ATM-IN-13
ATM-IN-13 (A36) is an orally active, selective ATM kinase inhibitor with a human IC50 of 0.3 nM. ATM-IN-13 blocks the ATM-mediated DNA double-strand break repair signaling pathway, reduces the phosphorylation levels of ATM and p53, and inhibits ATM-dependent DNA damage response. ATM-IN-13 can be used in the research of colorectal cancer.
For research use only. We do not sell to patients.
- CAS No.: 3104731-13-4
- Formula: C27H33N5O
- Molecular Weight:443.58
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Storage:
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
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
ATM-IN-13 (A36) potently inhibits purified ATM kinase with an IC50 of 0.3 nM[1].
ATM-IN-13 (A36) exhibits high kinase selectivity, with >3333-fold selectivity over ATR, mTOR, and PI3Kα, and 493-fold selectivity over DNA-PK relative to its ATM IC50 of 0.3 nM[1].
ATM-IN-13 (A36) inhibits proliferation of 2 Gy-irradiated HCT116 colorectal cancer cells with an IC50 of 1.7 nM[1].
ATM-IN-13 (A36) (20-40 nM; 6 days) potently enhances the cytotoxicity of irinotecan in HCT116 and SW620 colorectal cancer cells, with greater synergistic effects in SW620 cells[1].
ATM-IN-13 (A36) (10-20 nM) enhances the ability of irinotecan to suppress colony formation in colorectal cancer cells[1].
ATM-IN-13 (A36) (2 μM) inhibits the irinotecan-activated ATM signaling pathway in HCT116 colorectal cancer cells, reducing levels of γ-H2AX, phosphorylated ATM, and phosphorylated p53[1].
ATM-IN-13 (A36) (0.5-2 μM) concentration-dependently reduces irinotecan-induced γ-H2AX levels in HCT116 colorectal cancer cells, confirming inhibition of ATM-mediated DNA damage signaling[1].
ATM-IN-13 (A36) (0.008-1 μM; 48 h) alone does not alter cell cycle distribution in HCT116 or SW620 colorectal cancer cells, but enhances irinotecan-induced G2/M phase arrest in a concentration-dependent manner[1].
ATM-IN-13 (A36) (0.25-0.5 μM; 48 h) alone does not induce apoptosis in HCT116 colorectal cancer cells, but enhances irinotecan-induced apoptosis in a concentration-dependent manner[1].
ATM-IN-13 (A36) has good metabolic stability in human and rat liver microsomes and mouse/rat plasma, poor stability in mouse liver microsomes, and excellent aqueous solubility of 1258.1 μg/mL at 25°C (pH 7)[1].
ATM-IN-13 (A36) has low potential for drug-drug interactions, with IC50 > 30 μM for inhibition of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HCT116 and SW620 colorectal cancer cells
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Concentration:20 nM, 40 nM (combination with irinotecan)
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Incubation Time:6 days
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Result:Reduced the irinotecan IC50 by 10.2-fold and 12.2-fold in HCT116 cells when used at 20 nM and 40 nM in combination with irinotecan, respectively.
Reduced the irinotecan IC50 by 84.3-fold and 253-fold in SW620 cells when used at 20 nM and 40 nM in combination with irinotecan, respectively.
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Cell Line:HCT116 and SW620 colorectal cancer cells
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Concentration:1 μM (HCT116, monotherapy); 0.25 μM, 0.5 μM, 1 μM (HCT116, combination with 1 μM irinotecan); 0.2 μM (SW620, monotherapy); 0.008 μM, 0.04 μM, 0.2 μM (SW620, combination with 0.1 μM irinotecan)
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Incubation Time:48 h
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Result:Had no effect on cell cycle distribution in HCT116 cells when used alone at 1 μM.
Increased the percentage of HCT116 cells in G2/M phase to 66.09%, 68.8%, and 78.01% when used at 0.25 μM, 0.5 μM, and 1 μM in combination with 1 μM irinotecan, respectively.
Had no effect on cell cycle distribution in SW620 cells when used alone at 0.2 μM.
Increased the percentage of SW620 cells in G2/M phase to 57.92%, 58.56%, and 60.26% when used at 0.008 μM, 0.04 μM, and 0.2 μM in combination with 0.1 μM irinotecan, respectively.
ATM-IN-13 (10-20 mg/kg; p.o.; daily; 16 days) in combination with liposomal irinotecan achieves 80.8% and 91.1% tumor growth inhibition, respectively, with a favorable safety profile in SW620 colorectal cancer xenografts[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Immunodeficient nude mice (implanted with HCT116 human colorectal cancer cells)[1]
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Dosage:20 mg/kg (combination TGI); 40 mg/kg (monotherapy TGI, combination TGI); 2 mg/kg (liposomal irinotecan)
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Administration:p.o.; daily; 12 days
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Result:Achieved a tumor growth inhibition (TGI) rate of 41.7% (monotherapy, 40 mg/kg).
Achieved TGI rates of 82.3% (20 mg/kg + liposomal irinotecan) and 92.6% (40 mg/kg + liposomal irinotecan).
Showed statistically significant enhanced efficacy in the 40 mg/kg combination group compared to single-agent groups.
Caused no treatment-related fatalities and only moderate body weight loss in the high-dose group.
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Animal Model:Immunodeficient nude mice (implanted with SW620 human colorectal cancer cells)[1]
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Dosage:10 mg/kg (combination TGI); 20 mg/kg (monotherapy TGI, combination TGI); 2 mg/kg (liposomal irinotecan)
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Administration:p.o.; daily; 16 days
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Result:Achieved a tumor growth inhibition (TGI) rate of 28.4% (monotherapy, 20 mg/kg) without causing body weight loss.
Achieved TGI rates of 80.8% (10 mg/kg + liposomal irinotecan) and 91.1% (20 mg/kg + liposomal irinotecan).
Showed statistically significant enhanced efficacy in combination groups compared to liposomal irinotecan monotherapy.
Caused no treatment-related fatalities across all dosing regimens.
Chemical Information
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CAS No. 3104731-13-4
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Molecular Weight 443.58
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Formula C27H33N5O
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SMILES
CC1=NN(C2=C1C=NC3=CC=C(C=C23)C4=CC=C(N=C4)OCCCN5CCCCC5)C(C)C
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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)
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