MK-1775

Описание

MK-1775 is a small molecule inhibitor of the tyrosine kinase WEE1 with potential antineoplastic sensitizing activity. MK-1775 selectively targets and inhibits WEE1, a tyrosine kinase that phosphorylates cyclin-dependent kinase 1 (CDK1, CDC2) to inactivate the CDC2/cyclin B complex. Inhibition of WEE1 activity prevents the phosphorylation of CDC2 and impairs the G2 DNA damage checkpoint. This may lead to apoptosis upon treatment with DNA damaging chemotherapeutic agents. MK-1775 is a type of biological therapy. It is a cancer growth blocker. It stops signals that cancer cells use to divide and grow. MK-1775 has been used in trials studying the treatment of LYMPHOMA, Neoplasms, Ovarian Cancer, Tongue Carcinoma, and Adult Glioblastoma, among others.

Использование

MK 1775 is used in biological studies for the abrogation of G2/M checkpoint through WEE1 inhibition in combination with chemotherapy as a promising therapeutic approach for mesothelioma.

Клиническое использование

MK-1775 is a novel, potent and selective Wee1 kinase inhibitor used in clinical studies for the treatment of a variety of solid tumours (including lymphoma, multiple myeloma, oropharyngeal, cervical, vaginal and ovarian cancers). Nanomolar concentrations of MK-1775 radiosensitised p53-deficient human lung, breast and prostate cancer cells, but did not radiosensitise similar cell lines with wild-type p53. Consistent with the radiosensitising ability, MK-1775 attenuated radiation-induced G2 block in p53-deficient cells, whereas p53 wild-type cell lines did not. MK-1775 also significantly enhanced the anti-tumour efficacy of radiation in vivo in tumour growth delay studies, which also applied to p53-deficient tumours.