PTC-209 | BMI-1 inhibitor

PTC-209 (315704-66-6) is an inhibitor of BMI-1 (IC₅₀ = 500 nM), part of the polycomb repressive complex 1 (PCR1).¹  It inhibited endogenous BMI-1 expression in human colorectal HCT116 and human fibrosarcoma HT1080 tumor cells resulting in reduced tumor volume as well as reduced cancer initiating cell (CIC) number.   PTC-209 displayed potent in vivo antitumor effects in several cancer models including breast², head and neck³, glioblastoma⁴, prostate⁵, colon⁵, and rhabdomyosarcoma⁶. It also promoted chemically-induced direct cardiac reprogramming of cardiac fibroblasts into cardiac myocytes.^7,8

References:

1. Kreso et al. (2013), Self-renewal as a therapeutic target in human colorectal cancer; Nat. Med. 20 29
2. Srinivasan et al. (2017), Downregulation of Bmi1 in breast cancer stem cells suppresses tumor growth and proliferation; Oncotarget. 8 38731
3. Wang et al. (2017), Pharmacological inhibition of Bmi1 by PTC-209 impaired tumor growth in head neck squamous cell carcinoma; Cancer Cell Int. 17 107
4. Kong et al. (2018), Targeting of BMI-1 with PTC-209 inhibits glioblastoma development; Cell Cycle 17 1199
5. Elango et al. (2019), Concurrent targeting of BMI1 and CDK4/6 abrogates tumor growth in vitro and in vivo; Sci. Rep. 9 13696
6. Shields et al. (2021), Epigenetic regulator BMI1 promotes alveolar rhabdomyosarcoma proliferation and constitutes a novel therapeutic target; Mol. Oncol. 1002/1878-0261.12914
7. Guo et al. (2019), Chemical suppression of specific C-C chemokine signaling pathways enhances cardiac reprogramming; J. Biol. Chem. 294 9134
8. Testa et al.. (2020),Bmi1 inhibitor PTC-209 promotes Chemically-induced Direct Cardiac Reprogramming of cardiac fibroblasts into cardiomyocytes; Sci. Rep. 10 7129