CDK9
CDK9 (cyclin-dependent kinase 9) is a transcription-associated serine/threonine kinase that functions as the catalytic subunit of positive transcription elongation factor b (P-TEFb) and regulates productive RNA polymerase II (RNAPII) elongation through phosphorylation of the RNAPII C-terminal domain and elongation factors.[1][2] Mechanistically, CDK9-cyclin T complexes promote release of promoter-proximally paused RNAPII into gene bodies, thereby controlling transcriptional programs required for cellular responses to developmental and environmental signals.[1][2] Beyond transcriptional elongation, CDK9 contributes to transcription initiation, termination, and maintenance of appropriate transcriptional output, highlighting its central role in gene expression regulation.[1] Dysregulated CDK9 activity has been linked to multiple pathological conditions, particularly cancer, where aberrant transcriptional dependencies create vulnerability to pharmacological CDK9 inhibition.[1][3] In cancer models, activation of P-TEFb-dependent transcription supports oncogenic pathways including MYC, NF-κB, and stress-response signaling, and selective suppression of CDK9 can induce apoptotic programs and impair tumor cell proliferation.[4] Compared with related transcriptional cyclin-dependent kinases such as CDK12 and CDK13, which primarily regulate distinct transcriptional and RNA-processing programs through cyclin K-containing complexes, CDK9 acts as the principal P-TEFb kinase controlling promoter-proximal pause release and rapid transcriptional activation.[1][5] For experimental applications, small-molecule CDK9 inhibitors including flavopiridol have been widely used to suppress RNAPII-dependent transcription, investigate transcriptional addiction, and evaluate therapeutic vulnerabilities associated with transcriptional dysregulation.[1][6]
References:
- [1]. Egloff S. CDK9 keeps RNA polymerase II on track. Cell Mol Life Sci. 2021 Jul;78(14):5543-5567. [Content Brief]
- [2]. Anshabo AT, et al. CDK9: A Comprehensive Review of Its Biology, and Its Role as a Potential Target for Anti-Cancer Agents. Front Oncol. 2021 May 10;11:678559. [Content Brief]
- [3]. Constantin TA, et al. Transcription associated cyclin-dependent kinases as therapeutic targets for prostate cancer. Oncogene. 2022 Jun;41(24):3303-3315. [Content Brief]
- [4]. Yuan B, et al. Engineering of cytosine base editors with DNA damage minimization and editing scope diversification. Nucleic Acids Res. 2023 Nov 10;51(20):e105. [Content Brief]
- [5]. Fan Z, et al. CDK13 cooperates with CDK12 to control global RNA polymerase II processivity. Sci Adv. 2020 Apr 29;6(18):eaaz5041. [Content Brief]
- [6]. Phiel CJ, et al. Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J Biol Chem. 2001 Sep 28;276(39):36734-41. [Content Brief]
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CDK9 Related Products (203)
Related Products (203)
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Antibodies (1)
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CDK12 ligand-2
0 ImagesCat. No.: HY-150948CAS No.: 2519822-93-4
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CLZX-205
0 ImagesCat. No.: HY-161379CAS No.: 3033694-01-5
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CDK9-IN-23
0 ImagesCat. No.: HY-153426CAS No.: 2761572-96-5CDK9-IN-23 (Example 4) is a CDK9 inhibitor with an IC50 of <20 nM.
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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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PROTAC CDK4/6/9 degrader 1
0 ImagesCat. No.: HY-178452CAS No.: 3064994-97-1PROTAC CDK4/6/9 degrader 1 is a CDK4/6/9 PROTAC degrader. PROTAC CDK4/6/9 degrader 1 degrades CDK4, CDK6, and CDK9 in TNBC cells and inhibits TNBC cell proliferation. PROTAC CDK4/6/9 degrader 1 induces G1 phase arrest, promotes apoptosis, and suppresses cell migration and invasion in TNBC cells. PROTAC CDK4/6/9 degrader 1 can be used for the study of triple-negative breast cancer (TNBC). (Pink: CDK4/6/9 ligand (HY-168440), Blue: CRBN Ligand (HY-14658), Black: Linker (HY-178512), E3 ligase ligand-linker conjugate (HY-178515)).
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Cyclin K degrader 2
0 ImagesCat. No.: HY-177780Cyclin K degrader 2 is a molecular glue degrader of Cyclin K. By bridging CDK12 and DDB1, the receptor of the CRL4 E3 ligase, Cyclin K degrader 2 specifically induces the targeted degradation of Cyclin K within the CDK12-Cyclin K complex. Cyclin K degrader 2 can be used in studies related to acute myeloid leukemia.
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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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CDK6/9-IN-2
0 ImagesCat. No.: HY-175013CAS No.: 3068529-24-5CDK6/9-IN-2 is a highly active dual inhibitor of CDK6 (IC50 = 15 nM) and CDK9 (IC50 = 22 nM). CDK6/9-IN-2 is selective for CDK2, CDK8, and CDK11. CDK6/9-IN-2 inhibits the proliferation of HaCaT cells induced by IFN-γ/TNF-α and suppresses the STAT3 pathway and the expression of inflammatory factors. CDK6/9-IN-2 can alleviate psoriatic dermatitis and is useful in psoriasis research.
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LS-Q2
0 ImagesCat. No.: HY-182986LS-Q2 is a highly selective CDK4/9 inhibitor with IC50 values of 1.4 nM and 6.2 nM. LS-Q2 inhibits cancer cells proliferation, induces G2/M phase arrest, apoptosis and reduces pSer2 RNA polymerase II expression. LS-Q2 interacts synergistically with BET and Bcl-2 inhibitors to drive antitumor activity. LS-Q2 can be used for the research of cancer, such as malignant solid tumors.
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CDK9-IN-36
0 ImagesCat. No.: HY-173065CDK9-IN-36 (Compound T7) is a potent, selective and metabolically stable CDK9 inhibitor with an IC50 value of 1.2 nM. CDK9-IN-36 effectively suppresses cell proliferation, reduces colony formation, and induces apoptosis in Osimertinib (HY-15772)-resistant NSCLC cells by downregulating Mcl-1. CDK9-IN-36 also demonstrates antitumor efficacy in a tumor xenograft model.
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CDK9 ligand 5
0 ImagesCat. No.: HY-182810CAS No.: 3079792-42-7CDK9 ligand 5 (Compound 48) is a CDK9 ligand. CDK9 ligand 5 can be used as a ligand for target protein for PROTAC to develop and design degraders of PROTAC CDK9, such as PROTAC CDK9 degrader-9 (HY-168518). CDK9 ligand 5 can be used in cancer research.
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AG-012986 dihydrochloride
0 ImagesCat. No.: HY-182470CAS No.: 486414-32-8AG-012986 (dihydrochloride) is a pan-CDK inhibitor with Ki values of 44 nM (CDK1), 9.2 nM (CDK4), 94 nM (CDK2), and IC50 values of 22 nM (CDK5), 4 nM (CDK9). AG-012986 (dihydrochloride) causes apoptosis of T-cells by targeting upstream kinases in the p38 Mitogen-activated protein kinase (MAPK) pathway and impairing cellular survival. AG-012986 (dihydrochloride) induces cell cycle arrest, retinoblastoma protein hypophosphorylation, and reduces Ki-67 expression. AG-012986 (dihydrochloride) exerts antiproliferative activity in tumor cells, demonstrates antitumor efficacy in human xenograft models, and causes retinal and peripheral neurotoxicity, plus immune cell toxicity. AG-012986 (dihydrochloride) can be used for the research of colon carcinoma, non-small cell lung carcinoma, lung carcinoma, breast carcinoma, ovarian tumor, pancreatic carcinoma, osteosarcoma, lymphoma, leukemia, retinotoxicity.
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CDK9 ligand 3
0 ImagesCat. No.: HY-170979CAS No.: 3039540-24-1CDK9 ligand 3 is the ligand for CDK9 and can be used for synthesis of PROTAC degrader PROTAC CDK9 degrader-11 (HY-170978).
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CDK9 ligand-Linker Conjugate 1
0 ImagesCat. No.: HY-108375CAS No.: 2118356-95-7CDK9 ligand-Linker Conjugate 1 is a compound formed by conjugation of a selective CDK9 ligand and a PROTAC linker. CDK9 ligand-Linker Conjugate 1 can be further coupled with an E3 ubiquitin ligase ligand to synthesize CDK9 PROTAC (HY-103628). CDK9 ligand-Linker Conjugate 1 is applicable to the research of CDK9-related disease states.
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JTK-101
0 ImagesCat. No.: HY-119120CAS No.: 503048-34-8
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PHA-793887 hydrochloride
0 ImagesCat. No.: HY-11001ACAS No.: 718630-60-5PHA-793887 hydrochloride is a CDK inhibitor (with IC50 values of 8 nM for Cdk2, 60 nM for Cdk1, 62 nM for Cdk4, 138 nM for Cdk9). PHA-793887 hydrochloride inhibits purified GSK3β (IC50 79 nM). PHA-793887 hydrochloride reduces the phosphorylation level of nucleophosmin/cdc6, induces G1/G2/M phase arrest, and triggers Apoptosis by activating Caspase-3. PHA-793887 hydrochloride exhibits anticancer activity against leukemia. PHA-793887 hydrochloride can be used in research related to acute leukemia, chronic myeloid leukemia, and advanced/metastatic solid tumors.
