PF-477736 (CAS: 952021-60-2) is a small molecule inhibitor of Chk1, a protein kinase involved in the DNA damage response pathway. It has shown potential as a cancer drug and is currently being evaluated in several clinical trials. PF-477736 was developed by Pfizer Inc., a pharmaceutical company based in New York, USA.
Chemical name: N-(4-((7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-5-(trifluoromethyl)pyrazolo[1,5-a]pyridin-3-yl)acetamide
Molecular formula: C16H11F3N6O
Formula weight: 362.3 g/mol
CAS No: 952021-60-2
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Health benefits of PF-477736: PF-477736 has the potential to offer several health benefits, primarily as a cancer drug. In preclinical studies, the drug has demonstrated efficacy against various types of cancer, including breast, lung, and colon cancer. PF-477736's mechanism of action involves inhibiting the Chk1 protein kinase, which is responsible for regulating the cell cycle checkpoint in response to DNA damage. By inhibiting Chk1, PF-477736 can prevent cancer cells from repairing DNA damage and proliferating.
Potential effects: PF-477736 has shown promising effects in preclinical and clinical studies. One Phase I study evaluated the drug's safety and tolerability in patients with advanced solid tumors and found that PF-477736 was generally well-tolerated at doses up to 600 mg twice daily. Another Phase II study tested the drug in combination with gemcitabine in patients with advanced pancreatic cancer and reported a median overall survival of 7.5 months. PF-477736 is also being investigated in combination with other chemotherapy agents.
Product mechanism: PF-477736 functions as a selective, ATP-competitive inhibitor of Chk1. Chk1 is a protein kinase that plays a critical role in the DNA damage response pathway, which is activated when cells are exposed to genotoxic stress. This pathway helps to maintain genomic stability by preventing the replication of damaged DNA. By inhibiting Chk1, PF-477736 can prevent cancer cells from repairing DNA damage and undergoing cell division, leading to apoptosis or cell death.
Safety: PF-477736 has been generally well-tolerated in clinical studies, with most adverse events being mild to moderate in severity. The most common side effects reported include nausea, vomiting, fatigue, and diarrhea. However, some serious adverse events have been reported, such as neutropenia, thrombocytopenia, and anemia. Patients with a history of cardiac disease should use caution when taking this drug, as it can cause QT interval prolongation.
Dosing information: PF-477736 is administered orally and is available in capsule form. The recommended dose varies depending on the indication and the patient's condition. In clinical studies, doses range from 100 mg to 600 mg twice daily. The drug should be taken with food to increase absorption and reduce gastrointestinal side effects.
Conclusion: PF-477736 is a promising cancer drug that targets the Chk1 protein kinase, an essential component of the DNA damage response pathway. Its ability to inhibit DNA repair and induce apoptosis makes it a potentially valuable agent in the treatment of various types of cancer, including breast, lung, and colon cancers. Although the drug has shown promising results in early clinical studies, further research is needed to determine its long-term efficacy and safety
