Anticancer agent 98

Anticancer agent 98 (compound 12k) is a microtubule/tubulin-polymerization inhibitor (Kd=16.9 μM). Anticancer agent 98 exerts antiproliferative potency against tumor cells, exhibits anti-angiogenesis effect in vitro. Anticancer agent 98 exhibits good human and mouse liver microsomes stability with both t1/2>300 min[1].

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> Microtubule/Tubulin

Signaling Pathways >> Cytoskeleton >> Microtubule/Tubulin

Anticancer agent 98 抑制黑色素瘤、乳腺癌和胰腺癌的癌症增殖，IC50 范围为 0.6-3 nM[1]。 Anticancer agent 98 (300 nM、1 μM 或 3 μM；2 小时) 剂量依赖性地增加 PC-3 细胞中的 β-微管蛋白加合物[1]。 Anticancer agent 98 (3.125、6.25、12.5、25 和 50 μM) 对微管蛋白具有高结合亲和力，SPR 光谱分析的 Kd 值为 16.9 μM[1]。 Anticancer agent 98 (10 μM、50 μM；0-60 分钟) 在 60 分钟内强烈抑制微管蛋白聚合[1]。 Anticancer agent 98 (100 nM; 4 h) 在体外对 COS-7 细胞具有抗增殖和抗血管生成作用[1]。 体外代谢稳定性[1] human microsomes mouse microsomes t1/2 (min) CLint (μL/min/mg) t1/2 (min) CLint (μL/min/mg) >300 <2.31 >300 <2.31

Anticancer agent 98 (2.5 mg/kg；静脉注射；每周两次，持续 2 周) 耐受性良好，在雄性 NSG 小鼠的 PC3/TxR 异种移植肿瘤中没有显着的体重减轻。相对于 Paclitaxel (HY-B0015；10 mg/kg，每周一次) 和对照组，Anticancer agent 98 还显着减缓了前列腺癌肿瘤的进展[1]。 NSG 小鼠中的药代动力学分析[1] Route Dose (mg/kg) Cmax (ng/mL) tmax (min) AUC (ng·min/mL) t1/2 (min) F (%) i.v. 4 1247 5.0 173,476 238 / p.o. 10 78.3 10.0 8161 358 2.02 Animal Model: PC3/TxR xenograft model in NSG mouse[1] Dosage: 2.5 mg/kg Administration: IV; twice weekly for 2 weeks Result: Inhibited the tumor growth in volume by approximately 85.6%. And inhibited angiogenesis by 44% related to control group. Overcame taxane resistance at a low, safe, but potent dose in vivo.

[1]. Pochampally S, et al. Design, Synthesis, and Biological Evaluation of Pyrimidine Dihydroquinoxalinone Derivatives as Tubulin Colchicine Site-Binding Agents That Displayed Potent Anticancer Activity Both In Vitro and In Vivo[J]. ACS Pharmacology & Translational Science, 2023.