CDK12
CDK12 is a transcription-associated cyclin-dependent kinase that forms a complex with cyclin K and phosphorylates the C-terminal domain of RNA polymerase II to support transcription elongation and RNA processing[1][1]. CDK12 preferentially maintains the expression of long genes enriched in the DNA damage response (DDR), including BRCA1, ATR, FANCI, and FANCD2, thereby preserving genomic stability under replication and genotoxic stress[1][2][3]. Mechanistically, CDK12 regulates transcription elongation, co-transcriptional splicing, transcription termination, and RNA turnover, and its inhibition induces premature cleavage and polyadenylation of DDR transcripts, leading to selective suppression of DNA repair pathways[2][4][5]. In cancer models, CDK12 deficiency or inhibition impairs homologous recombination-associated repair programs, increases DNA damage signaling, and enhances sensitivity to DNA-damaging agents and PARP inhibitors[2][5][6]. Compared with the closely related kinase CDK13, which shares cyclin K as a regulatory partner and participates broadly in transcriptional regulation, CDK12 shows a more prominent role in sustaining DDR gene expression and genome maintenance[1][1]. For experimental applications, dual CDK12/CDK13 inhibitors such as THZ531 and SR-4835 have been widely used to investigate transcriptional dependencies, DDR regulation, and therapeutic vulnerabilities in cancer cells[1][7].
References:
- [1]. Rabezanahary H, et al. Live virus neutralizing antibodies against pre and post Omicron strains in food and retail workers in Québec, Canada. Heliyon. 2024 May 21;10(10):e31026. [Content Brief]
- [2]. Krajewska M, et al. CDK12 loss in cancer cells affects DNA damage response genes through premature cleavage and polyadenylation. Nat Commun. 2019 Apr 15;10(1):1757. [Content Brief]
- [3]. Kohoutek J, et al. Cyclin K goes with Cdk12 and Cdk13. Cell Div. 2012 Apr 18;7:12. [Content Brief]
- [4]. Florio E, et al. D2R signaling in striatal spiny neurons modulates L-DOPA induced dyskinesia. iScience. 2022 Oct 4;25(10):105263. [Content Brief]
- [5]. Tateishi-Karimata H, et al. Newly characterized interaction stabilizes DNA structure: oligoethylene glycols stabilize G-quadruplexes CH-π interactions. Nucleic Acids Res. 2017 Jul 7;45(12):7021-7030. [Content Brief]
- [6]. Liang S, et al. CDK12: A Potent Target and Biomarker for Human Cancer Therapy. Cells. 2020 Jun 18;9(6):1483. [Content Brief]
- [7]. Dudkiewicz-Garbicz J, et al. CDK12 and CDK13 in oncology: from RNA regulation to therapeutic targeting. Cell Oncol (Dordr). 2026 Jan 5;49(1):13. [Content Brief]
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CDK12 Related Products (53)
Related Products (53)
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CDK12-IN-9
0 ImagesCat. No.: HY-181645CAS No.: 3024723-74-5
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SR-5037
0 ImagesSR-5037 is an orally active CDK12 (IC50 = 31 nM)/CDK13 inhibitor and CycK (DC50 = 30 nM; Dmax > 98%) molecular glue degrader. SR-5037 inhibits the enzymatic activity of CDK12/CycK and CDK13/CycK complexes. SR-5037 promotes the recruitment of DDB1 to the CDK12/CycK complex, thereby triggering proteasome-mediated CycK degradation. SR-5037 degrades active CycK in mouse models of triple-negative breast cancer. SR-5037 can be used in the research of cancers such as triple-negative breast cancer.
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CDK12 ligand-2
0 ImagesCat. No.: HY-150948CAS No.: 2519822-93-4
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CDK-IN-9
0 ImagesCat. No.: HY-150641CAS No.: 3031561-92-6CDK-IN-9 (compound 24) is a potent CDK inhibitor, also as a molecular glue inducing an interaction between CDK12 and DDB1, with an IC50 values of 4 nM for CDK2/E. CDK-IN-9 leads to polyubiquitination of cyclin K and its subsequent degradation. CDK-IN-9 induce apoptosis through dephosphorylation of retinoblastoma protein and RNA polymerase II.
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CDK2-IN-42
0 ImagesCat. No.: HY-173147CDK2-IN-42 (Compound H63) is a CDK12 inhibitor with an IC50 value of 10 nM. CDK2-IN-42 has anti-ESCC (Esophageal Squamous Cell Carcinoma) cell activity. It can block transcriptional elongation, downregulate the core genes in the G1 phase to induce cell cycle arrest, and alter the CDK12-ATM/ATR-CHEK1/CHEK2 signaling axis, resulting in DNA damage. CDK2-IN-42 can effectively inhibit tumor growth in a xenograft mouse model of human ESCC KYSE150. CDK2-IN-42 holds great promise for research in the field of cancer.
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HS-36
0 ImagesCat. No.: HY-180912HS-36 is a highly selective and orally active dual inhibitor of CDK4 and CDK9 with IC50 values of 18.9 and 4.2 nM respectively. HS-36 exhibits nanomolar-level potent activity against various cancer cells, inducing G0/G1 phase arrest and promoting cell apoptosis. HS-36 efficiently inhibits tumor growth in a mouse model of MV-4-11 tumors. HS-36 can be used for the study of acute myeloid leukemia.
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YJZ5118
0 ImagesCat. No.: HY-173273CAS No.: 3031861-18-1YJZ5118 is a selective CDK12/CDK13 inhibitor with IC50 values of 39.5 nM and 26.4 nM. YJZ5118 suppresses transcription of DNA damage response genes and induces DNA damage in tumor cells. YJZ5118 inhibits proliferation and triggers apoptosis. YJZ5118 inhibits RNA polymerase II Ser2 phosphorylation and increases Akt pathway activity. YJZ5118 exhibits synergistic effects with Akt inhibitors. YJZ5118 can be used for the research of cancer, such as prostate cancer.
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Hsp90-IN-42
0 ImagesCat. No.: HY-176279Hsp90-IN-42 is a heat shock protein 90 (Hsp90) inhibitor with an IC50 of 15.65 nM against human targets. Hsp90-IN-42 destabilizes EGFR and inhibits the activation of the EGFR-Akt signaling pathway. Hsp90-IN-42 suppresses the proliferation and migration of cancer cells, induces cell cycle arrest by downregulating CDK12 and CDK13, and triggers mild apoptosis via downregulating Bcl-2 and upregulating Bax. Hsp90-IN-42 inhibits tumor growth in xenograft mouse models. Hsp90-IN-42 can be used in research related to colorectal cancer.
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YJ1206 TFA
0 ImagesCat. No.: HY-168555AYJ1206 TFA is an orally active selective CDK12/CDK13 PROTAC degrader. YJ1206 TFA induces DNA damage and genomic instability, activates the AKT pathway, and triggers apoptosis. YJ1206 TFA reduces tumor cell viability, inhibits tumor growth, and attenuates tumor cell dissemination. YJ1206 TFA is applicable to research related to prostate cancer and high-grade serous tubo-ovarian cancer.
