PKMYT1-IN-13
PKMYT1-IN-13 is a potent, orally active and selective PKMYT1 inhibitor that inhibits PKMYT1 with IC50 values < 10.0 nM in ADP-Glo assay and 19.9 nM in NanoBRET cellular assay. PKMYT1-IN-13 exhibits high selectivity over WEE1. PKMYT1-IN-13 shows selective antiproliferative activity in CCNE1-amplified cells, while showing minimal wild-type effects. PKMYT1-IN-13 shows antitumor efficacy in HCC1569 mouse xenografts. PKMYT1-IN-13 can be used for the research of CCNE1-amplified cancers, such as gastric, ovarian, and breast cancer.
For research use only. We do not sell to patients.
- Formula: C24H20N6O2
- Molecular Weight:424.45
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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]
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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CDK1 8.7 nM (IC50) |
PKMYT1 19.9 nM (IC50) |
PKMYT1-IN-13 (compound 20) (7 days) displays potent antiproliferative activity in CCNE1-amplified cell lines (HCC1569, MKN1, OVCAR-3, AsPc-1, SW837, SW1463, and DLD-1 FBXW7-/-) with IC50 values of 29.4, 32.8, 43.5, 83.5, 45.9, 87.8, and 328.5 nM, repectively, while showing minimal effects on their wild-type counterparts (SK-OV-3 cells (IC50= 13672 nM) and DLD-1 parent cells (IC50 > 25000 nM))[1].
PKMYT1-IN-13 (2 h) inhibits the phosphorylation of CDK1 at Thr14 in HCC1569 cells, with an IC50 of 8.7 nM[1].
PKMYT1-IN-13 exhibits favorable safety profiles (low CYP inhibition, time-dependent inhibition (TDI), hERG activity) and high kinase selectivity, achieving a selectivity score of S (10) = 0.03 across a panel of 217 kinases[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | CL | Vdss | T1/2 | AUC0-t | Tmax | Cmax | F | AUClast | AUCinf |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 2 nM | i.v. | 2.76 mL/min/kg | 0.75 L/kg | 8.05 h | 11528 ng·h/mL | / | / | / | / | / |
| Mice[1] | 10 nM | p.o. | / | / | / | 25763 ng·h/mL | 0.42 h | 16580 ng/mL | 43.0 % | / | / |
| Rat[1] | 1 nM | i.v. | 7.24 mL/min/kg | 0.53 L/kg | 2.06 h | 2278 ng·h/mL | / | / | / | / | / |
| Rat[1] | 10 nM | p.o. | / | / | / | 6826 ng·h/mL | 0.25 h | 3924 ng/mL | 30 % | / | / |
| Dog[1] | 1 nM | i.v. | 8.09 mL/min/kg | 2.00 L/kg | 4.30 h | 2053 ng·h/mL | / | / | / | / | / |
| Dog[1] | 4 nM | p.o. | / | / | / | 3416 ng·h/mL | 0.67 h | 709 ng/mL | 47.6 % | / | / |
| Rat[1] | 100 nM | p.o. | / | / | / | / | 0.25 h | 3899 ng/mL | / | 25765 ng·h/mL | 26901 ng·h/mL |
| Rat[1] | 30 nM | p.o. | / | / | / | / | / | 1104 ng/mL | 14 % | 9780 ng·h/mL | 9858 ng·h/mL |
| Rat[1] | 200 nM | p.o. | / | / | / | / | / | 2721 ng/mL | 5 % | 24783 ng·h/mL | 27136 ng·h/mL |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female NOD-SCID (6-8 weeks old) subcutaneoously implanted with HCC1569 cells[1]
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Dosage:10; 20 mg/kg
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Administration:p.o.; twice daily for 26 days
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Result:Induced dose-dependent tumor growth inhibition (TGI) with 66% TGI at 10 mg/kg and 86% TGI at 20 mg/kg.
Showed sustained inhibition of pCDK1(T14) over 24 hours postdose.
Maintained unbound plasma concentrations above the pCDK1(T14) IC90 threshold for most of the dosing interval.
Was tolerated at both dose levels, with a mean body weight loss of 8%.
Chemical Information
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Molecular Weight 424.45
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Formula C24H20N6O2
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SMILES
N#CC1=C(CNC2=O)C(C3=C4C2=C(N)[N@@]([C@@]5=C(C)C=CC(O)=C5C)C4=NC(C)=N3)=CC=C1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PKMYT1-IN-13 Related Classifications
HY-181004 Related Classifications
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