Hutchmed (China) Limited (Hutchmed) has initiated a phase I study of HMPL-295, its investigative and highly selective oral inhibitor of ERK, which is a downstream component of the RAS-MAPK pathway signaling cascade. HMPL-295 has the potential to address intrinsic or acquired resistance from upst...
8. Collisson, E. A. et al. A central role for RAF→MEK→ERK signaling in the genesis of pancreatic ductal adenocarcinoma.Cancer Discov.2, 685–693 (2012). 9. Infante, J. R. et al. A randomised, double-blin...
CC-90003 is an irreversible inhibitor of ERK1/2 with IC50s in the 10-20 nM range and shows good kinase selectivity in a 258-kinase biochemical assay.
9. Infante, J. R. et al. A randomised, double-blind, placebo-controlled trial of trametinib, an oral MEK inhibitor, in combination with gemcitabine for patients with untreated metastatic adenocarcinoma of the pancreas. Eur. J. Cancer 50, 2072–2081 (2014)....
And the AKT and EKT hyperphosphorylation contributes to erlotinib resistance might provide the indica- tion of combination with AKT/EKT inhibitor in clinical erlotinib therapy. Moreover, our finding might also suggest a mechanism of secondary drug tolerance in patients treated with erlo- tinib, ...
9. Infante, J. R. et al. A randomised, double-blind, placebo-controlled trial of trametinib, an oral MEK inhibitor, in combination with gemcitabine for patients with untreated metastatic adenocarcinoma of the pancreas.Eur. J. Cancer50, 2072–2081 (2014). ...
Phase I clinical trials in pancreatic cancer in USA are underway as well. GDC-0994 (RG-7842, Genentech/Array) is a very potent dual inhibitor of ERK1/2 (with IC50's of 1.2 and 0.3 nmol/L, respectively). GDC-0994 has shown promising combination activity with cobimetinib in RAS-mutated ...
Clinical trialUlixertinibERK inhibitorDermatologic adverse eventsBackground Ulixertinib is the first-in-class ERK1/2 kinase inhibitor with encouraging clinical activity in BRAF- and NRAS- mutant cancers. Dermatologic adverse events (dAEs) are common with ulixertinib, so management guidelines like ...
Discovery of (S)-1-(1-(4-Chloro-3-fluorophenyl)-2-hydroxyethyl)-4-(2-((1-methyl-1H-pyrazol-5-yl)amino)pyrimidin-4-yl)pyridin-2(1H)-one (GDC-0994), an Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Inhibitor in Early Clinical Developme [Content Brief] [2]. Kirk Robarge, ...
8.wilmottjs,tembev,howlejr,etal.intratumoralmolecularheterogeneityinabraf-mutant,brafinhibitor-resistantmelanoma:acaseillustratingthechallengesforpersonalizedmedicine.molcancerther.2012;11(12):2704-2708. 9.vanallenem,waglen,suckera,etal.thegeneticlandscapeofclinicalresistancetorafinhibitioninmetastaticmelanoma.canc...