CDK2-IN-60
CDK2-IN-60 is an orally active, ATP-competitive selective CDK2 inhibitor with a Ki of 77 pM. CDK2-IN-60 has high selectivity for both CDK4 and CDK1. CDK2-IN-60 blocks G1/S cell cycle progression to suppress proliferation of CCNE1-amplified tumor cells. CDK2-IN-60 serves as a lead chemical probe for investigating CCNE1-amplified cancers and CDK4/6 inhibitor-resistant HR-positive breast cancer.
For research use only. We do not sell to patients.
- CAS No.: 2922859-30-9
- Formula: C18H26N6O3
- Molecular Weight:374.44
-
Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
-
Biological Activity
-
Chemical Information
- Protocols
- Purity & Documentation
- References
-
Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
CDK2 77 pM (Ki) |
In Vitro
CDK2-IN-60 (Compound19) (30 min) potently inhibits CDK2 kinase with a Ki value of 77 pM and exhibits 584-fold and 47-fold selectivity over CDK4 and CDK1 respectively[1].
CDK2-IN-60 (16 h) displays robust antiproliferative activity against CCNE1-amplified OVISE ovarian cancer cells with an EdU IC50 of 0.03 μM and 50-fold cellular selectivity over CCNE1-low SKOV3 cells[1].
CDK2-IN-60 (1 μM; 0-3 h) possesses excellent metabolic stability in human primary hepatocytes with undetectable hepatic clearance in vitro[1].
CDK2-IN-60 (5 μM; 60-80 min) shows moderate membrane permeability in MDCK cells and is identified as a substrate of human P-gp and BCRP efflux transporters via bidirectional permeability tests[1].
CDK2-IN-60 (5 μM; 6 h) presents moderate plasma protein binding measured by in vitro equilibrium dialysis assay[1].
CDK2-IN-60 selectively binds CDK2 Lys89, confirmed by molecular dynamics and kinase co-crystal structures[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
Parmacokinetics
| Species | Dose | Route | CL | Vss | T1/2 | AUC0-∞ | F | CLplasma | CLrenal | Bioavailability | Tmax |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 1 mg/kg | i.v. | 47 mL/min/kg | 1.1 L/kg | 0.3 h | / | / | / | / | / | / |
| Mice[1] | 5 mg/kg | p.o. | / | / | / | 2.9 μM·h | 61 % | / | / | / | / |
| Mice[1] | 50 mg/kg | p.o. | / | / | / | 28.7 μM·h | / | / | / | / | / |
| Rat[1] | 3 mg/kg | i.v. | / | / | / | / | / | 56 mL/min/kg | 9.7 mL/min/kg | / | / |
| Rat[1] | 5 mg/kg | p.o. | / | / | / | / | / | / | / | 67 % | 1.4 h |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:Female SCID.bg (C.B-17 SCID.bg) mice aged (6-8 weeks with an average weight of 24-26 g) were inoculated with OVCAR-3 X2.1 ovarian adenocarcinoma cells[1]
-
Dosage:10 mg/kg, 30 mg/kg, 60 mg/kg
-
Administration:p.o., once daily, for 21 days
-
Result:Exhibited dose-dependent tumor growth inhibition, with a maximum TGI of 79% at the highest tested dose.
Did not significantly affect mouse body weight.
Chemical Information
-
CAS No. 2922859-30-9
-
Molecular Weight 374.44
-
Formula C18H26N6O3
-
SMILES
O=C(NC(C)(C)C)O[C@H](CC1)C[C@H]1C2=CC(NC(C=C3)=NN(C)C3=O)=NN2
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
-
Flow cytometric DNA-content cell-cycle staining
Flow cytometric DNA-content cell-cycle staining measures the fluorescence intensity of DNA-bound fluorochromes in single cells or nuclei to estimate DNA content distributions, allowing assignment of populations to G0/G1, S, and G2/M phases by DNA histogram deconvolution. Propidium iodide (PI) intercalates into DNA, and PI fluorescence is proportional to cellular DNA content when staining is performed under conditions that make DNA accessible and minimize non-DNA signal. Cells with G2/M DNA content are expected to show approximately twice the fluorescence intensity of G0/G1 cells, while S-phase cells occupy intermediate fluorescence values. PI-based DNA-content analysis can also detect cells with fractional DNA content, often reported as sub-G1, when DNA fragmentation and extraction during staining reduce retained DNA signal in apoptotic cells. DAPI is an alternative DNA fluorochrome for univariate DNA-content analysis, while bivariate approaches combining DNA content with proliferation
-
BrdU Incorporation Assay
Bromodeoxyuridine (BrdU) incorporation assay is based on the principle that BrdU, a thymidine analog, is incorporated into newly synthesized DNA during the S phase of the cell cycle, thereby serving as a marker of DNA replication and cellular proliferation. Incorporated BrdU can be detected using anti-BrdU antibodies following DNA denaturation, enabling visualization or quantification of proliferating cells through immunochemical detection methods such as immunofluorescence or immunohistochemistry.
-
Protocol for Cell Cycle
Cell-cycle analysis by flow cytometry measures DNA content in single cells to estimate the fraction of cells in G0/G1, S, and G2/M phases. Propidium iodide intercalates into DNA, and after RNA removal with RNase, fluorescence intensity reflects cellular DNA content: 2N cells are assigned to G0/G1, cells between 2N and 4N to S phase, and 4N cells to G2/M. DNA-content analysis alone cannot reliably separate G0 from G1 or G2 from M. Ki-67 can distinguish quiescent G0 cells from cycling cells, EdU or BrdU incorporation marks active DNA synthesis in S phase, and phospho-histone H3 staining identifies mitotic cells within the 4N population.
-
Breast Cancer Modeling
Breast cancer is a heterogeneous cancer, and it has been distinguished into four subtypes: luminal A, luminal B, HER2-positive and basal-like. Molecular mutations, epigenetic alterations, hormone exposure and immune microenvironment are related to the progression of breast cancer.
-
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.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
CDK2-IN-60 Related Classifications
HY-184649 Related Classifications
Powered by Bioz