同义名 :	-
	CAS号 :	1799633-27-4
	货号 :	A126292
	分子式 :	C39H37ClF4N6O6S
	纯度 :	98%
	分子量 :	829.26
	MDL号 :	MFCD31382374
	存储条件：	Pure form Sealed in dry, 2-8°C In solvent -20°C:3-6个月-80°C:12个月
	溶解度 :	-
	动物实验配方：

生物活性
描述	S63845 is a highly selective and potent MCL-1 with Kd value of 0.19nM with no discernible binding to the other BCL-2 members, BCL-2 or BCL-X and exhibited little toxicity in vivo[1]. The extremely low toxicity of S63845 compared with other BCL inhibitors may due to no affinity of S63845 to necessary functions of MCL-1 that go beyond the BH3 domain binding, anti-apoptotic functions that are inhibited by other BH3 mimetics[2]. S63845 kills H929 tumour cell lines by inducing BAX/BAK-dependent apoptosis and dose-dependently induced MCL1 protein levels in HCT-116 cells at concentration ranging in 1-300nM. S63845 exhibited MCL1-dependent anti-proliferative efficiency on haematological cancer-derived cell lines both in vitro and in vivo. Intravenously injection with S63845 at dose of 6.25, 12.5 and 25mg/kg could inhibited tumor growth in a dose-dependent manner in AMO1 multiple myeloma xenograft model and robustly improved the survival of C57BL/6–LY5.1 mice transplanted with Eμ-Myc lymphoma cells at dose of 25mg/kg. S63845 is effective against AML samples in vitro (IC50<1μM) and in vivo (dose at 12.5 and 25mg/kg), but does not readily kill normal human CD34+ donor haematopoietic progenitor cells[1]. S63845 (25 mg/kg intravenously once weekly for 6 weeks, on days 2, 9, 16, 23, 30, and 37) displayed synergistic activity with docetaxel in triple-negative breast cancer and with trastuzumab or lapatinib in HER2-amplified PDX models[3].
作用机制	S63845 specifically binds with high affinity to the BH3-binding groove of MCL1.[1]

实验方案
	1mg	5mg	10mg
1 mM 5 mM 10 mM	1.21mL 0.24mL 0.12mL	6.03mL 1.21mL 0.60mL	12.06mL 2.41mL 1.21mL

参考文献

[1]Kotschy A, Szlavik Z, et al. The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models. Nature. 2016 Oct 27;538(7626):477-482. [2]Letai A, et al. S63845, an MCL-1 Selective BH3 Mimetic: Another Arrow in Our Quiver. Cancer Cell. 2016 Dec 12;30(6):834-835. [3]Merino D, Whittle JR, et al. Synergistic action of the MCL-1 inhibitor S63845 with current therapies in preclinical models of triple-negative and HER2-amplified breast cancer. Sci Transl Med. 2017 Aug 2;9(401). pii: eaam7049.