K mutant in laboratory tests.
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