ChemicalBook CAS DataBase List 2429889-61-0

2429889-61-0

Name	IHMT-PI3Kδ-372 S-isomer
CAS	2429889-61-0
Molecular Formula	C26H23F2N7O2
Molecular Weight	503.5
MOL File	2429889-61-0.mol

Chemical Properties

Boiling point	722.4±70.0 °C(Predicted)
density	1.55±0.1 g/cm3(Predicted)
form	Solid
pka	3.19±0.30(Predicted)
color	White to off-white

Hazard Information

Uses

IHMT-PI3Kδ-372 is a potent and selective PI3Kδ inhibitor with an IC50 of 14 nM. IHMT-PI3Kδ-372 shows high selectivity over other class I PI3Ks (56～83 fold) and other protein kinases. IHMT-PI3Kδ-372 can be uesd for chronic obstructive pulmonary disease (COPD) research[1].

in vivo

IHMT-PI3Kδ-372 (Compound (S)-18; 1-5 mg/kg; inhalation; daily; for 28 days) improves lung function and reduced the inflammatory patterns characteristic of COPD. The lung function parameters such as forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF) are improved dose-dependently. The abnormally high level of leukocytes including the alveolar macrophages, neutrophils, and lymphocytes are also reduced. IHMT-PI3Kδ-372 decreases the inflammatory cell infiltration in a dose-dependent manner^[1].
In rats, inhalation of 5 mg/kg dose of IHMT-PI3Kδ-372 (compound (S)-18) 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 but high exposure of 5599 ng/g (6 h after inhalation) in lung tissue^[1].
IHMT-PI3Kδ-372 is stable in human, rat, and mouse liver microsomes, while it has moderate stability in monkey and dog liver microsomes^[1].

Animal Model:	Sprague-Dawley (SD) rats (5-week-old) induced with cigarette-smoke and LPS^[1]
Dosage:	1 mg/kg, 3 mg/kg, and 5 mg/kg
Administration:	Inhalation; daily; for 28 days
Result:	Improved lung function and reduced the inflammatory patterns characteristic of COPD.

IC 50

PI3Kδ: 14 nM (IC₅₀); CYP3; CYP2C9: 2.7 μM (IC₅₀)

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. DOI:10.1021/acs.jmedchem.0c01544

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