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Targeting CDK9 with selective inhibitors or degraders in tumor therapy: an overview of recent developments

As a catalytic subunit of the positive transcription elongation factor b (P-TEFb), cyclin-dependent kinase 9 (CDK9) has been demonstrated to contribute to carcinogenesis. This review focuses on the development of selective CDK9 inhibitors and proteolysis-targeting chimera (PROTAC) degraders. Twenty selective CDK9 inhibitors and degraders are introduced along with their structures, IC50 values, in vitro and in vivo experiments, mechanisms underlying their inhibitory effects, and combination regimens. NVP-2, MC180295, fadraciclib, KB-0742, LZT-106, and 21e have been developed mainly for treating solid tumors, and most of them work only on certain genotypes of solid tumors. Only VIP152 has been proven to benefit the patients with advanced high-grade lymphoma (HGL) and solid tumors in clinical trials. Continued efforts to explore the molecular mechanisms underlying the inhibitory effects, and to identify suitable tumor genotypes and combination treatment strategies, are crucial to demonstrate the efficacy of selective CDK9 inhibitors and degraders in tumor therapy.

 

Comments:

It seems like you've provided a review summary or abstract on the development of selective CDK9 inhibitors and PROTAC degraders for the treatment of cancer. CDK9 is a catalytic subunit of the positive transcription elongation factor b (P-TEFb) and has been implicated in carcinogenesis. The review highlights various compounds, their structures, inhibitory effects, and their potential use in combination regimens.

The following selective CDK9 inhibitors and degraders are mentioned in the review:

1. NVP-2
2. MC180295
3. Fadraciclib
4. KB-0742
5. LZT-106
6. 21e
7. VIP152

These compounds have been developed primarily for treating solid tumors, but most of them exhibit efficacy only in specific genotypes of solid tumors. Among them, VIP152 has shown potential benefits in clinical trials for patients with advanced high-grade lymphoma (HGL) and solid tumors.

The review emphasizes the importance of further investigations into the molecular mechanisms underlying the inhibitory effects of these compounds. Additionally, identifying suitable tumor genotypes and exploring combination treatment strategies are crucial steps to demonstrate the efficacy of selective CDK9 inhibitors and degraders in tumor therapy.

Please note that the specific details, such as IC50 values and in vitro/in vivo experiments, are not provided in the given information.

Related Products

Cat.No. Product Name Information
S8981 NVP-2 NVP-2, a potent, selective, non-neurotoxic and ATP-competitive cyclin dependent kinase 9 (CDK9) inhibitor with IC50 of 0.514 nM for CDK9/CycT activity and induces cell apoptosis.

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CDK Apoptosis related