John R. Butler
A5036377107- Cancer-related gene regulation
- Chemical synthesis and alkaloids
- Synthesis and Catalytic Reactions
- Alkaloids: synthesis and pharmacology
- Catalytic C–H Functionalization Methods
- Synthetic Organic Chemistry Methods
- Axial and Atropisomeric Chirality Synthesis
- Crystallization and Solubility Studies
- Renin-Angiotensin System Studies
- Ion channel regulation and function
- X-ray Diffraction in Crystallography
- Biochemical and Molecular Research
- Coordination Chemistry and Organometallics
- Enzyme function and inhibition
- Peptidase Inhibition and Analysis
- Pharmacological Receptor Mechanisms and Effects
- Phenothiazines and Benzothiazines Synthesis and Activities
- Chemical Reaction Mechanisms
- Cholinesterase and Neurodegenerative Diseases
- Cardiomyopathy and Myosin Studies
- Berberine and alkaloids research
- Congenital heart defects research
- Advanced Synthetic Organic Chemistry
- Marine Sponges and Natural Products
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
Casma Therapeutics (United States)
2025
Amgen (United States)
2024
California Institute of Technology
2022
The University of Texas Southwestern Medical Center
2011-2016
Southwestern Medical Center
2013-2016
University of San Diego
2003
One of the most robust synthetic lethal interactions observed in multiple functional genomic screens has been dependency on PRMT5 cancer cells with MTAP deletion. We report discovery clinical stage MTA-cooperative inhibitor AMG 193, which preferentially binds presence MTA and potent biochemical cellular activity MTAP-deleted across lineages. In vitro, inhibition induces DNA damage, cell cycle arrest, aberrant alternative mRNA splicing cells. human line patient-derived xenograft models, 193...
Because of its strong genetic validation, NaV1.7 has attracted significant interest as a target for the treatment pain. We have previously reported on number structurally distinct bicyclic heteroarylsulfonamides inhibitors that demonstrate high levels selectivity over other NaV isoforms. Herein, we report discovery and optimization series atropisomeric quinolinone sulfonamide [ Bicyclic compounds sodium channel their preparation . WO 2014201206, 2014 ] NaV1.7, which nanomolar inhibition...
The kibdelones are aromatic polyketide natural products featuring isoquinolinone and tetrahydroxanthone ring systems. They display potent cytotoxicity toward a range of human cancer cell lines. Here, we present an enantioselective total synthesis kibdelone C that utilizes Shi epoxidation to establish the absolute relative stereochemistry, acid-catalyzed cyclization form tetrahydroxanthone, C–H arylation complete hexacyclic skeleton.
<p>Supplementary Methods: SDMA Imaging Assay, ELISA, Immunohistochemistry</p>
<p>Supplementary Figure S6. AM-9747 treatment results in increased DNA damage and cellular senescence BxPC-3 cells</p>
<p>Supplementary Figure S8. AMG 193 treatment in BxPC-3 tumors does not affect circulating blood cells</p>
<p>Supplementary Figure S5. <i>In vitro</i> target validation, RNA-seq, and additional cell cycle data in WT MTAP-deleted tumor cells</p>
<p>Supplementary Figure S2. SPR AMG 193 competitive chaser experiment</p>
<p>Supplementary Figure S3. HCT116 isogenic pair validation</p>
<p>Supplementary Figure S1. SPR chaser characterization</p>
<p>Supplementary Figure S7. Time course SDMA analysis, CDX models versus AMG 193, and AM-9747 PDX trial</p>
<p>Supplementary Figure S10. AMG 193 and sotorasib combination is synergistic in the MIAPACA2 MTAP–deleted, KRAS G12C mutant cell line</p>
<p>Supplementary Figure S9. AMG 193 chemotherapy combinations are synergistic in the H292 MTAP-deleted NSCLC cell line</p>
<div>Abstract<p>One of the most robust synthetic lethal interactions observed in multiple functional genomic screens has been dependency on protein arginine methyltransferase 5 (PRMT5) cancer cells with <i>MTAP</i> deletion. We report discovery clinical stage MTA-cooperative PRMT5 inhibitor AMG 193, which preferentially binds presence MTA and potent biochemical cellular activity MTAP-deleted across lineages. <i>In vitro</i>, inhibition induces DNA damage,...
<p>Supplementary Figure S11: AMG 193 treatment of patients with MTAP-deleted cancers results in inhibition serum SDMA</p>
<p>Supplementary Figure S4. AM-9747 preferentially inhibits viability and SDMA signaling in MTAP-deleted tumor cells</p>