KI-ARv-03
KI-ARv-03 is a potent and selective ATP-competitive CDK9 inhibitor with an IC₅₀ of 0.15 μM (at 45 μM ATP), exhibiting over 130-fold selectivity against other CDKs (including CDK1-7). KI-ARv-03 reduces androgen receptor (AR)-driven transcription and proliferation in prostate cancer cells. KI-ARv-03 can be used for leukemia, pancreatic cancer, alveolar rhabdomyosarcoma (ARMS) and castration-resistant prostate cancer (CRPC) research. KI-ARv-03 is a ligand for target protein for PROTAC. KI-ARv-03 can be used to synthesize PROTAC KI-CDK9d-32 (HY-173523)[1][2].
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- CAS No.: 2416873-72-6
- 화학식: C14H21N5
- 분자량:259.35
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Protocol
- 순도&문서
- References
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Help & FAQs
Biological Activity
제품 설명
IC50 & Target
[1]|
CDK9 0.15 μM (IC50) |
In Vitro
KI-ARv-03 binds in the ATP-pocket of CDK9, forming critical interactions with hinge residues Glu107, His108, and the DFG-motif's Asp109[1].
KI-ARv-03 (5 μM, 18 h) selectively suppressed AR-V7 transcripts in both VCaP-16 and 22Rv1 cells, an effect that translated to KLK3 downregulation only in VCaP-16 cells, with no impact on AR-FL[1].
KI-ARv-03 (0-10 μM, 48-72 h) exhibits dose-dependent anti-proliferative activity (GR₅₀ = 1.52 μM in MV-4-11; GR₅₀ = 3.26 μM in 22Rv1) and induces more robust apoptosis in MV-4-11 AML cells, suggesting a heightened susceptibility of hematological cancers to CDK9 inhibition[1].
KI-ARv-03 (0-40 μM, 1 h) directly engages CDK9 but not AR species, indicating it affects AR levels through impaired CDK9 enzymatic activity[1].
KI-ARv-03 (0.5-10 μM, 1-48 h) dose-dependently reduces RNA Pol II (pSer2/pSer7), and time-dependently depletes AR-FL, AR-V7 and AR (pSer81) levels in 22Rv1 cells, consistent with its role in CDK9-mediated transcriptional regulation of the AR locus[1].
KI-ARv-03 (5 μM, 6-24 h) triggers the depletion of AR protein through a proteasome-dependent pathway, as evidenced by rescue with MG132 (HY-13259), thereby linking CDK9 inhibition to AR protein stability[1].
KI-ARv-03 (0-10 μM, 72-120 h) dose-dependently inhibits the proliferation of MOLT-4, PSN-1, and RH-4 cells, with IC₅₀ values ranging from 279.2 nM to 9.99 μM[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:VCaP-16 and 22Rv1 cells
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Concentration:5 μM
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Incubation Time:18 h
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Result:Dramatically decreased transcript levels of KLK3 (PSA) and AR-V7 in VCaP-16 cells.
Decreased AR-V7 transcript, while KLK3 transcript levels showed no significant reduction in 22Rv1 cells.
Transcript levels of AR-FL remained unchanged in both cell lines.
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Cell Line:MV-4-11 and 22Rv1 cells
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Concentration:10 μM top, 3.16-fold dilution
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Incubation Time:48 h for MV-4-11, and 72 h for 22Rv1
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Result:Moderately increased apoptotic cell counts at high doses (10 and 3 μM), while no apoptotic cells were produced at submicromolar doses.
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Cell Line:MV-4-11 and 22Rv1 cells
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Concentration:10 μM top, 3.16-fold dilution
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Incubation Time:48 h for MV-4-11, and 72 h for 22Rv1
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Result:Inhibited cell proliferation in a dose-dependent manner.
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Cell Line:22Rv1 cells
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Concentration:0.5, 2.5, 5 and 10 μM
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Incubation Time:1, 2, 4, 6, 8, 24, and 48 h
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Result:Significantly reduced phosphorylation of RNA Pol II at Ser2 and Ser7, even at low doses.
Significantly reduced AR-FL, AR-V7 protein levels and AR phosphorylation at Ser81 starting at 6 h, with complete depletion achieved after 16 h.
The depletion of AR protein was rescued by co-treatment with the proteasome inhibitor MG132 (10 μM).
Chemical Information
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CAS No. 2416873-72-6
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분자량 259.35
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화학식 C14H21N5
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SMILES
CCCC1=NC2=CC=NN2C(N[C@H]3C[C@@H](CC3)N)=C1
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocol
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Research Protocol for Endocrine Diseases
Endocrine diseases often arise from disrupted hormone production, hormone signaling, or target-tissue responsiveness; for diabetes-focused endocrine disease models, insulin signaling regulates glucose uptake, hepatic glucose output, lipid metabolism, and β-cell compensation. Type 2 diabetes develops through interacting defects in insulin resistance, β-cell dysfunction, adipose inflammation, hepatic glucose overproduction, altered incretin signaling, and ectopic lipid metabolism. A major unresolved question is whether endocrine dysfunction is driven primarily by target-tissue insulin resistance, intrinsic β-cell failure, immune/inflammatory stress, or combined multi-organ failure that differs by disease stage.
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Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.
순도&문서
References
[1]. Richters A, et al. Modulating Androgen Receptor-Driven Transcription in Prostate Cancer with Selective CDK9 Inhibitors. Cell Chem Biol. 2021 Feb 18;28(2):134-147.e14 [Content Brief]
[2]. Toure MA, et al. Targeted degradation of CDK9 potently disrupts the MYC-regulated network. Cell Chem Biol. 2025 Apr 17;32(4):542-555.e10. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
KI-ARv-03 Related Classifications
HY-153718 Related Classifications
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