| Size | Price | |
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| 500mg | ||
| 1g | ||
| Other Sizes |
| ln Vitro |
ATM-IN-13 (A36) effectively inhibited purified ATM kinase with an IC50 value of 0.3 nM[1]. ATM-IN-13 (A36) exhibited extremely high kinase selectivity, with its selectivity for ATR, mTOR, and PI3Kα being more than 3333 times higher than its IC50 value for ATM (0.3 nM), and its selectivity for DNA-PK being 493 times higher[1]. ATM-IN-13 (A36) inhibited the proliferation of HCT116 colorectal cancer cells irradiated with 2 Gy with an IC50 value of 1.7 nM[1]. ATM-IN-13 (A36) (20-40 nM; 6 days) effectively enhanced the cytotoxicity of irinotecan against HCT116 and SW620 colorectal cancer cells, and showed a more significant synergistic effect in SW620 cells[1]. ATM-IN-13 (A36) (10-20 nM) can enhance the ability of irinotecan to inhibit colony formation in colorectal cancer cells[1]. ATM-IN-13 (A36) (2 μM) can inhibit the ATM signaling pathway in irinotecan-activated HCT116 colorectal cancer cells and reduce the levels of γ-H2AX, phosphorylated ATM and phosphorylated p53[1]. ATM-IN-13 (A36) (0.5-2 μM) reduced the level of γ-H2AX in irinotecan-induced HCT116 colorectal cancer cells in a concentration-dependent manner, confirming its inhibitory effect on ATM-mediated DNA damage signaling[1]. ATM-IN-13 (A36) (0.008-1 μM; 48 h) alone did not alter the cell cycle distribution of HCT116 or SW620 colorectal cancer cells, but it enhanced irinotecan-induced G2/M phase arrest in a concentration-dependent manner [1]. ATM-IN-13 (A36) (0.25-0.5 μM; 48 h) alone did not induce apoptosis in HCT116 colorectal cancer cells, but it enhanced irinotecan-induced apoptosis in a concentration-dependent manner [1]. ATM-IN-13 (A36) has good metabolic stability in human liver microsomes, rat liver microsomes and rat/rat plasma, but poor stability in mouse liver microsomes. It has excellent water solubility at 25°C (pH 7), with a solubility of 1258.1 μg/mL [1]. ATM-IN-13 (A36) has a low likelihood of drug interactions and an IC50 > 30 μM for inhibition of CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 [1].
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| ln Vivo |
ATM-IN-13 (A36) (20-40 mg/kg; oral; once daily; 12 days) combined with liposomal irinotecan achieved tumor growth inhibition rates of 82.3% and 92.6% respectively in the HCT116 colorectal cancer xenograft model, with good safety [1]. ATM-IN-13 (10-20 mg/kg; oral; once daily; 16 days) combined with liposomal irinotecan achieved tumor growth inhibition rates of 80.8% and 91.1% respectively in the SW620 colorectal cancer xenograft model, with good safety [1].
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| Cell Assay |
Cell viability assay [1]
Cell Types: HCT116 and SW620 colorectal cancer cells Tested Concentrations: 20 nM, 40 nM (in combination with irinotecan) Incubation Duration: 6 days Experimental Results: In HCT116 cells, when the concentration was 20 nM and 40 nM, the IC50 of irinotecan decreased by 10.2-fold and 12.2-fold, respectively, when combined with irinotecan. In SW620 cells, when the concentration was 20 nM and 40 nM, the IC50 of irinotecan decreased by 84.3-fold and 253-fold, respectively, when combined with irinotecan. Cell cycle analysis [1] Cell Types: HCT116 and SW620 colorectal cancer cells Tested Concentrations: 1 μM (HCT116, monotherapy); 0.25 μM, 0.5 μM, 1 μM (HCT116, in combination with 1 μM irinotecan); 0.2 μM (SW620, monotherapy); 0.008 μM, 0.04 μM, 0.2 μM (SW620, in combination with 0.1 μM irinotecan) Incubation Duration: 48 hours Experimental Results: Using 1 μM alone had no effect on the cell cycle distribution of HCT116 cells. When used in combination with 1 μM irinotecan at concentrations of 0.25 μM, 0.5 μM, and 1 μM, the proportion of HCT116 cells in the G2/M phase increased to 66.09%, 68.8%, and 78.01%, respectively. Using irinotecan alone at a concentration of 0.2 μM had no effect on the cell cycle distribution of SW620 cells. When used in combination with 0.1 μM irinotecan at concentrations of 0.008 μM, 0.04 μM, and 0.2 μM, the proportion of SW620 cells in the G2/M phase increased to 57.92%, 58.56%, and 60.26%, respectively. |
| Animal Protocol |
Animal/Disease Models:Immunodeficient nude mice (implanted with HCT116 human colorectal cancer cells)[1]
Doses: 20 mg/kg (combined TGI); 40 mg/kg (single-drug TGI, combined TGI); 2 mg/kg (liposomal irinotecan) Route of Administration: Oral; daily; 12 days Experimental Results: The tumor growth inhibition rate (TGI) of single-drug treatment (40 mg/kg) was 41.7%. The TGI of 20 mg/kg + liposomal irinotecan was 82.3%, and the TGI of 40 mg/kg + liposomal irinotecan was 92.6%. The efficacy of the 40 mg/kg combination therapy group was statistically significantly improved compared with the single-drug group. No treatment-related deaths occurred in the high-drug group, and only moderate weight loss occurred. Animal/Disease Models:Immunodeficient nude mice (implanted with SW620 human colorectal cancer cells) [1] Doses: 10 mg/kg (combined TGI); 20 mg/kg (single-drug TGI, combined TGI); 2 mg/kg (liposomal irinotecan) Route of Administration: Oral; daily; 16 days Experimental Results: Single-drug treatment (20 mg/kg) achieved a tumor growth inhibition rate (TGI) of 28.4% without causing weight loss. The TGI rates were 80.8% (10 mg/kg + liposomal irinotecan) and 91.1% (20 mg/kg + liposomal irinotecan), respectively. The combination therapy group showed a statistically significant improvement in efficacy compared with liposomal irinotecan monotherapy. No treatment-related deaths occurred with any of the dosing regimens. |
| References |
| Molecular Formula |
C27H33N5O
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|---|---|
| Molecular Weight |
443.58
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| CAS # |
3104731-13-4
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| Appearance |
Typically exists as solids at room temperature
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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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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2544 mL | 11.2719 mL | 22.5438 mL | |
| 5 mM | 0.4509 mL | 2.2544 mL | 4.5088 mL | |
| 10 mM | 0.2254 mL | 1.1272 mL | 2.2544 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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