Molecular Weight (MW)

506.64

Formula

C27H31FN6OS

CAS No.

955977-50-1

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 50 mg/mL warming (98.7 mM)

Water:<1 mg/mL

Ethanol: <1 mg/mL

Synonym

Chemical Name

4-(6-((4-(cyclopropylmethyl)piperazin-1-yl)methyl)-2-(5-fluoro-1H-indol-4-yl)thieno[3,2-d]pyrimidin-4-yl)morpholine

In Vitro

Kinase Assay: PI-3065 is a novel, potent and selective inhibitor of PI3K (phosphatidylinositol 3-kinase) p110δ inhibitor with potential anticancer activity. It inhibits p110δ with an IC50 of 15 nM, and showed>70-fold selectivity over other PI3K family proteins such as p110α, p110β, p110γ with IC₅₀s of 910, 600,>10000 nM, respectively.

Cell Assay: Proliferation of 4T1 cells is assayed following a 4-h treatment with the indicated p110δ inhibitors, then washing and MTS staining are carried out after 48 h culture. PI-3065 shows no inhibition on the growth of 4T1 cells, which do not expressing detectable levels of p110δ

In Vivo

In mouse model, PI-3065 (75 mg/kg, p.o.) also suppresses 4T1 tumor growth and metastasis via inactivation of p110δ. In the LSL.KrasG12D/+; p53R172H/+; PdxCretg/+ (or KPC) model of pancreatic ductal adenocarcinoma, PI-3065 prolongs survival and reduces the incidence of macroscopic metastases and other disease-associated pathologies.

Animal model

Female WT BALB/c mice bearing 4T1 tumors

Formulation & Dosage

Dissolved in 0.5% methylcellulose with 0.2% Tween 80; 75 mg/kg; Oral administration

References

[1] Ali K, et al. Nature. 2014, 510(7505), 407-411.

Impact of pharmacological inactivation of p110δ on tumour growth and T cell responses. Nature. 2014, 510(7505), 407-411.

Characterisation of the p110δ-selective inhibitor PI-3065