WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406260
Description: AZD8186 is and inhibitor of the beta isoform of phosphoinositide-3 kinase (PI3K), with potential antineoplastic activity. Upon administration, PI3Kbeta inhibitor AZD8186 selectively inhibits the activity of PI3Kbeta in the PI3K/Akt/mTOR signaling pathway, which may result in a decrease of tumor cell proliferation. It also induces cell death in PI3K-expressing cancer cells. By specifically targeting class I PI3K beta, this agent may be more efficacious and less toxic than pan PI3K inhibitors. PI3K-mediated signaling is often dysregulated in cancer cells and contributes to increased tumor cell growth, survival, and tumor resistance to a variety of antineoplastic agents. AZD8186 is currently under Phase I clinical trials.
MedKoo Cat#: 406260
Chemical Formula: C24H25F2N3O4
Exact Mass: 457.18131
Molecular Weight: 457.4
Elemental Analysis: C, 63.01; H, 5.51; F, 8.31; N, 9.19; O, 13.99
Synonym: AZD8186; AZD 8186; AZD-8186.
IUPAC/Chemical Name: (R)-8-(1-((3,5-difluorophenyl)amino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide
InChi Key: LMJFJIDLEAWOQJ-CQSZACIVSA-N
InChi Code: InChI=1S/C24H25F2N3O4/c1-14(27-18-11-16(25)10-17(26)12-18)19-8-15(24(31)28(2)3)9-20-21(30)13-22(33-23(19)20)29-4-6-32-7-5-29/h8-14,27H,4-7H2,1-3H3/t14-/m1/s1
SMILES Code: O=C(N(C)C)C1=CC([C@@H](C)NC2=CC(F)=CC(F)=C2)=C3C(C(C=C(O3)N4CCOCC4)=O)=C1
AZD8186 is a novel potent small molecule that targets the lipid kinase PI3Kβ with selectivity vs PI3Kα. AZD8186 reduces pAKT-S473 in the PTEN deficient MDA-MB-468 cell line with an IC50 <5nM, while in the PI3Kα-dependent PIK3CA mutant line BT474 it is 200 fold less potent. AZD8186 also demonstrates cellular activity versus PI3Kβ, inhibiting IgM-dependent pAKT-S473 with an IC50 of 15nM.
1: Barlaam B, Cosulich S, Degorce S, Fitzek M, Green S, Hancox U, Lambert-Van Der Brempt C, Lohmann JJ, Maudet M, Morgentin R, Pasquet MJ, Peru A, PlÃ© P, Saleh T, Vautier M, Walker M, Ward L, Warin N. Discovery of (R)-8-(1-(3,5-difluorophenylamino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chrom ene-6-carboxamide (AZD8186): A Potent and Selective Inhibitor of PI3Kβ and PI3Kδ for the treatment of PTEN-deficient cancers. J Med Chem. 2014 Dec 16. [Epub ahead of print] PubMed PMID: 25514658.
2: Hancox U, Cosulich S, Hanson L, Trigwell C, Lenaghan C, Ellston R, Dry H, Crafter C, Barlaam B, Fitzek M, Smith PD, Ogilvie D, D'Cruz C, Castriotta L, Wedge SR, Ward L, Powell S, Lawson M, Davies BR, Harrington EA, Foster E, Cumberbatch M, Green S, Barry ST. Inhibition of PI3Kβ signaling with AZD8186 inhibits growth of PTEN deficient breast and prostate tumour alone and in combination with docetaxel. Mol Cancer Ther. 2014 Nov 14. pii: molcanther.0406.2014. [Epub ahead of print] PubMed PMID: 25398829.
3: Marques RB, Aghai A, de Ridder CM, Stuurman D, Hoeben S, Boer A, Ellston RP, Barry ST, Davies BR, Trapman J, van Weerden WM. High Efficacy of Combination Therapy Using PI3K/AKT Inhibitors with Androgen Deprivation in Prostate Cancer Preclinical Models. Eur Urol. 2014 Sep 11. pii: S0302-2838(14)00806-9. doi: 10.1016/j.eururo.2014.08.053. [Epub ahead of print] PubMed PMID: 25220373.