183793-49-9Relevant articles and documents
Discovery of a Potent and Selective Oral Inhibitor of ERK1/2 (AZD0364) That Is Efficacious in Both Monotherapy and Combination Therapy in Models of Nonsmall Cell Lung Cancer (NSCLC)
Ward, Richard A.,Anderton, Mark J.,Bethel, Paul,Breed, Jason,Cook, Calum,Davies, Emma J.,Dobson, Andrew,Dong, Zhiqiang,Fairley, Gary,Farrington, Paul,Feron, Lyman,Flemington, Vikki,Gibbons, Francis D.,Graham, Mark A.,Greenwood, Ryan,Hanson, Lyndsey,Hopcroft, Philip,Howells, Rachel,Hudson, Julian,James, Michael,Jones, Clifford D.,Jones, Christopher R.,Li, Yongchao,Lamont, Scott,Lewis, Richard,Lindsay, Nicola,McCabe, James,McGuire, Thomas,Rawlins, Philip,Roberts, Karen,Sandin, Linda,Simpson, Iain,Swallow, Steve,Tang, Jia,Tomkinson, Gary,Tonge, Michael,Wang, Zhenhua,Zhai, Baochang
, p. 11004 - 11018 (2019)
The RAS/MAPK pathway is a major driver of oncogenesis and is dysregulated in approximately 30% of human cancers, primarily by mutations in the BRAF or RAS genes. The extracellular-signal-regulated kinases (ERK1 and ERK2) serve as central nodes within this pathway. The feasibility of targeting the RAS/MAPK pathway has been demonstrated by the clinical responses observed through the use of BRAF and MEK inhibitors in BRAF V600E/K metastatic melanoma; however, resistance frequently develops. Importantly, ERK1/2 inhibition may have clinical utility in overcoming acquired resistance to RAF and MEK inhibitors, where RAS/MAPK pathway reactivation has occurred, such as relapsed BRAF V600E/K melanoma. We describe our structure-based design approach leading to the discovery of AZD0364, a potent and selective inhibitor of ERK1 and ERK2. AZD0364 exhibits high cellular potency (IC50 = 6 nM) as well as excellent physicochemical and absorption, distribution, metabolism, and excretion (ADME) properties and has demonstrated encouraging antitumor activity in preclinical models.
Biosurfactants from Marine Cyanobacteria Collected in Sabah, Malaysia
Matsuda, Fuyuhiko,Mehjabin, Jakia Jerin,Morikawa, Masaaki,Okino, Tatsufumi,Petitbois, Julie G.,Umezawa, Taiki,Vairappan, Charles S.,Wei, Liang
supporting information, (2020/06/08)
Chemical investigation of the organic extract from Moorea bouillonii, collected in Sabah, Malaysia, led to the isolation of three new chlorinated fatty acid amides, columbamides F (1), G (2), and H (3). The planar structures of 1-3 were established by a combination of mass spectrometric and NMR spectroscopic analyses. The absolute configuration of 1 was determined by Marfey's analysis of its hydrolysate and chiral-phase HPLC analysis after conversion and esterification with Ohrui's acid, (1S,2S)-2-(anthracene-2,3-dicarboximido)cyclohexanecarboxylic acid. Compound 1 showed biosurfactant activity by an oil displacement assay. Related known fatty acid amides columbamide D and serinolamide C exhibited biosurfactant activity with critical micelle concentrations of about 0.34 and 0.78 mM, respectively.
DIHYDROIMIDAZOPYRAZINONE DERIVATIVES USEFUL IN THE TREATMENT OF CANCER
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Page/Page column 141; 142, (2017/07/05)
The present disclosure concerns compounds of Formula (I) or pharmaceutically-acceptable salts thereof, wherein R1, R2 and R3 have any of the meanings defined hereinbefore in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of cancer.
