カボザンチニブリンゴ酸塩 化学特性,用途語,生産方法
効能
抗悪性腫瘍薬, チロシンキナーゼ阻害薬
説明
Cabozantinib S-MALATE，formerly known as XL184, trade name Cabometyx, is developed by Exelixis biopharmaceutical company in the United States. The drug is mainly targeted at MET and VEGFR2 tyrosine kinases that associated with the growth and proliferation of prostate cancer, inhibiting tumor metastasis and angiogenesis. Cabozantinib S-MALATE , the malate of Cabozantinib, is an effective VEGFR2 inhibitor, and IC50 is 0.035 nM. It also inhibits c-Met, Ret, Kit, Flt-1/3/4, Tie2 and AXL, and IC50 is 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM and 7 nM respectively.
Cabozantinib(Cometriq) was granted orphan drug status by the U.S. Food and Drug Administration (FDA) in January 2011. Cabozantinib(Cometriq) is approved by the U.S. FDA for medullary thyroid cancer. and advanced renal cell carcinoma in people who have received prior anti-angiogenic therapy. It is currently undergoing clinical trials for the treatment of prostate, bladder, ovarian, brain, melanoma, breast, non-small cell lung, pancreatic, and hepatocellular cancers.
化学的特性
Cabozantinib (S)-malate salt is a white to off-white solid that is practically insoluble in aqueous media.
使用
Cabozantinib malate is the malate of Cabozantinib, a potent VEGFR2 inhibitor with IC50 of 0.035 nM and also inhibits c-Met, Ret, Kit, Flt-1/3/4, Tie2, and AXL with IC50 of 1.3 nM, 4 nM, 4.6 nM, 12 nM/11.3 nM/6 nM, 14.3 nM and 7 nM, respectively.
定義
ChEBI: Cabozantinib malate is a malate salt that is the mono-(S)-malate salt of cabozantinib. A multi-tyrosine kinase inhibitor, used for the treatment of progressive, metastatic, medullary thyroid cancer. It has a role as a tyrosine kinase inhibitor, an antineoplastic agent and a prodrug. It contains a cabozantinib.
臨床応用
Cabozantinib (S)-malate (Cometriq®), which was discovered and developed by Exelixis, gained
approval by the U.S. FDA in November 2012. The drug’s indication is for the treatment of medullary
thyroid cancer (MTC), and is the second drug for this disease after AstraZeneca’s vandetanib
(Caprelsa®). The drug was successfully launched on January 24, 2013. Cabozantinib inhibits
multiple receptor tyrosine kinases including RET, MET, VEGFR-1, -2 and -3, KIT, TRKB, FLT-3,
AXL, and TIE-2. It is currently also undergoing clinical trials for the treatment of prostate, ovarian,
brain, melanoma, breast, non-small cell lung, pancreatic, hepatocellular and kidney cancers.
予防処置
Cometriq has a boxed warning that increases the incidence of gastrointestinal perforation and fistula
Formation and severe bleeding. If you have severe stomach pain, or if you feel that you are suffocating and vomiting while eating or drinking, call your doctor. Warnings and precautions include thrombosis events, Wound complications, hypertension, jaw osteonecrosis, palm-toe erythema paresthesia Syndrome (PPES), proteinuria and reversible posterior leukoencephalopathy syndrome (RPLS).
参考文献
[1] yakes f m, chen j, tan j, et al. cabozantinib (xl184), a novel met and vegfr2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. molecular cancer therapeutics, 2011, 10(12): 2298-2308. DOI:
10.1158/1535-7163.MCT-11-0264[2] zhang y, guessous f, kofman a, et al. xl-184, a met, vegfr-2 and ret kinase inhibitor for the treatment of thyroid cancer, glioblastoma multiforme and nsclc. idrugs, 2010, 13(2): 112. PMCID:
PMC3268517
カボザンチニブリンゴ酸塩 上流と下流の製品情報
原材料
準備製品