WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 205923
Description: BAY1082439 is an orally bioavailable inhibitor of the class I phosphoinositide 3-kinase (PI3K) alpha and beta isoforms with potential antineoplastic activity. PI3K alpha/beta inhibitor BAY1082439 selectively inhibits both PI3K alpha, including mutated forms of PIK3CA, and PI3K beta in the PI3K/Akt/mTOR pathway, which may result in tumor cell apoptosis and growth inhibition in PI3K-expressing and/or PTEN-driven tumor cells. By specifically targeting class I PI3K alpha and beta, this agent may be more efficacious and less toxic than pan PI3K inhibitors.
MedKoo Cat#: 205923
Chemical Formula: C25H30N6O5
Exact Mass: 494.2278
Molecular Weight: 494.552
Elemental Analysis: C, 60.72; H, 6.11; N, 16.99; O, 16.18
Synonym: BAY10-82439; BAY 10-82439; BAY-10-82439; BAY1082439; BAY 1082439; BAY-1082439.
IUPAC/Chemical Name: (S)-N-(8-(2-hydroxy-3-morpholinopropoxy)-7-methoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)-2-methylnicotinamide
InChi Key: JGNRMIWLBBNSMU-KRWDZBQOSA-N
InChi Code: InChI=1S/C25H30N6O5/c1-16-18(4-3-7-26-16)24(33)29-25-28-21-19(23-27-8-9-31(23)25)5-6-20(22(21)34-2)36-15-17(32)14-30-10-12-35-13-11-30/h3-7,17,32H,8-15H2,1-2H3,(H,28,29,33)/t17-/m0/s1
SMILES Code: C1=CC(OC[C@@H](O)CN2CCOCC2)=C(OC)C2N=C(NC(=O)C3=CC=CN=C3C)N3CCN=C3C1=2
BAY1082439 is a highly selective PI3Kα/α-balanced inhibitor. BAY 1082439 represents a new type of PI3K inhibitor with unique pharmacological and pharmacodynamic properties. BAY 1082439 has an IC50 ratio of 1:3 in biochemical assays of PI3Kα (4.9 nM) vs. PI3Kα (15.0 nM), and >1000-fold selectivity against mTOR kinase. In vivo, BAY 1082439 showed clear advantages over the strong PI3Kα inhibitor BAY 80-6946 in PTEN/PI3Kα-driven tumor models (e.g., PC3 and HEC-1B), when the two compounds were compared at their MTDs. Furthermore, BAY 1082439 has unique pharmacokinetic (PK) properties with very high plasma free fractions across all species tested (33-50%), large Vss, high clearance and intermediate T1/2. BAY 1082439 showed strong p-AKT inhibition at 2 and 5 hours post-treatment while p-AKT returned to levels comparable to the vehicle group at 24 hours in all 4 tumor models tested. Interestingly, with once daily dosing, BAY 1082439 could induce tumor regression in KPL4 (PIK3CAmut and HER2+), and tumor stasis in HEC-1B (PTENdel) and in HEC-1A (PIK3CAmut) tumor models. (source: Cancer Research: April 15, 2012; Volume 72, Issue 8, Supplement 1 doi: 10.1158/1538-7445.AM2012-2799. Proceedings: AACR 103rd Annual Meeting 2012-- Mar 31-Apr 4, 2012; Chicago, IL )