PTC-209

PTC-209, a low-molecular-weight compound that selectively inhibits BMI-1 with IC50 for 0.5μM in HT1080 cells, is a promising anticancer^[1,2]

In vitro, PTC-209 treats human colorectal cancer cells with doses between 0.1 and 10μM reduced BMI-1 protein levels in a dose-dependent manner with a concomitant reduction in cell growth^[1]. PTC-209 causes a concentration- and time-dependent decrease in the cellular viability of lung cancer cells (LNM35 and A549), breast cancer cells (MDA-MB-231 and T47D), and colon cancer cells (HT-29, HCT8/S11, and HCT-116)^[2]. Treatment with PTC-209 significantly decreased viable cell numbers in human multiple myeloma (MM) cell lines, induced a G1 cell cycle arrest, promoted apoptosis and demonstrated synergistic activity with pomalidomide and carfilzomib. In the MM microenvironment, PTC-209 impaired tube formation, impaired osteoclast development and decreased osteoblast formation in a dose-dependent manner (P < 0.01 at 1μM, respectively). Therapeutic targeting of BMI-1 by PTC-209 is a promising novel therapeutic intervention for MM^[3]

PTC-209 combined with palbociclib inhibit tumor cell proliferation, sphere and colony formation, migration, and in vivo tumor formation^[4]. PTC-209 administration significantly reduced tumor growth in a HNSCC xenograft model by Bmi1 inhibition and impaired cell proliferation in vivo^[5]. PTC-209 significantly attenuates the glioblastoma growth in a murine orthotopic xenograft model^[6]

References:
[1].Kreso A, van Galen P, et al. Self-renewal as a therapeutic target in human colorectal cancer. Nat Med. 2014;20(1):29-36.
[2].Sulaiman S, Arafat K, et al. PTC-209 Anti-Cancer Effects Involved the Inhibition of STAT3 Phosphorylation. Front Pharmacol. 2019;10:1199. Published 2019 Oct 21.
[3].Bolomsky A, Schlangen K, et al. Targeting of BMI-1 with PTC-209 shows potent anti-myeloma activity and impairs the tumour microenvironment. J Hematol Oncol. 2016;9:17. Published 2016 Mar 2.
[4]. Elango R, Vishnubalaji R, et al. Concurrent targeting of BMI1 and CDK4/6 abrogates tumor growth in vitro and in vivo. Sci Rep. 2019;9(1):13696. Published 2019 Sep 23.
[5].Wang Q, Li Z, et al. Pharmacological inhibition of Bmi1 by PTC-209 impaired tumor growth in head neck squamous cell carcinoma. Cancer Cell Int. 2017;17:107. Published 2017 Nov 21.
[6].Kong Y, Ai C, et al. Targeting of BMI-1 with PTC-209 inhibits glioblastoma development. Cell Cycle. 2018;17(10):1199-1211

PTC-209 是一种小分子化合物，可选择性抑制 BMI-1，在 HT1080 细胞中的 IC50 为 0.5μM，是一种很有前途的抗癌药物^[1,2]

在体外，PTC-209 以 0.1 到 10μM 之间的剂量处理人结直肠癌细胞，以剂量依赖性方式降低 BMI-1 蛋白水平，同时减少细胞生长^[1]。 PTC-209 导致肺癌细胞（LNM35 和 A549）、乳腺癌细胞（MDA-MB-231 和 T47D）和结肠癌细胞（HT-29、HCT8/ S11 和 HCT-116)^[2]。用 PTC-209 处理可显着降低人多发性骨髓瘤 (MM) 细胞系中的活细胞数量，诱导 G1 细胞周期停滞，促进细胞凋亡，并证明与泊马度胺和卡非佐米具有协同活性。在 MM 微环境中，PTC-209 以剂量依赖性方式损害管形成、损害破骨细胞发育和减少成骨细胞形成（P &lt；1μM 时分别为 0.01）。 PTC-209 对 BMI-1 的治疗靶向是一种很有前途的 MM 新型治疗干预措施^[3]

PTC-209 联合 palbociclib 可抑制肿瘤细胞增殖、球体和集落形成、迁移以及体内肿瘤形成^[4]。 PTC-209 给药通过 Bmi1 抑制和体内细胞增殖受损显着降低了 HNSCC 异种移植模型中的肿瘤生长^[5]。 PTC-209 显着减弱小鼠原位异种移植模型中的胶质母细胞瘤生长^[6]