PWT143, formerly known as ME-401, is an orally bioavailable inhibitor of the delta isoform of phosphatidylinositide 3-kinase (PI3K), with potential antineoplastic activity. The PI3K-delta inhibitor PWT143 selectively inhibits the delta isoform of PI3K after oral administration, preventing the activation of the PI3K/AKT signaling pathway. In tumor cells that overexpress PI3K-delta, this both reduces proliferation and causes cell death. The growth and survival of hematologic cancer cells are significantly influenced by PI3K-delta. In order to maintain PI3K signaling in healthy, non-cancerous cells, PI3K-delta is specifically targeted for inhibition. PI3K, an enzyme that is frequently overexpressed in cancer cells, is essential for the regulation and survival of tumor cells.

Physicochemical Properties

Molecular Formula	C31H40N8O3S
Molecular Weight	604.766104698181
Exact Mass	604.294
Elemental Analysis	C, 61.57; H, 6.67; N, 18.53; O, 7.94; S, 5.30
CAS #	1595129-71-7
Related CAS #	1595129-71-7;Zandelisib HCl Zandelisib mesylate;
PubChem CID	73441802
Appearance	White to off-white solid powder
LogP	4.6
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	8
Heavy Atom Count	43
Complexity	1010
Defined Atom Stereocenter Count	0
InChi Key	PGTXVGREXBMCCY-UHFFFAOYSA-N
InChi Code	InChI=1S/C31H40N8O3S/c1-31(2,21-23-9-5-6-10-24(23)22-13-15-37(3)16-14-22)36-27-33-28(38-17-19-42-20-18-38)35-29(34-27)39-26-12-8-7-11-25(26)32-30(39)43(4,40)41/h5-12,22H,13-21H2,1-4H3,(H,33,34,35,36)
Chemical Name	N-[2-methyl-1-[2-(1-methylpiperidin-4-yl)phenyl]propan-2-yl]-4-(2-methylsulfonylbenzimidazol-1-yl)-6-morpholin-4-yl-1,3,5-triazin-2-amine
Synonyms	Zandelisib; PWT-143; PWT143; PWT 143; ME-401; ME 401; ME401
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

ln Vivo	ME-401 is an oral, once-daily, selective PI3Kδ inhibitor that is being tested in clinical settings for the treatment of B-cell cancers. It has an ideal pharmacologic profile. To exert its mechanism of action, ME-401 can bind to the target with high affinity, be orally absorbed, spread to the target tissues, enter and accumulate in the target cells, and bind to the target. [2]
Animal Protocol	CD-1 mice, Sprague Dawley (SD) rats, Female BALB/c mice, Beagle dogs, Cynomolgus monkeys 10 mg/kg for mice, 5 mg/kg for rats, 2 mg/kg for dogs and monkeys Oral gavage
References	[1]. Clin Ther. 2018 Nov;40(11):1855-1867. [2]. Target Oncol. 2019 Oct;14(5):603-611.

Solubility Data

Solubility (In Vitro)

DMSO: 4.6~20 mg/mL (7.64~33.1mM) H2O: <0.1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (3.44 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 (3.44 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (3.44 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	1.6535 mL	8.2676 mL	16.5352 mL
	5 mM	0.3307 mL	1.6535 mL	3.3070 mL
	10 mM	0.1654 mL	0.8268 mL	1.6535 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.