Anti-Cdk7 polyclonal antibody

Cyclin-dependent kinase (CDK) 7 has a unique functional repertoire by virtue of its dual role in transcription and cell cycle progression. Whereas CDK7 is ubiquitously expressed in various types of cancer, its downregulation leads to reduced cell proliferation. Importantly, it is now agreed that targeting transcription selectively limits the synthesis of mRNAs involved in tumor growth without causing an outage of transcription of housekeeping genes. Thus, CDK7 has been considered as a viable therapeutic target in cancer. Indeed, the development of CDK7 inhibitors has gained huge momentum with two molecules, CT7001 and SY-1365, currently under clinical development. Herein, we discuss the latest understanding of the role of CDK7 in cancer cells and provide an overview of the pharmacophores of CDK7 inhibitors, their efficacy in various cancer models, and their clinical development.

Intrahepatic cholangiocarcinoma (ICC) is a lethal malignancy with high mortality and lack of effective therapeutic targets. Here, we found that expression of cyclin-dependent kinase 7 (CDK7) was significantly associated with higher tumor grade and worse prognosis in 96 ICC specimens. Depletion of CDK7 significantly inhibited cell growth, induced a G2/M cell cycle arrest, and reduced the migratory and invasive potential in ICC cells. Subsequent experiments demonstrated that ICC cells were highly sensitive to the CDK7 inhibitor THZ1. A low concentration of THZ1 markedly inhibited cell growth, cell cycle, migration, and invasion in ICC cell lines. RNA-sequencing (RNA-seq) analysis revealed that THZ1 treatment decreased the levels of massive oncogene transcripts, particularly those associated with cell cycle and cell migration. Quantitative reverse transcriptase PCR (qRT-PCR) analysis confirmed that transcription of oncogenes involved in cell cycle regulation (AURKA, AURKB, CDC25B, CDK1, CCNA2, and MKI67) and the c-Met pathway (c-Met, AKT1, PTK2, CRK, PDPK1, and ARF6) was selectively repressed by THZ1. In addition, THZ1 exhibited significant anti-tumor activity in a patient-derived xenograft (PDX) model of ICC, without causing detectable side effects.