GNE-317 is a potent and selective PI3K inhibitor with potential anticncer activity. GNE-317 targets the PI3K pathway and can cross the Blood–Brain Barrier. GNE-317 was identified as having physicochemical properties predictive of low efflux by P-gp and BCRP. Studies in transfected MDCK cells showed that GNE-317 was not a substrate of either transporter. GNE-317 markedly inhibited the PI3K pathway in mouse brain, causing 40% to 90% suppression of the pAkt and pS6 signals up to 6-hour postdose. GNE-317 was efficacious in the U87, GS2, and GBM10 orthotopic models, achieving tumor growth inhibition of 90% and 50%, and survival benefit, respectively. GNE-317 could be effective in the treatment of GBM. (Clin Cancer Res; 18(22); 6239–48.)

MedKoo Cat#: 406637 Name: GNE-317 CAS#: 1394076-92-6 Chemical Formula: C18H20N6O3S Exact Mass: 400.13176 Molecular Weight: 400.4548 Elemental Analysis: C, 53.99; H, 5.03; N, 20.99; O, 11.99; S, 8.01

Synonym: GNE317; GNE 317; GNE-317.

IUPAC/Chemical Name: 5-(6-(3-methoxyoxetan-3-yl)-4-morpholinothieno[3,2-d]pyrimidin-2-yl)pyrimidin-2-amine

InChi Key: KBTBHOPRFNFYOA-UHFFFAOYSA-N

InChi Code: InChI=1S/C18H20N6O3S/c1-25-18(9-27-10-18)13-6-12-14(28-13)16(24-2-4-26-5-3-24)23-15(22-12)11-7-20-17(19)21-8-11/h6-8H,2-5,9-10H2,1H3,(H2,19,20,21)

SMILES Code: NC1=NC=C(C2=NC(N3CCOCC3)=C4C(C=C(C5(OC)COC5)S4)=N2)C=N1

Technical Data

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code: 293490

Additional Information

        

References

1: Salphati L, Shahidi-Latham S, Quiason C, Barck K, Nishimura M, Alicke B, Pang J, Carano RA, Olivero AG, Phillips HS. Distribution of the phosphatidylinositol 3-kinase inhibitors Pictilisib (GDC-0941) and GNE-317 in U87 and GS2 intracranial glioblastoma models-assessment by matrix-assisted laser desorption ionization imaging. Drug Metab Dispos. 2014 Jul;42(7):1110-6. doi: 10.1124/dmd.114.057513. Epub 2014 Apr 22. PubMed PMID: 24754926.

2: Salphati L, Heffron TP, Alicke B, Nishimura M, Barck K, Carano RA, Cheong J, Edgar KA, Greve J, Kharbanda S, Koeppen H, Lau S, Lee LB, Pang J, Plise EG, Pokorny JL, Reslan HB, Sarkaria JN, Wallin JJ, Zhang X, Gould SE, Olivero AG, Phillips HS. Targeting the PI3K pathway in the brain--efficacy of a PI3K inhibitor optimized to cross the blood-brain barrier. Clin Cancer Res. 2012 Nov 15;18(22):6239-48. doi: 10.1158/1078-0432.CCR-12-0720. Epub 2012 Sep 19. PubMed PMID: 22992516.