Extended Data Fig. 5: CDK4/6-directed degradation is more effective than CDK4/6i in CDK4/6i-S tumor cells.
From: Distinct CDK6 complexes determine tumor cell response to CDK4/6 inhibitors and degraders
a, MCL cell lines were treated with 0.1 µM PB or MS140 at different time points. Lysates were immunoblotted with the indicated antibodies. b, Colo205 cells expressing Dox-inducible shCDK4 or shCDK6 were treated with or without 0.1 µg/ml doxycycline for 72 hr and cell lysates were subjected to immunoblotting with the indicated antibodies. c, Colo205 cells expressing Dox-inducible shCDK4 or shCDK6 were treated with or without 0.1 µg/ml doxycycline for 10 days followed by crystal violet staining. d, Dependency score of CDK4 and CDK6 from cancer cell line encyclopedia (CCLE) and Depmap portal database. e, GI50 values of PB and MS140 in hematologic cancer cell lines. f, Growth curve for an efficacy assay in JeKo-1 tumor xenografts in nude mice treated with vehicle or MS140 (25 mg/kg, b.i.d) or PB (50 mg/kg, q.d.) for 21 days. Each treatment contained 8 animals (n=8). Data represent mean ± SEM. g, Body weight in mice bearing JeKo-1 tumors treated with vehicle (n=8) or PB (50 mg/kg, q.d., n=8) or MS140 (25 mg/kg, b.i.d., n=8) in the course of the experiment (21 days). Data are presented as mean ± S.D. h, White blood cell, lymphocytes and red blood cell counts in C57BL/6 mice before treatment and post treatment with PB (50 mg/kg, q.d., n=8) or MS140 (25 mg/kg, b.i.d., n=7) for 21 days. Data are presented as mean ± S.D. Statistical significance was determined by paired two-tailed Student’s t-test.
