Recommanded Product: 4-Hydroxyquinolin-2(1H)-one. Recently I am researching about ACQUIRED-RESISTANCE; IN-VITRO; PROTEIN; DISCOVERY; DOCKING; PHOSPHORYLATION; ACTIVATION; PRODUCTS; QUINONES; BVD-523, Saw an article supported by the Cancer Prevention and Research Institute of Texas grant [RP160657]; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) – USA [R01 GM123252]; Welch FoundationThe Welch Foundation [F-1390]; Science and Technology Development Fund, STDF, EgyptScience and Technology Development Fund (STDF); NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) – USANIH National Institute of General Medical Sciences (NIGMS) [R01GM123252] Funding Source: NIH RePORTER. Published in ACADEMIC PRESS INC ELSEVIER SCIENCE in SAN DIEGO ,Authors: Aly, AA; El-Sheref, EM; Bakheet, MEM; Mourad, MAE; Brase, S; Ibrahim, MAA; Nieger, M; Garvalov, BK; Dalby, KN; Kaoud, TS. The CAS is 86-95-3. Through research, I have a further understanding and discovery of 4-Hydroxyquinolin-2(1H)-one
Approximately 60% of human cancers exhibit enhanced activity of ERK1 and ERK2, reflecting their multiple roles in tumor initiation and progression. Acquired drug resistance, especially mechanisms associated with the reactivation of the MAPK (RAF/MEK/ERK) pathway represent a major challenge to current treatments of melanoma and several other cancers. Recently, targeting ERK has evolved as a potentially attractive strategy to overcome this resistance. Herein, we report the design and synthesis of novel series of fused naphthofuro[3,2-c] quinoline-6,7,12-triones 3a-f and pyrano[3,2-c]quinoline-6,7,8,13-tetraones 5a,b and 6, as potential ERK inhibitors. New inhibitors were synthesized and identified by different spectroscopic techniques and X-ray crystallography. They were evaluated for their ability to inhibit ERK1/2 in an in vitro radioactive kinase assay. 3b and 6 inhibited ERK1 with IC50s of 0.5 and 0.19 mu M, and inhibited ERK2 with IC50s of 0.6 and 0.16 mu M respectively. Kinetic mechanism studies revealed that the inhibitors are ATP-competitive inhibitors where 6 inhibited ERK2 with a K-i of 0.09 mu M. Six of the new inhibitors were tested for their in vitro anticancer activity against the NCI-60 panel of tumor cell lines. Compound 3b and 6 were the most potent against most of the human tumor cell lines tested. Moreover, 3b and 6 inhibited the proliferation of the BRAF mutant A375 melanoma cells with IC50s of 3.7 and 0.13 mu M, respectively. In addition, they suppressed anchorage-dependent colony formation. Treatment of the A375 cell line with 3b and 6 inhibited the phosphorylation of ERK substrates p-90RSK and ELK-1 and induced apoptosis in a dose dependent manner. Finally, a molecular docking study showed the potential binding mode of 3b and 6 within the ATP catalytic binding site of ERK2.
About 4-Hydroxyquinolin-2(1H)-one, If you have any questions, you can contact Aly, AA; El-Sheref, EM; Bakheet, MEM; Mourad, MAE; Brase, S; Ibrahim, MAA; Nieger, M; Garvalov, BK; Dalby, KN; Kaoud, TS or concate me.. Recommanded Product: 4-Hydroxyquinolin-2(1H)-one
Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
,Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles