1173204-81-3

Basic information

• Product Name: PKI-402
• Synonyms: 1-[4-[3-Ethyl-7-(morpholin-4-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl]phenyl]-3-[4-[(4-methylpiperazin-1-yl)carbonyl]phenyl]urea;1-(4-(3-ethyl-7-morpholino-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)phenyl)-3-(4-(1-methylpiperazine-4-carbonyl)phenyl)urea;1-(4-(3-ethyl-7-morpholino-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)phenyl)-3-(4-(4-methylpiperazine-1-carbonyl)phenyl)urea;1-(4-(3-Ethyl-7-morpholino-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)phenyl)-3-(4-(4-methylpiper
• CAS NO: 1173204-81-3
• Molecular Formula: C₂₉H₃₄N₁₀O₃
• Molecular Weight: 570.64546
• Product Categories: PI3K/Akt/mTOR;Akt;mTOR;PI3K
• Mol File: 1173204-81-3.mol

Chemical Properties

• Boiling Point: 670.6±55.0 °C(Predicted)
• Appearance: /
• Density: 1.43
• Solubility: insoluble in EtOH; insoluble in H2O; ≥14.28 mg/mL in DMSO
• PKA: 13.80±0.70(Predicted)
• CAS DataBase Reference: PKI-402(CAS DataBase Reference)
• NIST Chemistry Reference: PKI-402(1173204-81-3)
• EPA Substance Registry System: PKI-402(1173204-81-3)

Safety Data

• Hazardous Substances Data: 1173204-81-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
PKI-402 is used as a potential antitumor drug for its ability to inhibit the PI3K/mTOR signaling pathway, which plays a crucial role in cell growth, proliferation, and survival. Its dual inhibition of PI3K and mTOR makes it a promising candidate for the treatment of various cancer types.
Used in Cancer Research:
PKI-402 is used as a research tool in cancer biology to study the role of the PI3K/mTOR pathway in tumor growth, progression, and resistance to therapy. Its high selectivity and potency allow researchers to investigate the specific effects of inhibiting this pathway on different cancer cells and explore potential therapeutic strategies.

Biological Activity

pki-402 is a selective, equipotent and atp-competitive class i pi3k inhibitor (ic50= 1 nm, 7 nm, 16 nm and 14 nm for pi3kα, pi3kβ, pi3kγ and pi3kδ, respectively.)pi3k (phosphatidylinositol-4,5-bisphosphate 3-kinase) is a family of enzymes involved in cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking, which in turn are involved in cancer. it plays a key role in pi3k/akt/mtor pathway.in multiple human cancer cell lines (e.g. breast, brain, pancreas and nscl), pki-402 inhibited growth of cancer cells, and attenuated phosphorylation of effector of pi3k and mtor. in mda-mb-361, 30 nm pki-402 caused cleaved of the apoptosis marker—parp.in mda-mb-361 mouse tumor xenograft models, administration of 100 mg/kg of pki-402 daily for 5 days decreased the initial tumor volume from 260 mm3 to 129 mm3 and inhibited tumor regrowth for 70 days, single dose of pki-402 blocked phosphorylation of akt and led to cleaved parp.1. mallon r, hollander i, feldberg l et al. antitumor efficacy profile of pki-402, a dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor. mol cancer ther. 2010 apr;9(4):976-84.

Upstream product

• 109-01-3 1-methyl-piperazine 
• 1173204-78-8 4-({[4-(3-ethyl-7-morpholin-4-yl-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)phenyl]carbamoyl}amino)benzoic acid 

Relevant articles and documents

Lead optimization of n-3-substituted 7-morpholinotriazolopyrimidines as dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors: Discovery of PKI-402

Herein we describe the identification and lead optimization of triazolopyrimidines as a novel class of potent dual PI3K/mTOR inhibitors, resulting in the discovery of 3 (PKI-402). Compound 3 exhibits good physical properties and PK parameters, low nanomolar potency against PI3KR and mTOR, and excellent inhibition of cell proliferation in several human cancer cell lines. Furthermore, in vitro and in vivo biomarker studies demonstrated the ability of 3 to shut down the PI3K/Akt pathway and induce apoptosis in cancer cells. In addition, 3 showed excellent in vivo efficacy in various human cancer xenografts, validating suppression of PI3K/mTOR signaling as a potential anticancer therapy. 2009 American Chemical Society.

3H-[1,2,3]TRIAZOLO[4,5-D]PYRIMIDINE COMPOUNDS, THEIR USE AS mTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES

The invention relates to 3H-[1,2,3]triazolo[4,5-d]pyrimidine compounds of the Formula 1: or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.