Description
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
Uses
Polycomb complex protein BMI-1 is a polycomb ring finger oncogene that regulates the p16 and p19 cell cycle inhibitor genes. It is necessary for efficient self-renewing cell divisions of stem cells in several tissues and can be over-expressed in tumors. PTC-209 is a BMI-1 inhibitor (IC50 = ~ 0.5 μM) that irreversibly impairs colorectal cancer-initiating cell (CIC) growth. It reduces tumor growth in CIC xenograft assays and abrogates colorectal cancer cell self-renewal in vivo, reducing their tumorigenic potential.[Cayman Chemical]
Biochem/physiol Actions
PTC-209 inhibits the expression of the oncogene BMI-1 (B lymphoma Mo-MLV insertion region 1 homolog), which encodes a polycomb group RING finger protein involved in cell cycle. PTC-209 lowers the self-renewal properties of colorectal cancer-initiating cells (CICs) The compound inhibits tumor growth, and reduces the levels of CICs present in colon cancer tumor xenografts in mice.
in vivo
PTC-209 (60 mg/kg body weight; subcutaneously; once a day for 11 days) significantly reduces tumor volume[1].
| Animal Model: | Nude mice (male, aged 8-10 weeks, HCT1116 cell-derived tumor)[1] |
| Dosage: | 60 mg/kg body weight |
| Administration: | Subcutaneously; once a day for 11 days |
| Result: | Significantly reduced tumor volume |
References
Kreso et al. (2013), Self-renewal as a therapeutic target in human colorectal cancer; Nat. Med. 20 29
Srinivasan et al. (2017), Downregulation of Bmi1 in breast cancer stem cells suppresses tumor growth and proliferation; Oncotarget. 8 38731
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
Kong et al. (2018), Targeting of BMI-1 with PTC-209 inhibits glioblastoma development; Cell Cycle 17 1199
Elango et al. (2019), Concurrent targeting of BMI1 and CDK4/6 abrogates tumor growth in vitro and in vivo; Sci. Rep. 9 13696
Shields et al. (2021), Epigenetic regulator BMI1 promotes alveolar rhabdomyosarcoma proliferation and constitutes a novel therapeutic target; Mol. Oncol. 1002/1878-0261.12914
Guo et al. (2019), Chemical suppression of specific C-C chemokine signaling pathways enhances cardiac reprogramming; J. Biol. Chem. 294 9134
Testa et al.. (2020),Bmi1 inhibitor PTC-209 promotes Chemically-induced Direct Cardiac Reprogramming of cardiac fibroblasts into cardiomyocytes; Sci. Rep. 10 7129
