Home PI3K/Akt/mTOR PI3K inhibitor A66 For research use only.

A66

A66 is a potent and specific p110α inhibitor with IC50 of 32 nM in a cell-free assay, >100 fold selectivity for p110α over other class-I PI3K isoforms.

A66 Chemical Structure

A66 Chemical Structure

CAS No. 1166227-08-2

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A66 Related Products

Signaling Pathway

PI3K Signaling Pathways

PI3K Signaling Pathway

Biological Activity

Description A66 is a potent and specific p110α inhibitor with IC50 of 32 nM in a cell-free assay, >100 fold selectivity for p110α over other class-I PI3K isoforms.
Features Highly selective for the p110α isoform.
Targets
p110α [1]
(Cell-free assay)		 PI4Kβ [1]
(Cell-free assay)		 C2β [1]
(Cell-free assay)		 p110δ [1]
(Cell-free assay)
32 nM 236 nM 462 nM >1.25 μM
In vitro
In vitro In addition to the wild-type p110α, A66 also potently inhibits the oncogenic forms of p110α such as p110α E545K and p110α H1047R with IC50 of 30 nM and 43 nM, respectively. Unlike PIK-75, A66 displays >100 fold selectivity for p110α over other class-I PI3K isoforms. Among the class-II PI3Ks, class-III PI3K and PI4Ks, A66 only exhibits limited cross-reactivity with the class-II PI3K PI3KC2β and the PI4Kβ isoform of PI4K with IC50 of 462 nM and 236 nM, respectively. A66 exhibits no inhibitory activity against other lipid kinases or the related kinases DNA-PK and mTOR. A66 has a higher degree of specificity compared with PIK-75 when tested at 10 μM against two large panels of 110 protein kinases and 318 kinases. Inhibition of p110α alone by A66 treatment is sufficient to block insulin signalling to Akt/PKB in certain cell lines that harbor H1047R mutations in PIK3CA and have high levels of p110α and class-Ia PI3K activity. [1] A66 treatment at 0.7 μM induces a 75-80% reduction in focus formation by the highly transforming p85α iSH2 mutants KS459delN, DKRMN-S560del, and K379E, and reduces the phosphorylation of Akt on T308 by all p85 mutants. [2]
In Vivo
In vivo A single dose of A66 at 100 mg/kg induces a profound reduction in the phosphorylation of Akt/PKB and p70 S6 kinase, but not of ERK, in SK-OV-3 tumour tissue in vivo at both 1 hour and 6 hours after dosing. A66 dosed at 100 mg/kg once daily (QD) for 21 days or 75 mg/kg twice daily (BID) for 16 days induces a significant delay in growth of SK-OV-3 xenografted tumors with average TGI of 45.9% and 29.9%, respectively, which is even greater than that induced by the well-established pan-PI3K inhibitor BEZ-235. QD dosing of A66 in the HCT-116 xenograft model also induces a significant reduction in tumour volume with TGI of 77.2%, but causes a non-significant reduction in tumor volume in the U87MG xenograft model. [1] Administration of A66 at 10 mg/kg in male CD1 mice induces significant impairments in the ITT (insulin tolerance test) and GTT (glucose tolerance test), and an increase in glucose production during a PTT (pyruvate tolerance test), almost to the same level as the pan-PI3K inhibitors. [3]
Animal Research Animal Models Age-matched specific pathogen-free Rag1-/- or NIH-III mice inoculated subcutaneously with U87MG, SK-OV-3 or HCT-116 cells
Dosages 100 mg/kg once daily (QD) or 75 mg/kg twice daily (BID)
Administration Intraperitoneal injection
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01046383 Terminated
NON-SMALL CELL LUNG CANCER
Immunotec Inc.
 June 2010 Phase 3

Chemical Information & Solubility

Molecular Weight 393.53 Formula

C17H23N5O2S2
CAS No. 1166227-08-2 SDF Download A66 SDF
Smiles CC1=C(SC(=N1)NC(=O)N2CCCC2C(=O)N)C3=CSC(=N3)C(C)(C)C
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 79 mg/mL ( (200.74 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 1 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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