IHMT-PI3Kδ-372 is a potent and specific PI3Kδ inhibitor (antagonist) with IC50 of 14 nM. IHMT-PI3Kδ-372 is more selective for PI3Kδ than other class I PI3Ks (56-83-fold) and other protein kinases. IHMT-PI3Kδ-372 may be utilized in the research of chronic obstructive pulmonary disease (COPD).

Physicochemical Properties

Molecular Formula	C26H23F2N7O2
Molecular Weight	503.503331422806
Exact Mass	503.188
CAS #	2429889-62-1
PubChem CID	146635374
Appearance	White to off-white solid powder
LogP	3.9
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	6
Heavy Atom Count	37
Complexity	891
Defined Atom Stereocenter Count	1
SMILES	FC1=CC=CC2=C1C(N(C([C@@H](CC)N1C3C(=C(N)N=CN=3)C(C3C=CC(=C(C=3)F)OC)=N1)=N2)C1CC1)=O
InChi Key	HTUBTEAYSCSTIY-GOSISDBHSA-N
InChi Code	InChI=1S/C26H23F2N7O2/c1-3-18(24-32-17-6-4-5-15(27)20(17)26(36)34(24)14-8-9-14)35-25-21(23(29)30-12-31-25)22(33-35)13-7-10-19(37-2)16(28)11-13/h4-7,10-12,14,18H,3,8-9H2,1-2H3,(H2,29,30,31)/t18-/m1/s1
Chemical Name	2-[(1R)-1-[4-amino-3-(3-fluoro-4-methoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]propyl]-3-cyclopropyl-5-fluoroquinazolin-4-one
HS Tariff Code	2934.99.9001
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)

Biological Activity

Targets	PI3Kδ 14 nM (IC50) CYP2C9 2.7 μM (IC50)
ln Vitro	IHMT-PI3Kδ-372 (Compound (S)-18; 0.03-3 μM; 1 hour; Raji cells) therapy suppresses PI3Kδ-mediated AKT T308 phosphorylation in Raji cells with an EC50 value of 67 nM[1]. With an IC50 of 2.7 μM, IHMT-PI3Kδ-372 (compound (S)-18) exhibits moderate suppression of CYP2C9, but no discernible inhibition of CYP1A2, CYP2B6, CYP2C19, and CYP3A4 (IC50s > 10 μM)[1].
ln Vivo	IHMT-PI3Kδ-372 (Compound (S)-18; 1–5 mg/kg; inhalation; daily; for 28 days) reduces COPD-specific inflammatory patterns and enhances lung function. There is a dose-dependent improvement in lung function measurements such as forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF). Reduced are the unusually high levels of leukocytes, which include neutrophils, lymphocytes, and alveolar macrophages. In a dose-dependent manner, IHMT-PI3Kδ-372 reduces the invasion of inflammatory cells[1]. IHMT-PI3Kδ-372 (compound (S)-18) has a half-life of 2.3 hours, low exposure to 66 ng/mL, and high clearance of 348.5 mL/min/kg in plasma after inhaling a dose of 5 mg/kg in rats. However, lung tissue has a high exposure of 5599 ng/g 6 hours after inhalation[1]. In liver microsomes from humans, rats, and mice, IHMT-PI3Kδ-372 exhibits stability, however in those from dogs and monkeys, it is only moderately stable[1].
Cell Assay	Western Blot Analysis[1] Cell Types: Raji cells Tested Concentrations: 0.03 μM, 0.1 μM, 0.3 μM, 1 μM, 3 μM Incubation Duration: 1 hour Experimental Results: Inhibited PI3Kδ-mediated AKT T308 phosphorylation in Raji cells with an EC50 value of 67 nM.
Animal Protocol	Animal/Disease Models: SD (Sprague-Dawley) rats (5weeks old) induced with cigarette-smoke and LPS[1] Doses: 1 mg/kg, 3 mg/kg, and 5 mg/kg Route of Administration: Inhalation; daily; for 28 days Experimental Results: Improved lung function and decreased the inflammatory patterns characteristic of COPD.
References	[1]. 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 Obst.

Solubility Data

Solubility (In Vitro)

DMSO: 41.67 mg/mL (82.76 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.13 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.13 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.9861 mL	9.9305 mL	19.8610 mL
	5 mM	0.3972 mL	1.9861 mL	3.9722 mL
	10 mM	0.1986 mL	0.9930 mL	1.9861 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.