MS170
目录号 : GC65466MS170 是一种有效的选择性 PROTAC AKT 降解剂。MS170 消耗细胞总 AKT (T-AKT),DC50 值为 32 nM。MS170 与 AKT1、AKT2 和 AKT3 结合,Kd 分别为 1.3 nM、77 nM 和 6.5 nM。
Cas No.:2376136-61-5
Sample solution is provided at 25 µL, 10mM.
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MS170 is a potent and selective PROTAC AKT degrader. MS170 depletes cellular total AKT (T-AKT) with the DC50 value of 32 nM. MS170 binds to AKT1, AKT2, and AKT3 with Kds of 1.3 nM, 77 nM, and 6.5 nM, respectively[1].
Cereblon (CRBN)-recruiting degrader MS170 is an effective AKT degrader without a ″hook effect″. MS170 selectively induces robust AKT protein degradation, inhibits downstream signaling, and suppresses cancer cell proliferation. MS170 concentration- and time-dependently induces AKT degradation through the ubiquitin-proteasome system (UPS)[1]. MS170 (10 nM-10 μM) effectively inhibits the proliferation in multiple cancer cell lines[1]. MS170 (1 nM-10 μM) concentration-dependently depletes cellular total AKT (T-AKT) with the DC50 value of 32±18 nM[1].
MS170 (a single intraperitoneal injection at a dose of 50 mg/kg) is bioavailable in mice via IP injection[1].
[1]. Yu X, et al. Design, Synthesis, and Evaluation of Potent, Selective, and Bioavailable AKT Kinase Degraders. J Med Chem. 2021;64(24):18054-18081.
Cas No. | 2376136-61-5 | SDF | Download SDF |
分子式 | C45H56ClN9O7 | 分子量 | 870.44 |
溶解度 | 储存条件 | Store at -20°C | |
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1 mg | 5 mg | 10 mg | |
1 mM | 1.1488 mL | 5.7442 mL | 11.4884 mL |
5 mM | 0.2298 mL | 1.1488 mL | 2.2977 mL |
10 mM | 0.1149 mL | 0.5744 mL | 1.1488 mL |
第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量) | ||||||||||
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1. 首先保证母液是澄清的;
2.
一定要按照顺序依次将溶剂加入,进行下一步操作之前必须保证上一步操作得到的是澄清的溶液,可采用涡旋、超声或水浴加热等物理方法助溶。
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Design, Synthesis, and Evaluation of Potent, Selective, and Bioavailable AKT Kinase Degraders
J Med Chem 2021 Dec 23;64(24):18054-18081.PMID:34855399DOI:10.1021/acs.jmedchem.1c01476.
The serine/threonine kinase AKT functions as a critical node of the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (m-TOR) signaling pathway. Aberrant activation and overexpression of AKT are strongly correlated with numerous human cancers. To date, only two AKT degraders with no structure-activity relationship (SAR) results have been reported. Through extensive SAR studies on various linkers, E3 ligase ligands, and AKT binding moieties, we identified two novel and potent AKT proteolysis targeting chimera (PROTAC) degraders: von Hippel-Lindau (VHL)-recruiting degrader 13 (MS98) and cereblon (CRBN)-recruiting degrader 25 (MS170). These two compounds selectively induced robust AKT protein degradation, inhibited downstream signaling, and suppressed cancer cell proliferation. Moreover, these two degraders exhibited good plasma exposure levels in mice through intraperitoneal injection. Overall, our comprehensive SAR studies led to the discovery of degraders 13 and 25, which are potentially useful chemical tools to investigate biological and pathogenic functions of AKT in vitro and in vivo.