372196-67-3 Usage
Description
2-Methyl-5-nitro-1-benzenesulfonic acid 2-[(6-bromoimidazo[1,2-a]pyridin-3-yl)methylene]-1-methylhydrazide, also known as PIK-75, is a chemical compound that functions as a p110α inhibitor. It is an isoform-specific mutant at Ser773 and exhibits potent inhibitory effects on DNA-PK. 2-Methyl-5-nitro-1-benzenesulfonic acid 2-[(6-bromoimidazo[1,2-a]pyridin-3-yl)methylene]-1-methylhydrazide has potential applications in various industries due to its unique properties and ability to target specific biological processes.
Uses
Used in Pharmaceutical Industry:
PIK-75 is used as a pharmaceutical agent for the development of treatments targeting the p110α isoform of PI3K. Its isoform-specific inhibition at Ser773 and potent effect on DNA-PK make it a promising candidate for the treatment of various diseases, particularly those involving abnormal cell growth and proliferation.
Used in Cancer Research:
In cancer research, PIK-75 is employed as a tool compound to study the role of p110α and DNA-PK in tumor growth and progression. Its ability to inhibit these targets selectively allows researchers to investigate the underlying mechanisms of cancer development and identify potential therapeutic targets for the treatment of various malignancies.
Used in Drug Development:
PIK-75 is utilized in drug development as a lead compound for the design and synthesis of novel inhibitors targeting the p110α isoform of PI3K and DNA-PK. Its unique properties and inhibitory effects make it a valuable starting point for the development of new drugs with improved efficacy and selectivity.
Used in Biochemical Assays:
In biochemical assays, PIK-75 serves as a specific inhibitor of p110α and DNA-PK, enabling researchers to study the activity and function of these enzymes in various biological processes. Its use in these assays helps to elucidate the role of these targets in cellular signaling and their potential as therapeutic targets.
Overall, 2-Methyl-5-nitro-1-benzenesulfonic acid 2-[(6-bromoimidazo[1,2-a]pyridin-3-yl)methylene]-1-methylhydrazide, or PIK-75, is a versatile compound with potential applications in the pharmaceutical industry, cancer research, drug development, and biochemical assays. Its unique properties and inhibitory effects on p110α and DNA-PK make it a promising candidate for the development of novel treatments and research tools.
Enzyme inhibitor
This novel phosphoinositide-3 kinase p110α inhibitor (F.Wt. = 488.74; CAS 372196-67-3; Solubility (25°C): 98 mg/mL DMSO, <1 mg/mL Water), also known as (E)-N'-((6-bromoH-imidazo[1,2-a]pyridin-3-yl)methylene)-N,2- dimethyl-5-nitrobenzenesulfonohydrazide-HCl, competes with respect to a substrate (phosphatidylinositol, PI), unlike most other PI3K inhibitors, which bind at or near the ATP site. PIK-75 exhibits impressive isoform selectivity, with an IC50 value of 5.8 nM for p110α, while the corresponding IC50 values are 1300 nM, 76 nM and 510 nM for p110β, p110γ, and p110δ, respectively.
Check Digit Verification of cas no
The CAS Registry Mumber 372196-67-3 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 3,7,2,1,9 and 6 respectively; the second part has 2 digits, 6 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 372196-67:
(8*3)+(7*7)+(6*2)+(5*1)+(4*9)+(3*6)+(2*6)+(1*7)=163
163 % 10 = 3
So 372196-67-3 is a valid CAS Registry Number.
372196-67-3Relevant articles and documents
An Unusual Intramolecular Halogen Bond Guides Conformational Selection
Tesch, Roberta,Becker, Christian,Müller, Matthias Philipp,Beck, Michael Edmund,Quambusch, Lena,Getlik, Matth?us,Lategahn, Jonas,Uhlenbrock, Niklas,Costa, Fanny Nascimento,Polêto, Marcelo D.,Pinheiro, Pedro de Sena Murteira,Rodrigues, Daniel Alencar,Sant'Anna, Carlos Mauricio R.,Ferreira, Fabio Furlan,Verli, Hugo,Fraga, Carlos Alberto Manssour,Rauh, Daniel
, p. 9970 - 9975 (2018)
PIK-75 is a phosphoinositide-3-kinase (PI3K) α-isoform-selective inhibitor with high potency. Although published structure–activity relationship data show the importance of the NO2 and the Br substituents in PIK-75, none of the published studies could correctly determine the underlying reason for their importance. In this publication, we report the first X-ray crystal structure of PIK-75 in complex with the kinase GSK-3β. The structure shows an unusual U-shaped conformation of PIK-75 within the active site of GSK-3β that is likely stabilized by an atypical intramolecular Br???NO2 halogen bond. NMR and MD simulations show that this conformation presumably also exists in solution and leads to a binding-competent preorganization of the PIK-75 molecule, thus explaining its high potency. We therefore suggest that the site-specific incorporation of halogen bonds could be generally used to design conformationally restricted bioactive substances with increased potencies.
