YF135

发表于由

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白，专注于信号通路和疾病研究领域。

YF135 

YF135 是一种高效的可逆共价 KRASG12C PROTAC。以 KRAS G12C inhibitor 48 (compound 6d) 作为配体，以 MRTX849 联动 VHL 配体为支架，设计合成YF135。YF135 通过 E3 连接酶 VHL 介导的蛋白酶体途径显著诱导 KRASG12C 的可逆降解，降低 ERK 磷酸化水平。

YF135

YF135 Chemical Structure

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生物活性

YF135 is an efficient and reversible-covalent KRASG12C PROTAC. YF135 is designed and synthesized by tethering KRAS G12C inhibitor 48 (compound 6d) as the ligand, and basing on the scaffold of MRTX849 linkage VHL ligand. YF135 significantly induces the degradation of KRASG12C in a reversible manner and decreases phospho-ERK level through the E3 ligase VHL mediated proteasome pathway[1].

体外研究
(In Vitro)

YF135 inhibits the proliferation of H358 and H23 cells with IC50 values of 153.9 and 243.9 nM, respectively[1].
YF135 obviously decreases the protein level of KRASG12C and phospho-ERK in H358 and H23 cells in a time (3 μM, 0-36 h) and dose (0-10 μM, 24 h) dependent manner, while the washout by fresh medium significantly rescues such effects[1].
YF135 induces degradation of KRASG12C through the E3 ligase VHL mediated proteasome pathway. YF135 covalently bind to KRASG12C and VHL ligase to form a ternary complex[1].

Shanghai Jinpan Biotech Co Ltd has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis

Cell Line: lung cancer cell lines H358, H23 and A549 [1]
Concentration: 0, 0.3, 1, 3, 10 μM
Incubation Time: 0, 12, 24, 36 h
Result: Obviously decreased the protein level of KRASG12C and phospho-ERK in a time (3 μM, 0-36 h) and dose (0-10 μM, 24 h) dependent manner, with DC50 values of 3.61, 1.68 μM in H358 cells, respectively, and 4.53, 1.44 μM in H23 cells, respectively.

Western Blot Analysis

Cell Line: lung cancer cell lines H358, H23 and A549 [1]
Concentration: 3 μM
Incubation Time: 24 h
Result: Induced the significant degradation on KRASG12C and decreased the level of phospho-ERK, while the washout by fresh medium significantly rescued such effects.

分子量

1179.86

Formula

C63H75ClN12O7S
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献

  • [1]. Yang F, Wen Y, Wang C, et al. Efficient targeted oncogenic KRASG12C degradation via first reversible-covalent PROTAC. Eur J Med Chem. 2022;230:114088.

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