WebJul 13, 2024 · BSJ-4-116 exhibits potent antiproliferative effects in Kelly CDK12 C1039F. It also decreases the level of CDK12 protein, regardless of the mutational status of the cell line. Moreover, it inhibits the growth of T-ALL cells (Jurkat and MOLT-4 cells) and sensitizes them to PARP inhibition. BSJ-4-116 also regulates DDR genes via poly (adenylation ... WebIntroduction The cyclin K (CCNK)/CDK12 complex is crucial for the transcription of genes that are activated after DNA damage (DDR genes). Studies show that CDK12 inhibition interferes with DNA repair by homologous recombination (HR) and thus produces a BRCA ness phenotype [ 1 ] [ 2 ] [ 3 ]. In this study, the effect of SR-4835, a selective dual ...
CDK12 - Wikipedia
WebOct 5, 2024 · For example, CDK12 inhibitor-specific depletion of CDKs leads to hypersensitivity of tumor cells to PARP inhibition through HR deficiency, and Dinaciclib can be used in combination with PARP inhibitors to result in impaired HR pathway and synergistic cell killing ability [114]. The second is to use high-throughput screening (HTS) … WebApr 4, 2024 · Abstract. Cyclin-dependent kinase 12 (CDK12) belongs to the cyclin-dependent kinase (CDK) family of serine/threonine protein kinases. The CDK12/cyclin K complex regulates the elongation step of RNA transcription by phosphorylating Ser2 on the carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II, and … dr philip saylor mass general
Gene expression regulation by CDK12: a versatile kinase in …
WebDec 20, 2024 · Mix and match: Structure-guided hybridization of dinaciclib (1), a potent pan CDK inhibitor, with SR-3029 (2), a compound with weak but selective CDK12 activity, resulted in lead compound 7, a highly potent and selective CDK12 inhibitor.The selectivity of compound 7 amongst the CDK family and across the kinome is supported by high … WebApr 21, 2024 · The role of CDK12 in homologous recombination repair may also implicate this gene in PARP inhibitor sensitivity, as has been demonstrated in ovarian cancer. 10 Here, we aimed to characterize the clinical course and responsiveness to systemic therapies of a large cohort of patients with CDK12-altered prostate cancer, with particular … WebCDK12 inhibition may therefore form a general strategy for radiosensitization in oncology. CDK12 is co-amplified with HER2 (ERBB2) in ~20% of breast tumours; overexpression correlates with high proliferative index and grade 3 tumour status based on tissue microarrays. Conversely, some 13% of breast cancers and 5% of ovarian cancers … dr philip scali belmont ma