To construct three final KRAS libraries, an equimolar pool of single mutants of each block and wild type were used as the plasmid template for a round of nicking mutagenesis. The mutants were chosen based on their varying binding affinities to RAF1 (refs.18,19), ensuring a range of affiniti...
wild-type andmutant proteinforms. Because of its high specificity in distinguishing molecular mass,mass spectrometryhas been applied to detect the wild-type and mutantKRASproteins in pancreatic tumor tissue, cells, and cyst fluids[73–75]. Stable isotope-labeled synthetic reference peptides ...
The overexpression of wild-type KRAS significantly stimulated cell migration, which is further promoted by KRAS (G12V) [54, 55]. Combined, the observations of these resistance mechanisms help to develop new combination therapeutics overcoming clinical drug resistance [53]. In conclusion, the possible...
Indeed, mixing a 15 nM solution of the unstructured αH-His2 in absence of Pd(II) with increasing concentrations of wild-type KRASwt did not produce any increase in the fluorescence anisotropy of the TMR fluorophore at 559 nm, indicating that the apopeptide, αH-His2, has low ...
Vitamin C treatment selectively kills mutant KRAS expressing tumor cells, but not wild-type KRAS containing cells [27]. Interestingly, either glucose withdrawal or glucose-mediated hyperactivation of RAS is able to trigger apoptosis [26, 28]. RAS oncogenes trigger apoptosis only under specific ...
Compare the Structure of KRASG12Dco-crystallization with MRTX1133 (7RPZ, PDB), the green strucuture is PDB ID 7RPZ and the cyan is data from Medicilon. The data are very correlated. KRAS-G12D with MRTX1133 Structure of KRASG12Dco-crystallized with MRTX1133 with GDP-bound ...
Reports at scientific meetings are emerging with regard to preclinical inhibitors which selectively target the KRAS-G12D allele [48], such as MRTX-1133 (Mirati company presentation online) as well as pan-KRAS inhibitors [48] which address all the major KRAS mutants and wild-type KRAS but spare...
Phase II study of gemcitabine, oxaliplatin in combination with panitumumab in KRAS wild-type unresectable or metastatic biliary tract and gallbladder cancerBackground: Current data suggest that platinum-basThe British journal of cancer
a Intrinsic nucleotide-exchange curves of wild-type (WT) and mutant KRAS obtained from real-time NMR experiments. A tenfold molar excess of GTPγS was added to GDP-loaded KRAS at t = 0 and the GDP-bound fraction remaining was monitored over time by NMR. The data were fit to one...
The GQ-deficient constructs (GQ-null) were further created over respective wild-type templates (Promoter+GQ) via overlap-extension PCR techniques using mutagenic primers (Table S6). In short, the first round PCR reaction was carried out using the mutagenic (mut) primers and all the PCR...