1166227-08-2 Usage
Description
(S)-N1-(2-(tert-butyl)-4'-methyl-[4,5'-bithiazol]-2'-yl)pyrrolidine-1,2-dicarboxamide, also known as A-66, is a potent and selective inhibitor of the PI3K isoform p110α with an IC50 of 32 nM in a cell-free assay. It exhibits over 100-fold selectivity for p110α compared to other isoforms. A-66 has demonstrated effectiveness in vivo, as it suppresses the growth of SK-OV-3 tumor xenografts in mice and impairs all measures of in vivo insulin action. Additionally, it partially suppresses B cell receptor-dependent Akt activation and proliferation.
Uses
Used in Pharmaceutical Industry:
A-66 is used as an inhibitor for the PI3K isoform p110α for its potent and selective action against this specific isoform. This makes it a valuable compound in the development of targeted therapies for various diseases, particularly those involving the PI3K/Akt/mTOR signaling pathway.
Used in Oncology Research:
In the field of oncology, A-66 is used as a research tool to study the role of the PI3K isoform p110α in tumor growth and progression. Its ability to suppress tumor growth in vivo makes it a promising candidate for further investigation into potential cancer treatments.
Used in Insulin Action Studies:
A-66 is utilized in research to understand the impact of PI3K isoform p110α inhibition on in vivo insulin action. Its impairment of all measures of in vivo insulin action in mice makes it a valuable tool for studying the relationship between PI3K signaling and insulin resistance or diabetes.
Used in B Cell Receptor Signaling Research:
A-66 is employed in the study of B cell receptor-dependent Akt activation and proliferation. Its partial suppression of these processes provides insights into the role of PI3K p110α in B cell signaling and the potential for targeted therapeutic intervention in related diseases.
Enzyme inhibitor
This potent and highly selective p110α inhibitor (FW = 393.53; CAS 1166227-08-2; Solubility: 79 mg/mL DMSO, 1 mg/mL H2O), also known as (2S)-N1-(5-(2-tert-butylthiazol-4-yl)-4-methylthiazol-2-yl)pyrrolidine-1, 2-dicarboxamide, has a IC50 value of 32 nM for the wild-type phosphoinositide-3 kinase p110 α as well as oncogenic forms of p110α such as p110α E545K (IC50 = 43 nM) and p110α H1047R (IC50 = 43 nM). A66 inhibition also demonstrated that cancer-specific mutations in the iSH2 (inter-SH2) and nSH2 (N-terminal SH2) domains of p85α, the regulatory subunit of phosphatidylinositide 3-kinase (PI3K), show gain of function, inducing oncogenic cellular transformation, stimulating cellular proliferation, and enhancing PI3K signaling.
Check Digit Verification of cas no
The CAS Registry Mumber 1166227-08-2 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,1,6,6,2,2 and 7 respectively; the second part has 2 digits, 0 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 1166227-08:
(9*1)+(8*1)+(7*6)+(6*6)+(5*2)+(4*2)+(3*7)+(2*0)+(1*8)=142
142 % 10 = 2
So 1166227-08-2 is a valid CAS Registry Number.
1166227-08-2Relevant articles and documents
Identification and optimisation of a 4′,5-bisthiazole series of selective phosphatidylinositol-3 kinase alpha inhibitors
Fairhurst, Robin A.,Imbach-Weese, Patricia,Gerspacher, Marc,Caravatti, Giorgio,Furet, Pascal,Zoller, Thomas,Fritsch, Christine,Haasen, Dorothea,Trappe, Joerg,Guthy, Daniel A.,Arz, Dorothee,Wirth, Jasmin
, p. 3569 - 3574 (2015/08/06)
Abstract Exploring the affinity-pocket binding moiety of a 2-aminothiazole (S)-proline-amide-urea series of selective PI3Kα inhibitors using a parallel-synthesis approach led to the identification of a novel 4′,5-bisthiazole sub-series. The synthesis and optimisation of both the affinity pocket and (S)-proline amide moieties within this 4′,5-bisthiazole sub-series are described. From this work a number of analogues, including 14 (A66) and 24, were identified as potent and selective PI3Kα inhibitor in vitro tool compounds.
