| Identification | Back Directory | [Name]
AZ 628 | [CAS]
878739-06-1 | [Synonyms]
CS-70
AZ-628
AZD628
AZ628/AZ-628
AZ628, >=99%
cas 878739-06-1
AZ-628;CAS 878739-06-1;AZ 628;AZ628
az628
DISCONTINUED, duplicate of A807000
3-(2-Cyanopropan-2-yl)-N-(4-methyl-3-((3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)amino)phenyl)
3-(2-Cyanopropan-2-yl)-N-(4-methyl-3-((3-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)amino)phenyl)ben
3-(2-cyanopropan-2-yl)-N-(4-methyl-3-(3-methyl-4-oxo-3,4-dihydroquinazolin-6-ylamino)phenyl)benzamide
3-(1-Cyano-1-methylethyl)-N-[3-[(3,4-dihydro-3-methyl-4-oxo-6-quinazolinyl)amino]-4-methylphenyl]benzamide
Benzamide, 3-(1-cyano-1-methylethyl)-N-[3-[(3,4-dihydro-3-methyl-4-oxo-6-quinazolinyl)amino]-4-methylphenyl]- | [Molecular Formula]
C27H25N5O2 | [MDL Number]
MFCD17392577 | [MOL File]
878739-06-1.mol | [Molecular Weight]
451.52 |
| Hazard Information | Back Directory | [Uses]
AZ 628 is an inhibitor of B-RAF and B-RAF(V600E) | [Definition]
ChEBI: 3-(2-cyanopropan-2-yl)-N-[4-methyl-3-[(3-methyl-4-oxo-6-quinazolinyl)amino]phenyl]benzamide is a member of benzamides. | [Biological Activity]
az628 is a potent and newly discorvered inhibitor of braf, c-raf-1 and brafv600e with ic50 values of 105 nm, 29 nm and 34 nm, respectively. this compound prevents craf activation through persistently occupying the atp-binding site of raf kinase. specificity profile suggests that az628 also inhibits activation of other tyrosine protein kinases such as ddr2, vegfr2, lyn, flt1, fms and others.raf kinases a family of three serine/threonine-specific protein kinases and participate in the ras-raf-mek-erk signal transduction cascade, also known as the mitogen-activated protein kinase (mapk) cascade. the activation of mapk signaling leads to different cellular response such as cell proliferation, apoptosis and inflammation.az628 has the potent anti-tumor activity. in human colon and melanoma-derived cell line that carries the recurrent v600e activating braf mutation, az628 was shown to inhibit anchorage-dependent and -independent growth, induce cell cycle arrest, and cause apoptosis [1]. az628 may be antiangiogenic due to inhibition of vegfr2 [2].generation of melanoma cell line clones is obtained resistance to the raf kinase inhibitor az628. resistance to az628 is connected with raised levels of the raf downstream effector p-erk1/2. erk1/2 initiation in az628-resistant clones is interceded by mek. supported multiplication of az628-resistant clones is to a great extent autonomous of braf kinase action. az628-resistant clones express elevated craf. survival of az628-safe cells is subject to craf [1]. | [in vitro]
AZ628 inhibits B-Raf, B-Raf AZ628 acts on B-Raf-containing M14 parental cell lines treated with increasing concentrations of AZ628, an effective inhibition of p-ERK1/2 levels was observed. It acts on AZ628-resistant M14 cells and does not inhibit ERK activation. AZ628 acts on NRAS-mutated malignant melanoma cells and effectively reduces ERK activation. | [Enzyme inhibitor]
This pan-Raf inhibitor (FW = 451.52 g/mol; CAS 878739-06-1; Solubility:
90 mg/mL DMSO, <1 mg/mL H2O), also named 3- (2-cyanopropan-2-yl) -
N- (4-methyl-3- (3-methyl-4-oxo-3,4-dihydroquinazolin-6-ylamino) -
phenyl) benzamide, targets the proto-oncogene B-Raf, or BRAF, or, more
formally, serine/threonine-protein kinase B-Raf (IC50 = 105 nM),
BRAFV600E (IC50 = 34 nM), and c-Raf-1 (IC50 = 29 nM), with off-target
inhibition of VEGFR2, DDR2, Lyn, Flt1, FMS, and others. Mechanism
of Action: Frequently mutated in human cancer, MAPK/ERK pathway
consists of a RAS family GTP protein that is activated in response to
extracellular signaling and recruits a RAF kinase family member to the cell
membrane. Once activated, RAF signals through MAP/ERK kinase to
activate ERK and its downstream effectors to regulate cell differentiation,
proliferation, senescence, and survival. Mutations in BRAF (especially
BRAFV600E) are found in approximately 30% of all human cancers
(melanoma, colorectal, and thyroid cancers), making the BRAF pathway a
druggable target for therapy. | [target]
| Target | Value | C-Raf-1
(Cell-free assay) | 29 nM | B-Raf (V600E)
(Cell-free assay) | 34 nM | B-Raf
(Cell-free assay) | 105 nM |
| [storage]
Store at -20°C | [References]
1. montagut c, sharma sv, shioda t, mcdermott u, ulman m, ulkus le, et al. elevated craf as a potential mechanism of acquired resistance to braf inhibition in melanoma. cancer res 2008,68:4853-4861.2. khazak v, astsaturov i, serebriiskii ig, golemis ea. selective raf inhibition in cancer therapy. expert opin ther targets 2007,11:1587-1609. |
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