900185-02-6

Basic information

• Product Name: PIK-294
• Synonyms: PIK-294;2-[[4-Amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-5-methyl-3-(2-methylphenyl)-4(3H)-quinazolinone;4(3H)-Quinazolinone, 2-[[4-aMino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyriMidin-1-yl]Methyl]-5-Methyl-3-(2-Methylphenyl)-;2-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-5-methyl-3-o-tolylquinazolin-4(3H)-one;2-((4-Amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-5-methyl-3-(o-tolyl)q
• CAS NO: 900185-02-6
• Molecular Formula: C28H23N7O2
• Molecular Weight: 489.54
• EINECS: -0
• Product Categories: Inhibitors;Akt;mTOR;PI3K
• Mol File: 900185-02-6.mol
• Article Data: 0

Chemical Properties

• Boiling Point: 790.4±70.0 °C(Predicted)
• Appearance: /
• Density: 1.43
• Storage Temp.: -20°C
• Solubility: ≥24.5 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH
• PKA: 8.95±0.10(Predicted)
• CAS DataBase Reference: PIK-294(CAS DataBase Reference)
• NIST Chemistry Reference: PIK-294(900185-02-6)
• EPA Substance Registry System: PIK-294(900185-02-6)

Safety Data

• RIDADR: UN 2811 6.1 / PGIII
• Hazardous Substances Data: 900185-02-6(Hazardous Substances Data)

Usage

Description

PIK-294 is a highly selective p110δ inhibitor with an IC50 of 10 nM, making it a potent and specific compound for targeting the p110δ isoform of phosphoinositide 3-kinase (PI3K). As a derivative of PIK-293 (P437700), PIK-294 demonstrates a significant level of selectivity, being 1000-, 49-, and 16-fold less potent to PI3Kα/β/γ, respectively.

Uses

Used in Pharmaceutical Industry:
PIK-294 is used as a research tool for studying the role of p110δ in various biological processes and diseases. Its high selectivity and potency make it a valuable compound for investigating the specific functions of the p110δ isoform in cellular signaling pathways and its potential as a therapeutic target.
Used in Cancer Research:
PIK-294 is used as a potential therapeutic agent for the treatment of cancer. The p110δ isoform of PI3K has been implicated in the development and progression of various cancers, making PIK-294 a promising candidate for the development of targeted cancer therapies. Its high selectivity for p110δ may help to minimize off-target effects and improve the safety and efficacy of treatment.
Used in Drug Development:
PIK-294 is used as a lead compound in the development of new drugs targeting the PI3K pathway. Its high selectivity and potency provide a strong foundation for the design and optimization of novel therapeutic agents that can modulate the activity of the p110δ isoform, potentially leading to more effective treatments for a range of diseases, including cancer.
Used in Cellular Signaling Research:
PIK-294 is used as a chemical probe to dissect the complex signaling networks regulated by the PI3K family of enzymes. By selectively inhibiting the p110δ isoform, researchers can gain insights into the specific roles of this enzyme in cellular processes and identify potential points of intervention for the development of targeted therapies.

Features

A p110δ inhibitor.

In vitro

PIK-294 shows distinct patterns of isoform selectivity to inhibit different subsets of class I PI3K isoforms (p110β, p110δ, and p110γ) and exhibits low sensitivity to p110α with IC50 of 10 μM). The m-phenol moiety of PIK-294 is able to penetrate the deep-affinity pocket of the ATP binding site, and thus increases in vitro inhibitory activity.

Biological Activity

pik-294 is a highly selective p110δ inhibitor, 1000-, 49- and 16-fold less potent to pi3kα/β/γ, respectively.phosphoinositide 3-kinases (pi3-ks) are a key emerging class of drug targets, but the unique roles of pi3-k isoforms remain rarely defined. their target selectivity was biochemically enumerated that revealed cryptic homologies across targets and chemotypes by synthesizing chemically diverse panel of pi3-k inhibitors. crystal structures of three inhibitors to p110g identify a conformationally mobile region that is uniquely exploited by bound selective compounds. this chemical array was then used to define the pi3-k isoforms required for insulin signaling.

Biochem/physiol Actions

PIK-294 is a highly selective inihibitor of the phosphoinositide 3-kinase (PI3K) p110δ with an IC50 value of 10 nM compared to IC50 values of 10 μM, 490 nM and 160 nM for PI3Kα/β/γ, respectively. PIK-294 has been used to help distinguish the unique roles of the various PI3-K isoforms. For example, in a study of CXCL8-induced neutrophil migration, PIK-294 inhibited both chemokinetic and chemotactic CXCL8-induced migration whereas PI3Kγ inhibitor AS-605240 markedly reduced CXCL8 induced chemokinetic migration but had no effect on CXCL8 induced chemotactic migration.

in vitro

pik-294 displays distinct patterns of isoform selectivity to inhibit different subsets of class i pi3k isoforms (p110β, p110δ, and p110γ) and shows low sensitivity to p110α with ic50 of 10 μm). the m-phenol moiety of pik-294 can penetrate the deep-affinity pocket of the atp binding site, and thus promotes in vitro inhibitory activity. pik-294 showed one of the most potent p110d-selective inhibitors reported at present.

in vivo

pik-294 bound p110a inhibits the acute effects of insulin treatment in vivo, whereas a p110b inhibitor has no effect.

references

[1] knight za, gonzalez b, feldman me, zunder er, goldenberg dd, williams o, loewith r, stokoe d, balla a, toth b, balla t, weiss wa, williams rl, shokat km, et al. . a pharmacological map of the pi3-k family defines a role for p110alpha in insulin signaling. cell. 2006 may 19;125(4):733-47. epub 2006 apr 27.[2] bobrovnikova-marjon e1, pytel d, riese mj, vaites lp, singh n, koretzky ga, witze es, diehl ja. perk utilizes intrinsic lipid kinase activity to generate phosphatidic acid, mediate akt activation, and promote adipocyte differentiation. mol cell biol. 2012 jun;32 (12):2268-78.