2. シグナル伝達
  3. Cell Cycle/DNA Damage
  4. CDK
  5. CDK12 Isoform

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].

CDK12 関連製品 (43):

製品番号 製品名 製品効果 純度
  • HY-80013
    THZ1 Inhibitor 99.84%
    THZ1 is a selective and potent covalent CDK7 inhibitor with an IC50 of 3.2 nM. THZ1 also inhibits the closely related kinases CDK12 and CDK13 and downregulates MYC expression.
  • HY-103618
    THZ531 Inhibitor 99.86%
    THZ531 is a selective and covalent inhibitor of both CDK12 and CDK13 with IC50s of 158 nM and 69 nM, respectively.
  • HY-138293
    SY-5609 Inhibitor 99.93%
    SY-5609 (CDK7-IN-3) is an orally active, highly selective, noncovalent CDK7 inhibitor with a KD of 0.065 nM. SY-5609 shows poor inhibition on CDK2 (Ki=2600 nM), CDK9 (Ki=960 nM), CDK12 (Ki=870 nM). SY-5609 induces apoptosis in tumor cells and has antitumor activity.
  • HY-130250
    SR-4835 Inhibitor 99.73%
    SR-4835 is a potent, highly selective and ATP competitive dual inhibitor of CDK12/CDK13 (CDK12: IC50=99 nM, Kd=98 nM; CDK13: Kd=4.9 nM). SR-4835 acts in synergy with DNA-damaging chemotherapy and PARP inhibitors and provokes triple-negative breast cancer (TNBC) cell death.
  • HY-139039
    BSJ-4-116 Inhibitor 99.87%
    BSJ-4-116 is a PROTAC connected by ligands for Cereblon and CDK. BSJ-4-116 is a highly potent and selective CDK12 degrader (PROTAC) with an IC50 of 6 nM. BSJ-4-116 downregulates DDR genes through a premature termination of transcription, primarily through increasing poly(adenylation). BSJ-4-116 exhibits potent antiproliferative effects, alone and in combination with the poly(ADP-ribose) polymerase inhibitor Olaparib (HY-10162).
  • HY-181035
    DN1679 Degrader
    DN1679 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.
  • HY-114567
    GW780056X Inhibitor
    GW780056X is a CDK12 inhibitor. GW780056X decreases nuclear foci count in DM1 cells. GW780056X can be used for the research of myotonic dystrophy type 1.
  • HY-181645
    CDK12-IN-9 Inhibitor
    CDK12-IN-9 is a potent and selective CDK12 inhibitor with an IC50 of 2.2 nM. CDK12-IN-9 inhibits pSER2 (a downstream marker of CDK12/13 activity). CDK12-IN-9 can be used for the research of cancer.
  • HY-80013A
    THZ1 Hydrochloride Inhibitor 99.06%
    THZ1 Hydrochloride is a selective and potent covalent CDK7 inhibitor with an IC50 of 3.2 nM. THZ1 Hydrochloride also inhibits the closely related kinases CDK12 and CDK13 and downregulates MYC expression.
  • HY-168555
    YJ1206 Degrader
    YJ1206 is an orally active selective CDK12/CDK13 PROTAC degrader. YJ1206 induces DNA damage and genomic instability, activates the AKT pathway, and triggers apoptosis. YJ1206 reduces tumor cell viability, inhibits tumor growth, and attenuates tumor cell dissemination. YJ1206 is applicable to research related to prostate cancer and high-grade serous tubo-ovarian cancer.
  • HY-112626
    CDK12-IN-2 Inhibitor 99.36%
    CDK12-IN-2 is a potent, selective and nanomolar CDK12 inhibitor (IC50=52 nM) with good physicochemical properties. CDK12-IN-2 is also a strong CDK13 inhibitor due to CDK13 is the closest homologue of CDK12. CDK12-IN-2 shows excellent kinase selectivity for CDK12 over CDK2, 9, 8, and 7. CDK12-IN-2 inhibits the phosphorylation of Ser2 in the C-terminal domain of RNA polymerase II. CDK12-IN-2 can be used an excellent chemical probe for functional studies of CDK12.
  • HY-151110A
    PROTAC CDK12/13 Degrader-1 TFA Degrader 99.12%
    PROTAC CDK12/13 Degrader-1 (7f) TFA is a highly selective cell cycle protein-dependent kinase CDK12/CDK13 dual degrader with the DC50 values of 2.2 nM and 2.1 nM, respectively. PROTAC CDK12/13 Degrader-1 TFA has anti-proliferative activity and can be used in breast cancer research.
  • HY-162706
    BSJ-5-63 Degrader 99.97%
    BSJ-5-63 is a potent CDK12, CDK7, CDK9 PROTAC degrader. BSJ-5-63 BSJ-5-63 decreases the protein expression of CDK12, CDK7, CDK9, RNAPII, Cyclin K. BSJ-5-63 decreases the mRNA expression of BRCA1, BRCA2. BSJ-5-63 shows anticancer activity and has the potential for the research of prostate cancer (Pink: ligand for target protein (HY-150948); black: linker (HY-W140827); Blue: E3 ligase ligand (HY-112078)).
  • HY-163944
    LL-K12-18 Inhibitor 98.42%
    LL-K12-18 is a CDK12 kinase inhibitor and a dual-site molecular glue. LL-K12-18 inhibits human CDK12 with an IC50 value of 283.9 nM, and selectively degrades cyclin K via the ubiquitin-proteasome system by stabilizing the CDK12-DDB1 complex. LL-K12-18 downregulates DNA damage response genes, reduces the phosphorylation level of CTD Ser2 in RNA polymerase II, and modulates biomarkers such as ATM, RAD51, γ-H2AX and cleaved PARP, thereby effectively inducing apoptosis and inhibiting proliferation of breast cancer cells. LL-K12-18 exhibits high target selectivity and serves as a research tool for studies on triple-negative breast cancer.
  • HY-112261
    CDK12-IN-3 Inhibitor 99.86%
    CDK12-IN-3 is a potent and selective CDK12 inhibitor with an IC50 of 491 nM in enzymatic assay.
  • HY-145072
    BSJ-01-175 Inhibitor 99.88%
    BSJ-01-175 is a potent and selective CDK12/13 covalent inhibitor. BSJ-01-175 demonstrates exquisite selectivity, potent inhibition of RNA polymerase II phosphorylation, and downregulation of CDK12-targeted genes in cancer cells.
  • HY-139980
    CDK9-IN-13 Inhibitor 99.94%
    CDK9-IN-13 (compound 38) is potent and selective CDK9 inhibitor, with an IC50 of <3 nM. CDK9-IN-13 exhibits short half-lives in rodents.
  • HY-168162
    ZLC491 Degrader 98.51%
    ZLC491 is an orally active PROTAC degrader that selectively targets CDK12/CDK13 and exhibits certain oral bioavailability. ZLC491 induces cereblon- and proteasome-dependent selective degradation of CDK12 and CDK13. ZLC491 inhibits the transcription and expression of long genes, and mainly acts on a subset of DNA damage response genes. ZLC491 inhibits the proliferation of various triple-negative breast cancer cells. ZLC491 can be used in research related to triple-negative breast cancer.
  • HY-139329
    CDK12-IN-6 Inhibitor 99.15%
    CDK12-IN-6, a pyrazolotriazine, is a potent CDK12 inhibitor with an IC50 of 1.19 μM at high ATP (2 mM). CDK12-IN-6 has no effect on CDK2/Cyclin E (IC50>20 μM) and CDK9/Cyclin T1 (IC50>20 μM) at high ATP (2 mM) (WO2021116178A1).
  • HY-151110
    PROTAC CDK12/13 Degrader-1 Degrader 98.01%
    PROTAC CDK12/13 Degrader-1 (7f) is a highly selective cell cycle protein-dependent kinase CDK12/CDK13 dual degrader with the DC50 values of 2.2 nM and 2.1 nM, respectively. PROTAC CDK12/13 Degrader-1 has anti-proliferative activity and can be used in breast cancer research.