A5016241202- ATP Synthase and ATPases Research
- Biochemical and Molecular Research
- Cytokine Signaling Pathways and Interactions
- Synthesis and Reactions of Organic Compounds
- Phenothiazines and Benzothiazines Synthesis and Activities
- Synthesis and Biological Evaluation
- Synthesis of heterocyclic compounds
- Synthesis and Characterization of Heterocyclic Compounds
- Synthesis and Reactivity of Heterocycles
- Fluorine in Organic Chemistry
- Synthesis and biological activity
- Structural and Chemical Analysis of Organic and Inorganic Compounds
- Chemical Synthesis and Analysis
- Coordination Chemistry and Organometallics
- Chemical Synthesis and Reactions
- Organic Chemistry Cycloaddition Reactions
- Synthesis and pharmacology of benzodiazepine derivatives
- Protein Tyrosine Phosphatases
- Diatoms and Algae Research
- Inorganic and Organometallic Chemistry
- Chemical Reaction Mechanisms
- Crystal structures of chemical compounds
- Catalysis for Biomass Conversion
- Quinazolinone synthesis and applications
- Molecular Junctions and Nanostructures
Mirati Therapeutics (United States)
2024
BioCryst Pharmaceuticals (United States)
1996-1998
Rensselaer Polytechnic Institute
1972
KRAS is the most frequently mutated oncogene in human cancer and facilitates uncontrolled growth through hyperactivation of RTK/MAPK pathway. The Son Sevenless homolog 1 (SOS1) protein functions as a guanine nucleotide exchange factor (GEF) for RAS subfamily small GTPases represents druggable target Using structure-based drug discovery approach, MRTX0902 was identified selective potent SOS1 inhibitor that disrupts KRAS:SOS1 protein-protein interaction to prevent SOS1-mediated on translates...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMesoionic compounds. XX. Cycloaddition reactions of pyrylium betainesK. T. Potts, A. J. Elliott, and M. SormCite this: Org. Chem. 1972, 37, 24, 3838–3845Publication Date (Print):December 1, 1972Publication History Published online1 May 2002Published inissue 1 December 1972https://pubs.acs.org/doi/10.1021/jo00797a016https://doi.org/10.1021/jo00797a016research-articleACS PublicationsRequest reuse permissionsArticle Views232Altmetric-Citations37LEARN...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTo-Dibenzoyl heterocycles via cycloaddition reactions. Convenient route to fused pyridazine systemsK. T. Potts and A. J. ElliottCite this: Org. Chem. 1973, 38, 9, 1769–1770Publication Date (Print):May 1, 1973Publication History Published online1 May 2002Published inissue 1 1973https://pubs.acs.org/doi/10.1021/jo00949a044https://doi.org/10.1021/jo00949a044research-articleACS PublicationsRequest reuse permissionsArticle...
A synthesis of 4H-1,3,4-benzoxadiazines [(V) and (VI)] from N-aroyl-N′-acetyl-N′-(2,4-dihalogenophenyl)-hydrazines is described. The process involves displacement ortho-halogen, fluorine being more readily displaced than bromine; in some cases a smooth deacetylation [(V)→(VI)] follows ring closure. 7-nitro-4H-1,3.4-benzoxadiazine hydrazonyl bromide reported.
Abstract Die Verbindungen (I) und (II) cyclisieren zu den Imidazopyridinen (III), von denen (IV) als Antiulcusmittel für die klinische Erprobung ausgewählt wird.
<p>Supplementary Figure S6 details the improved antiproliferative activity observed with MRTX0902/osimertinib combination in EGFR mutant models, PC9 (EGFR ex19del) and NCI-H1975 L858R/T790M).</p>
<p>Supplementary Materials and Methods section includes detailed protocols for the following: Experimental Preparation of MRTX0902 Avutometinib, SOS1 Biochemical Binding Assay, SOS2 Functional Assays, KRAS-SOS1 Protein-Protiein Interaction (PPI) HTRF In-Cell Western 3D Ultra-Low Attachment (ULA) Viability Immunoblotting Densitometry Analysis, DUSP6 Quantification from Naive Tumor-Bearing Mouse Blood, Bioanalysis Pharmacokinetic Synergy CRISPR/Cas9 Screening Data Analysis Methodology,...
<p>Supplementary Figure S5 shows levels of KRAS-MAPK pathway modulation associated with coadministration MRTX0902 and adagrasib in the murine CT26 (KRAS G12C-mutant) model.</p>
<p>Supplementary Figure S2 shows the antitumor activity of MRTX0902 in LN229 (PTPN11 A72S-mutant) model, with tumor growth inhibition data displayed S2A and ERK phosphorylation graphed S2B.</p>
<div>Abstract<p><i>KRAS</i> is the most frequently mutated oncogene in human cancer and facilitates uncontrolled growth through hyperactivation of receptor tyrosine kinase (RTK)/mitogen-activated protein (MAPK) pathway. The Son Sevenless homolog 1 (SOS1) functions as a guanine nucleotide exchange factor (GEF) for RAS subfamily small GTPases represents druggable target Using structure-based drug discovery approach, MRTX0902 was identified selective potent SOS1...
<p>Supplementary Figure S7 shows the improved antiproliferative activity observed with MRTX0902/avutometinib combination in KRAS-MAPK pathway mutant models, LN229 (PTPN11 A72S) and NCI-H1435 (NF1 K615N).</p>
<p>Supplementary Figure S1 details the genetic vulnerabilities and modifiers of response associated with combination treatment MRTX0902 adagrasib in KRAS G12C-mutant MIA PaCa-2 (S1A, S1B, S1D, S1E) LU99 (S1C) cell lines <i>in vitro</i> vivo</i>.</p>
<p>Supplementary Figure S3 details the antitumor effects and gene set enrichment analysis data associated with coadministration of MRTX0902 adagrasib in KRAS G12C-mutant human tumor xenograft models.</p>
<p>Supplementary Figure S8 details the antitumor effects associated with coadministration of MRTX0902 and adagrasib in MIA PaCa-2 (KRAS G12C-mutant) model.</p>
<p>Supplementary Figure S4 shows levels of KRAS-MAPK pathway modulation associated with coadministration MRTX0902 and adagrasib in the MIA PaCa-2 (KRAS G12C-mutant) model.</p>
Abstract Benzoin (I) und Dibenzoylacetylen (II) reagieren in Gegenwart von Kaliumc bonat zu dem Furan (III), das zum 2,3‐Dibenzoyl‐4,5‐diphenyl‐furan (IV) dehydratisiert wird.
Abstract Beim Erhitzen in DMF Gegenwart von Triäthylamin cyclisieren sich die Hydrazide (I) unter Abspaltung der Acetylgruppe zu den Benzoxadiazinen (II), Derivaten (III) acetylieren lassen; im Gegensatz dazu erfolgt Cyclisierung (I)‐Analogen (IV) ohne Verlust Acetylgruppe, wobei Benzoxadiazine (V) gebildet werden.