AZ31 is a potent and highly selective ATM inhibitor with an IC50 of <0.0012 μM. AZ31 is the first selective orally active and bioavailable ATM kinase inhibitor.
In vivo, pharmacokinetic investigation of AZ31 as a single agent and in combination with irinotecan revealed that plasma concentrations of AZ31 were highest 1-hour after administration followed by a stepwise decrease at 3, 6 and 16 hour in the combination sensitive CRC098.
| Cell Experiment | |
|---|---|
| Cell lines | CRC (metastatic colorectal cancer) cell lines: HCT15, HCT116, RKO, CaCo2, LS123 and LOVO |
| Preparation method | Six CRC cell lines were treated with AZ31 (dose 1.25, 2.5 or 5 μmol/L), SN38 (0.3125 -20 nM) or AZ31 + SN38 and proliferation was determined by an SRB assay. |
| Concentrations | 1.25, 2.5 or 5 μmol/L |
| Incubation time | 72 hours |
| Animal Experiment | |
|---|---|
| Animal models | CRC PDX models (Four-to-six week-old female athymic nude mice with implanted patient-derived colorectal adenocarcinoma tumor) |
| Formulation | 10% v/v DMSO + 90% v/v Captisol at 30% w/v |
| Dosages | 100 mg/kg-daily × 3 |
| Administration | oral gavage |
| Molecular Weight | 420.50 |
| Formula | C24H28N4O3 |
| CAS Number | 2088113-98-6 |
| Solubility (25°C) | DMSO: ≥ 40 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
| Related ATM/ATR Products |
|---|
| Tuvusertib
Tuvusertib is a selective and orally active ATR inhibitor that kills tumor cells by preventing the repair of damaged DNA with a Ki value below 1 μΜ. |
| ATR-IN-24
ATR-IN-24 is a ATR inhibitor. |
| ATM Inhibitor-6
ATM inhibitor-6 (A-193) is a selective ATM kinase inhibitor. |
| ATR-IN-21
ATR-IN-21 is a potent ATR inhibitor with an IC50 value of <1000 nM. |
| ATR-IN-23
ATR-IN-23 is a potent and selective ATR inhibitor with an IC50 of 1.5 nM. |
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