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 (54)
Related Products (54)
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PPA-037 TFA
0 ImagesCat. No.: HY-171787APurity: 99.42%PPA-037 TFA is an orally active, highly potent and selective inhibitor of cyclin-dependent kinase 12 (CDK12). PPA-037 TFA induces the degradation of cyclin K (Cyclin K), enhancing antiproliferative effects on tumor cells. PPA-037 TFA is promising for research of cancers.
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CDK12-IN-5
0 ImagesCDK12-IN-5, a pyrazolotriazine, is a potent CDK12 inhibitor with an IC50 of 23.9 nM at high ATP (2 mM). CDK12-IN-5 has no effect on CDK2/Cyclin E (IC50=173 μM) and CDK9/Cyclin T1 (IC50=127 μM) at high ATP (2 mM) (WO2021116178A1).
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PP-C8
0 ImagesPP-C8 is a potent and selective PROTAC CDK12-Cyclin K degrader. PP-C8 induces CDK12-Cyclin K degradation with DC50s of 416 and 412 nM for CDK12 and Cyclin K, respectively. PP-C8 demonstrates profound synergistic antiproliferative effects with PARP inhibitor in triple-negative breast cancer (TNBC).
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YJ9069
0 ImagesCat. No.: HY-168556YJ9069 is a CDK12/CDK13 PROTAC degrader. YJ9069 induces proteasome-dependent degradation of CDK12 and CDK13, and inhibits serine 2 phosphorylation of RNA polymerase II (RNA polymerase II). YJ9069 triggers gene length-dependent transcription elongation defects, reduces the expression of DNA damage response genes, and induces DNA damage, cell cycle arrest and apoptosis. YJ9069 inhibits tumor growth in prostate cancer models. YJ9069 can be used for the research of prostate cancer, Ewing sarcoma and breast cancer.
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HQY1428
0 ImagesHQY1428 is an orally active CDK12 inhibitor. HQY1428 inhibits DNA replication, causes G2/M arrest in SKOV3 cells, induces DNA double-strand breaks and apoptosis. HQY1428 has anti-tumor activity in the SKOV3 xenograft mouse model. HQY1428 combined with the HER2 inhibitor Lapatinib (HY-50898) in the NCI-N87 xenograft mouse model produces a synergistic therapeutic effect.
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CDK12/13-IN-3
0 ImagesCDK12/13-IN-3 (Compound 12b) is the orally active inhibitor for CDK that inhibits CDK12 and CDK13 with IC50 of 107.4 nM and 79.4 nM. CDK12/13-IN-3 inhibits the phosphorylation of Ser2 on the CTD of RNA polymerase II, induces DNA damage, and downregulates the gene expression of DNA damage response (DDR). CDK12/13-IN-3 exhibits antiproliferative activity against multiple cancer cells with IC50 of nanomolar levels. CDK12/13-IN-3 exhibits antitumor effect in mouse models, exhibits good pharmacokinetic properties with an oral bioavailability of 53.6%.
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PPA-037
0 ImagesCat. No.: HY-171787CAS No.: 2883700-83-0PPA-037 is an orally active, highly potent and selective inhibitor of cyclin-dependent kinase 12 (CDK12). PPA-037 induces the degradation of cyclin K (Cyclin K), enhancing antiproliferative effects on tumor cells. PPA-037 is promising for research of cancers.
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CDK6/PIM1-IN-1
0 ImagesCat. No.: HY-142696CAS No.: 2677026-14-9CDK6/PIM1-IN-1 is a potent and balanced dual CDK6/PIM1 inhibitor with IC50 values of 39 and 88 nM, respectively. CDK6/PIM1-IN-1 inhibits CDK4 (IC50=3.6 nM). CDK6/PIM1-IN-1 significantly inhibits acute myeloid leukemia (AML) cell proliferation, arrest cell cycle at the G1 phase, and promote cell apoptosis. CDK6/PIM1-IN-1 exhibits potent anti-AML activity.
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CDK12-IN-8
0 ImagesCDK12-IN-8 (Compound Cpd143) is an orally active and highly selective inhibitor of cyclin-dependent kinase 12 (CDK12). CDK12-IN-8 inhibits CDK12-mediated phosphorylation of the C-terminal domain (CTD) serine 2 of RNA polymerase II, interfering with gene transcription elongation and DNA damage repair pathways. CDK12-IN-8 is promising for research of cancers with high CDK12 expression such as small cell lung cancer and triple-negative breast cancer.
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DN1679
0 ImagesCat. No.: HY-181035DN1679 is a potent, selective and orally active CRBN-dependent CDK12/13 PROTAC dual degrader. DN1679 shows DC50 of 8.8/9.8 nM (MDA-MB-231), 5.1/6.4 nM (MDA-MB-157) and 17.2/15.8 nM (MDA-MB-468) for CDK12/13. DN1679 can downregulate DNA damage response gene mRNA levels, such as ATM, ATR, BRCA1 and RAD51. DN1679 demonstrates a potent synergistic anti-tumor effect companied with Olaparib (HY-10162). DN1679 can be used for research of triple-negative breast cance.
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CDK12/13-IN-2
0 ImagesCat. No.: HY-173042CAS No.: 3076450-41-1CDK12/13-IN-2 (Compound 24) is a covalent inhibitor of CDK12/13, with IC50 values of 15.5 nM and 12.2 nM for CDK12 and CDK13, respectively. CDK12/13-IN-2 can inhibit the proliferation of breast cancer cells and can be used in the research of triple-negative breast cancer.
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CDK7-IN-20
0 ImagesCat. No.: HY-151878CAS No.: 3034210-97-1
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SY-5102
0 ImagesCat. No.: HY-180355CAS No.: 2365230-48-2SY-5102 is a potent, selective, and orally active cyclin-dependent kinase (CDK7) inhibitor with a Kd value of 0.03 nM. SY-5102 occupies the ATP-binding pocket of CDK7 via non-covalent binding to inhibit CDK7 activity, and downregulates its phosphorylation of cyclin CDK and RNA polymerase II. SY-5102 inhibits cancer cell proliferation, and induces tumor growth inhibition and regression. SY-5102 can be used in research related to triple-negative breast cancer.
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GW780056X
0 ImagesCat. No.: HY-114567CAS No.: 1093294-48-4GW780056X is a CDK12 inhibitor. GW780056X decreases nuclear foci count in DM1 cells. GW780056X can be used for the research of myotonic dystrophy type 1.
