1228591-30-7 Usage
Description
TAK-632 is a selective pan-RAF inhibitor, which is a type of pharmaceutical compound designed to target and inhibit the activity of RAF proteins. RAF proteins are involved in various cellular processes, including cell growth and survival, and are often mutated in various types of cancer. TAK-632 works by inducing RAF dimerization but inhibiting its kinase activity, making it a promising candidate for cancer treatment.
Uses
Used in Anticancer Applications:
TAK-632 is used as an anticancer agent for BRAFand NRAS-mutated melanoma cells that have acquired resistance to BRAF inhibitors. It exhibits antitumor activity by inhibiting the kinase activity of RAF proteins, which are often mutated in these types of cancer cells. This inhibition can help to slow down or stop the growth and progression of the tumor.
Used in Drug Resistance Research:
TAK-632 is also used in research to study the mechanisms of drug resistance in cancer cells. By understanding how cancer cells develop resistance to BRAF inhibitors, researchers can develop new strategies to overcome this resistance and improve the effectiveness of existing treatments.
Used in Drug Development:
TAK-632 serves as a valuable tool in the development of new cancer therapies. Its selective inhibition of RAF proteins can be used as a starting point for the design of new drugs that target specific cancer-related pathways. Additionally, its ability to overcome drug resistance in certain cancer cells makes it a promising candidate for further research and development in the field of oncology.
Biological Activity
tak-632 is a selective inhibitor of braf, craf and braf-v600e kinase with ic50 value of 8.3 nm, 1.4 nm and 2.4 nm [1].raf kinases are a family of three serine/threonine-specific protein kinases and play an important role in the ras-raf-mek-erk signal transduction cascade, as well as the mitogen-activated protein kinase (mapk) cascade [2].tak-632 is a potent pan-raf kinase inhibitor and has a higher selectivity compared with the reported pan-raf kinase inhibitor vemurafenib. when tested with sk-mel-2 cells, tak-632 showed induction on the braf-craf dimmers formation in a dose-dependent manner. in melanoma cell lines a375 and sk-mel-2, tak-632 exhibited significant antiproliferative effects with gi50 value of 6 nom/l and 11 nom/l, respectively [1].in mouse model with sk-mel-2 subcutaneous xenograft, oral administration of tak-632 caused significant reduction of phosphorylated erk and tumor growth at the dose of 60 or 120 mg/kg/d once daily for 21 days without severe toxicity [1].it is also reported that tak-632 is a potent inhibitor of perk with ic50 value of 25 nm [1].
references
[1]. nakamura, a., et al., antitumor activity of the selective pan-raf inhibitor tak-632 in braf inhibitor-resistant melanoma. cancer res, 2013. 73(23): p. 7043-55.[2]. korkut, a., et al., perturbation biology nominates upstream-downstream drug combinations in raf inhibitor resistant melanoma cells. elife, 2015. 4.
Check Digit Verification of cas no
The CAS Registry Mumber 1228591-30-7 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,2,2,8,5,9 and 1 respectively; the second part has 2 digits, 3 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 1228591-30:
(9*1)+(8*2)+(7*2)+(6*8)+(5*5)+(4*9)+(3*1)+(2*3)+(1*0)=157
157 % 10 = 7
So 1228591-30-7 is a valid CAS Registry Number.
1228591-30-7Relevant articles and documents
Discovery of a selective kinase inhibitor (TAK-632) targeting pan-RAF inhibition: Design, synthesis, and biological evaluation of C -7-substituted 1,3-benzothiazole derivatives
Okaniwa, Masanori,Hirose, Masaaki,Arita, Takeo,Yabuki, Masato,Nakamura, Akito,Takagi, Terufumi,Kawamoto, Tomohiro,Uchiyama, Noriko,Sumita, Akihiko,Tsutsumi, Shunichirou,Tottori, Tsuneaki,Inui, Yoshitaka,Sang, Bi-Ching,Yano, Jason,Aertgeerts, Kathleen,Yoshida, Sei,Ishikawa, Tomoyasu
, p. 6478 - 6494 (2013/09/23)
With the aim of discovering a selective kinase inhibitor targeting pan-RAF kinase inhibition, we designed novel 1,3-benzothiazole derivatives based on our thiazolo[5,4-b]pyridine class RAF/VEGFR2 inhibitor 1 and developed a regioselective cyclization methodology for the C-7-substituted 1,3-benzothiazole scaffold utilizing meta-substituted anilines. Eventually, we selected 7-cyano derivative 8B (TAK-632) as a development candidate and confirmed its binding mode by cocrystal structure with BRAF. Accommodation of the 7-cyano group into the BRAF-selectivity pocket and the 3-(trifluoromethyl)phenyl acetamide moiety into the hydrophobic back pocket of BRAF in the DFG-out conformation contributed to enhanced RAF potency and selectivity vs VEGFR2. Reflecting its potent pan-RAF inhibition and slow off-rate profile, 8B demonstrated significant cellular activity against mutated BRAF or mutated NRAS cancer cell lines. Furthermore, in both A375 (BRAFV600E) and HMVII (NRASQ61K) xenograft models in rats, 8B demonstrated regressive antitumor efficacy by twice daily, 14-day repetitive administration without significant body weight loss.
