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 is a dual PI3K and mTOR kinase inhibitor, characterized as an imidazoquinoline with specific substitutions that contribute to its pharmacological properties. It is a light beige solid that has been developed for cancer treatment, showing potential in inhibiting both solid tumors and metastatic melanoma.

Uses

Used in Oncology:
NVP-BEZ235 is used as an inhibitor of phosphatidylinositol 3-kinases (PI3K) and mTOR, playing a crucial role in controlling gene expression related to cell proliferation, differentiation, and apoptosis. Its increased activity is significant in many types of cancer, making it a potent therapeutic agent.
Used in Anticancer Drug Combinations:
NVP-BEZ235 is used in combination with other anticancer agents to enhance their efficacy. It is well-tolerated when administered orally and can lead to disease stasis, making it a valuable component in cancer treatment regimens.
Used in Angiogenesis Inhibition:
As a potent inhibitor of VEGF-induced angiogenesis, NVP-BEZ235 is used to prevent the formation of new blood vessels that supply nutrients to tumors, thereby inhibiting their growth.
Used in Overcoming Drug Resistance:
NVP-BEZ235 is used to reverse lapatinib resistance, a significant issue in cancer treatment where tumors become resistant to certain drugs, thus broadening the scope of effective treatments.
Used in Cancer Cell Cycle Arrest:
NVP-BEZ235 induces G1 arrest and reduces cyclin D1 expression in melanoma cells, effectively halting the cell cycle and preventing uncontrolled cell growth.
Used in Targeting Cancer Cells with PI3K Mutations:
NVP-BEZ235 is used to inhibit the growth of cancer cells with activating PI3K mutations, providing a targeted approach to treating specific types of cancer.
Used in In Vivo Cancer Treatment:
NVP-BEZ235 has demonstrated activity in vivo, making it a promising candidate for further research and development 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 
• 915019-53-3 2-(4-(8-bromo-2-oxo-2,3-dihydro-1H-imidazo[4,5-c]quinolin-1-yl)phenyl)-2-methylpropanenitrile 
• 853908-49-3 5-bromo-2-((2-nitroethenyl)amino)benzoic acid 
• 915019-52-2 2-[4-(3-amino-6-bromo-quinolin-4-ylamino)-phenyl]-2-methyl-propionitrile 
• 915019-51-1 2-(4-((6-bromo-3-nitroquinolin-4-yl)amino)phenyl)-2-methylpropanenitrile 
• 115279-57-7 2-(4-aminophenyl)-2-methylpropionitrile 
• 71825-51-9 4-(2-cyanoprop-2-yl)-1-nitrobenzene 
• 723281-72-9 6-bromo-4-chloro-3-nitroquinoline 
• 853908-50-6 6-bromo-3-nitroquinolin-4-ol 

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.