915019-65-7

Basic information

• Product Name: NVP-BEZ 235
• Synonyms: 2-methyl-2-(3-methyl-2-oxo-8-(quinolin-3-yl)-2,3-dihydroimidazo[4,5-c]quinolin-1-yl)propanenitrile;2-Methyl-2-[3-Methyl-2-oxo-8-(3-quinolinyl)-1-iMidazo[4,5-c]quinolinyl]propanenitrile;4-[2,3-Dihydro-3-Methyl-2-oxo-8-(quinolin-3-yl)-1H-iMidazo[4,5-c]quinolin-1-yl]-alpha,alpha-diMethylbenzeneacetonitrile;BEZ-235;4-[2,3-Dihydro-3-Methyl-2-oxo-8-(3-quinolinyl)-1H-iMidazo[4,5-c]quinolin-1-yl]-α,α-diMethyl-benzeneacetonitrile;NVP-BEZ235(BEZ235);BEZ235 (NVP-BEZ235, Dactolisib);2-Methyl-2-(4-(3-methyl-2-oxo-8-(quinolin-3-yl)-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl)phenyl
• CAS NO: 915019-65-7
• Molecular Formula: C30H23N5O
• Molecular Weight: 469.54
• EINECS: 1312995-182-4
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Protein Kinase Inhibitors and Activators;api;Inhibitors;Akt;mTOR;PI3K
• Mol File: 915019-65-7.mol
• Article Data: 7

Chemical Properties

• Melting Point: 288-289°C
• Boiling Point: 701.025 °C at 760 mmHg
• Flash Point: 377.767 °C
• Appearance: /
• Density: 1.299
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.705
• Storage Temp.: Refrigerator
• Solubility: Soluble in DMSO (up to 1 mg/ml with warming) or in DMF (up to 10 mg/ml, dissolves slowly, requires heating to 75?C).
• PKA: 6.41±0.20(Predicted)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO or DMF may be stored at -20° for up to 1 month.
• CAS DataBase Reference: NVP-BEZ 235(CAS DataBase Reference)
• NIST Chemistry Reference: NVP-BEZ 235(915019-65-7)
• EPA Substance Registry System: NVP-BEZ 235(915019-65-7)

Safety Data

• Hazardous Substances Data: 915019-65-7(Hazardous Substances Data)

Usage

Description

NVP-BEZ235 (915019-65-7) is a dual PI3K and mTOR kinase inhibitor.1?It inhibits VEGF-induced proliferation and angiogenesis.2?Reverses lapatinib resistance.3?It induces G1 arrest and reduces cyclin D1 expression in melanoma cells with negligible apoptosis.4?NVP-BEZ235 inhibits the growth of cancer cells with activating PI3K mutations.5?The ability of NVP-BEZ235 to inhibit PI3K has come into question. This study also shows it to be a potent inhibitor of PRKDC (IC50 = 29 nM), ATM (IC50 = 13 nM), and ATR (IC50 = 8 nM).6?Active in vivo.

Chemical Properties

Light Beige Solid

Uses

Different sources of media describe the Uses of 915019-65-7 differently. You can refer to the following data:
1. Inhibitor of phosphatidylinositol 3-kinases, P13K and mTOR.
2. Phosphatidylinositol 3-kinase (PI3K) signaling through Akt/PKB and the mammalian target of rapamycin (mTOR) controls gene expression related to cell proliferation, differentiation, and apoptosis. Increased activity of this pathway is important in many types of cancer. NVP-BEZ235 is a potent dual inhibitor of PI3K and mTOR that is well tolerated, displays disease stasis when administered orally, and enhances the efficacy of other anticancer agents when used in in vivo combination studies. It inhibits PI3K isoforms and mutants with low nanomolar IC50 values, leading to growth arrest in the G1 phase. Through its effects on PI3K, NVP-BEZ235 inhibits VEGF-induced angiogenesis. By directly blocking cell growth and indirectly inhibiting angiogenesis, it has potential in both solid tumors and in metastatic melanoma therapy.[Cayman Chemical]

Definition

ChEBI: An imidazoquinoline that is 3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinoline substituted at position 1 by a 4-(1-cyanoisopropyl)phenyl group and at position 8 by a quinolin-3-yl group. A dual PI3K/mTOR inhibitor used in cancer treatment.

in vivo

BEZ235 induced tumor regression (69%) without a statistically significant effect on weight gain. Taken together, these preliminary in vivo efficacy findings suggest that BEZ235 blocks disease progression when administered orally alone and enhances efficacy when combined with other anticancer drugs.

References

1) Maira et al. (2008), Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity; Mol. Cancer Ther., 7 1851 2) Schnell et al. (2008), Effects of the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 on the tumor vasculature: implications for clinical imaging; Cancer Res., 68 6598 3) Eichhorn et al. (2008), Phosphatidylinositol 3-kinase hyperactivation results in lapatinib resistance that is reversed by the mTOR/Phosphatidylinositol 3-kinase inhibitor NVP-BEZ235; Cancer Res., 68 9221 4) Marone et al. (2009), Targeting melanoma with dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors; Mol. Cancer Res., 7 601 5) Serra et al. (2008), NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations; Cancer Res., 68 8022 6) Reinecke?et al. (2019),?Chemoproteomic selectivity profiling of PIKK and PI3K kinase inhibitors; ACS Chem.Biol., 14?655

InChI:InChI=1/C30H23N5O/c1-30(2,18-31)22-9-11-23(12-10-22)35-28-24-15-19(21-14-20-6-4-5-7-25(20)32-16-21)8-13-26(24)33-17-27(28)34(3)29(35)36/h4-17H,1-3H3

Upstream product

• 915019-50-0 2-[4-(8-bromo-3-methyl-2-oxo-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]-2-methyl-propionitrile 
• 191162-39-7 quinolin-3-ylboronic acid 
• 853908-50-6 6-bromo-3-nitroquinolin-4-ol 
• 723281-72-9 6-bromo-4-chloro-3-nitroquinoline 
• 71825-51-9 4-(2-cyanoprop-2-yl)-1-nitrobenzene 
• 115279-57-7 2-(4-aminophenyl)-2-methylpropionitrile 
• 915019-51-1 2-(4-((6-bromo-3-nitroquinolin-4-yl)amino)phenyl)-2-methylpropanenitrile 
• 915019-52-2 2-[4-(3-amino-6-bromo-quinolin-4-ylamino)-phenyl]-2-methyl-propionitrile 
• 853908-49-3 5-bromo-2-((2-nitroethenyl)amino)benzoic acid 
• 915019-53-3 2-(4-(8-bromo-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl)phenyl)-2-methylpropanenitrile 

Relevant articles and documents

Development of a Robust Synthesis of Dactolisib on a Commercial Manufacturing Scale

The development of the robust synthesis of 2-methyl-2-[4-[3-methyl-2-oxo-8-(quinolin-3-yl)-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl]-phenyl]propionitrile (dactolisib) on a commercial scale is described. The key step is a Pd-catalyzed Suzuki coupling of 2-[4-(8-bromo-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl)-phenyl]-2-methyl-propionitrile to 3-quinoline boronic acid. A special focus is placed on reducing the amount of Pd catalyst used in the Suzuki coupling and purifying the crude drug substance, including removing traces of Pd.

COMPOUNDS AND METHOD FOR BLOCKING TRANSMISSION OF MALARIAL PARASITE

Disclosed are compounds of formula (I) and formula (II): (I) (II) wherein R1, R2, A, and B are as defined herein. Also disclosed is a method of blocking transmission of a Plasmodium parasite and a method of treating or preventing mal

JAK P13K/mTOR COMBINATION THERAPY

Provided herein is a combination therapy comprising a JAK kinase inhibitor and a dual PBK/mTOR inhibitor, as well as methods of treating various cancers through the use of such a combination therapy.