| Description | IHMT-PI3Kδ-372 is a selective inhibitor of PI3Kδ with an IC50 of 14 nM and can be used in studies about chronic obstructive pulmonary disease. |
| In vitro | In Raji cells, IHMT-PI3Kδ-372 (0.03-3 μM) inhibits PI3Kδ-mediated AKT T308 phosphorylation (EC50 = 67 nM).IHMT-PI3Kδ-372 moderately inhibits CYP2C9 (IC50 = 2.7 μM) and no apparently inhibits CYP1A2, CYP2B6, CYP2C19, and CYP3A4 (IC50s > 10 μM)[1]. |
| In vivo | IHMT-PI3Kδ-372 (1-5 mg/kg; inhalation) improves lung function and reduced the inflammatory patterns characteristic of COPD with better forced expiratory volume in FEV1, FVC, and PEF. IHMT-PI3Kδ-372 dose-dependently decreases the inflammatory cell and reduces the abnormally high level of leukocytes including the alveolar macrophages, neutrophils, and lymphocytes. In rats, IHMT-PI3Kδ-372 (5 mg/kg; inhalation) displays a half-life of 2.3 h, low exposure of 66 ng/mL, and high clearance of 348.5 mL/min/kg in plasma and high exposure of 5599 ng/g (6 h after inhalation) in lung tissue[1]. |
| Target activity | CYP2C9:2.7 μM (IC50), PI3Kδ:14 nM (IC50) |
| Synonyms | IHMT-PI3Kδ-372 |
| molecular weight | 503.5 |
| Molecular formula | C26H23F2N7O2 |
| CAS | 2429889-62-1 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 37.8 mg/mL (75.1 mM), Sonication is recommended. |
| References | 1. Feng Li, et al. Discovery of (S)-2-(1-(4-Amino-3-(3-fluoro-4-methoxyphenyl)-1 H-pyrazolo[3,4- d]pyrimidin-1-yl)propyl)-3-cyclopropyl-5-fluoroquinazolin-4(3 H)-one (IHMT-PI3Kδ-372) as a Potent and Selective PI3Kδ Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease. J Med Chem. 2020 Nov 25;63(22):13973-13993. |