HEMTAC CDK4/6 degrader 1

HEMTAC CDK4/6 degrader 1 is a PROTAC connected by ligands for HSP90 and CDK4/6 with a Kd value of 35.7 μM. HEMTAC CDK4/6 degrader 1 induces CDK4/6 degradation in B16F10 melanoma cells. HEMTAC CDK4/6 degrader 1 arrests cell cycle at G0/G1 phase and induces apoptosis. HEMTAC CDK4/6 degrader 1 can be used in research of cancer[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> CDK

Signaling Pathways >> PROTAC >> PROTAC

CDK4

CDK6

HEMTAC CDK4/6 degrader 1 (compound 26; 0.01-1 μM; 24 h) 在处理过的 B16F10 细胞中诱导 CDK4 和 CDK6 降解，DC50 值 (产生 50% 蛋白质的药物浓度 降解) 约为 26 和 19 nM，Dmax (最大降解百分比) 分别为 88% 和 92%[1]。 HEMTAC CDK4/6 degrader 1 (0.01-100 μM; 72 h) 对多种人类癌细胞系具有抗增殖活性[1]。 HEMTAC CDK4/6 degrader 1 (250 nM; 24 or 48 h) 以剂量依赖的方式诱导 B16F10 细胞发生凋亡，并使细胞周期停滞在 G0/G1 期[1]。 Cell Viability Assay[1] Cell Line: B16F10, A375, HepG2, MDA-MB-231, and A549 cells Concentration: 0.01-100 μM Incubation Time: 72 hours Result: Inhibited cell growth in a dose-dependent manner. Apoptosis Analysis[1] Cell Line: B16F10 cells Concentration: 250 nM Incubation Time: 48 hours Result: Induced cell apoptosis in a dose-dependent manner. Cell Cycle Analysis[1] Cell Line: B16F10 cells Concentration: 250 nM Incubation Time: 48 hours Result: Increased the amount of B16F10 cells in the G0/G1 phase. Western Blot Analysis[1] Cell Line: B16F10 cells Concentration: 0.01, 0.05, 0.1, 0.5, and 1 μM Incubation Time: 24 hours Result: Induced CDK4/6 degradation in a dose-dependent manner.

HEMTAC CDK4/6 degrader 1 (compound 26; 20 and 40 mg/kg; i.p.; 每日一次, 持续 15 天) 对携带 B16F10 黑色素瘤异种移植物的 C57BL/6J 小鼠具有抗肿瘤功效[1]。 Animal Model: C57BL/6J mice bearing B16F10 melanoma xenografts[1] Dosage: 20 and 40 mg/kg Administration: intraperitoneal injection; daily, for 15 days Result: Inhibited tumor growth and resulted in fewer CDK4/6-positive cells and led to much more necrosis.

[1]. Li Z, et, al. Targeted Protein Degradation Induced by HEMTACs Based on HSP90. J Med Chem. 2023 Jan 12;66(1):733-751.