PTC-209 (PTC209

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

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]

PTC-209 has been used as a B lymphoma Mo-MLV insertion region 1 homolog (BMI1) inhibitor to study its effects on:

• the cell viability of canine osteosarcoma (OSA) cell lines
• lipidated microtubule-associated protein 1 light chain 3 (LC3B-II) and Sequestosome 1 (SQSTM1) protein levels in ovarian cancer (OvCa) cells
• cardiac reprogramming efficiency in mouse embryonic fibroblasts (MEF)

PTC 209 is a compound involved in thedown-reglation of NOTCH signaling and aids in suppressing acute leukemia cells.

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.

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[1] ANTONIJA KRESO. Self-renewal as a therapeutic target in human colorectal cancer[J]. Nature Medicine, 2013, 20 1: 29-36. DOI:10.1038/nm.3418
[2] MATHANGI SRINIVASAN. Downregulation of Bmi1 in breast cancer stem cells suppresses tumor growth and proliferation.[J]. Oncotarget, 2017: 38731-38742. DOI:10.18632/oncotarget.16317
[3] QIONG WANG. Pharmacological inhibition of Bmi1 by PTC-209 impaired tumor growth in head neck squamous cell carcinoma.[J]. Cancer Cell International, 2017: 107. DOI:10.1186/s12935-017-0481-z
[4] YU KONG. Targeting of BMI-1 with PTC-209 inhibits glioblastoma development.[J]. Cell Cycle, 2018, 17 10: 1199-1211. DOI:10.1080/15384101.2018.1469872
[5] R. ELANGO. Concurrent targeting of BMI1 and CDK4/6 abrogates tumor growth in vitro and in vivo[J]. Scientific Reports, 2019. DOI:10.1038/s41598-019-50140-0
[6] CARA E SHIELDS. Epigenetic regulator BMI1 promotes alveolar rhabdomyosarcoma proliferation and constitutes a novel therapeutic target.[J]. Molecular Oncology, 2021, 15 8: 2156-2171. DOI:10.1002/1878-0261.12914
[7] YIJING GUO. Chemical suppression of specific C-C chemokine signaling pathways enhances cardiac reprogramming.[J]. The Journal of Biological Chemistry, 2019, 294 23: 9134-9146. DOI:10.1074/jbc.ra118.006000
[8] GIANLUCA TESTA. Bmi1 inhibitor PTC-209 promotes Chemically-induced Direct Cardiac Reprogramming of cardiac fibroblasts into cardiomyocytes.[J]. Scientific Reports, 2020: 7129. DOI:10.1038/s41598-020-63992-8