YF135 是一种高效的可逆共价KRASG12CPROTAC。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。
| 生物活性 | YF135 is an efficient and reversible-covalentKRASG12CPROTAC. 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 ofKRASG12Cin a reversible manner and decreases phospho-ERK level through the E3 ligase VHL mediatedproteasomepathway[1]. |
体外研究
(In Vitro) | YF135 inhibits the proliferation of H358 and H23 cells withIC50values of 153.9 and 243.9 nM, respectively[1].
YF135 obviously decreases the protein level of KRASG12Cand 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 KRASG12Cthrough the E3 ligase VHL mediated proteasome pathway. YF135 covalently bind to KRASG12Cand VHL ligase to form a ternary complex[1].
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 ofKRASG12Cand phospho-ERK in a time (3 μM, 0-36 h) and dose (0-10 μM, 24 h) dependent manner, withDC50values 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 onKRASG12Cand decreased the level of phospho-ERK, while the washout by fresh medium significantly rescued such effects. |
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| 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. |
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