A5033058750- Antimicrobial Resistance in Staphylococcus
- Orthopedic Infections and Treatments
- HIV/AIDS drug development and treatment
- Hepatitis C virus research
- Cancer therapeutics and mechanisms
- CRISPR and Genetic Engineering
- Advanced NMR Techniques and Applications
- Microtubule and mitosis dynamics
- Biochemical and Molecular Research
- Cancer Genomics and Diagnostics
- Acoustic Wave Resonator Technologies
- Radiopharmaceutical Chemistry and Applications
- Pneumocystis jirovecii pneumonia detection and treatment
- Synthesis of Organic Compounds
- Pneumonia and Respiratory Infections
- Microbial Natural Products and Biosynthesis
- Osteomyelitis and Bone Disorders Research
- Orthopaedic implants and arthroplasty
- Bioactive Compounds and Antitumor Agents
- Carbohydrate Chemistry and Synthesis
- PARP inhibition in cancer therapy
- Chemical Synthesis and Reactions
- Synthesis and Biological Evaluation
- Cancer-related Molecular Pathways
- Infectious Diseases and Tuberculosis
Vertex Pharmaceuticals (Canada)
2014
Aegera Therapeutics (Canada)
2008
Université de Montréal
2003
University of Iowa
1952
Amplification of the CCNE1 locus on chromosome 19q12 is prevalent in multiple tumour types, particularly high-grade serous ovarian cancer, uterine tumours and gastro-oesophageal cancers, where high cyclin E levels are associated with genome instability, whole-genome doubling resistance to cytotoxic targeted therapies
PKMYT1 is a regulator of CDK1 phosphorylation and compelling therapeutic target for the treatment certain types DNA damage response cancers due to its established synthetic lethal relationship with CCNE1 amplification. To date, no selective inhibitors have been reported this kinase that would allow investigation pharmacological role PKMYT1. address need compound 1 was identified as weak inhibitor. Introduction dimethylphenol increased potency on These analogs were found exist atropisomers...
Osteomyelitis is an infection located in bone and a notoriously difficult disease to manage, requiring frequent heavy doses of systemically administered antibiotics. Targeting antibiotics the after systemic administration may provide both greater efficacy treatment less administration. By taking advantage affinity bisphosphonate group for mineral, we have prepared set 13 bisphosphonated antibacterial prodrugs based on eight different linkers tethered free amino functionality fluoroquinolone...
Glycopeptides whose aminosugars have been modified by attachment of hydrophobic side chains are frequently active against vancomycin-resistant microorganisms. We compared the conformations six such fluorinated glycopeptides (with varying length) complexed to cell walls labeled with d-[1-13C]alanine, [1-13C]glycine, and l-[ε-15N]lysine in whole cells Staphylococcus aureus. The internuclear distances from 19F bound drug 13C 15N labels peptidoglycan, natural abundance 31P lipid membranes...
Benzoxazinorifamycins are potent antibacterial agents currently in development. Tethering these antibiotics to a bisphosphonate functional group by cleavable linker allows the delivery of osseous tissues, where they can be released over time treat bone infections. Various strategies presented herein develop osteotropic prodrugs, activities which examined vitro and vivo.
Enantiopure (3S,5R,8S)-3-[N-(Boc)amino]-1-azabicyclo[3.3.0]octan-2-one 8-carboxylic acid (1) was synthesized in nine steps and 16% overall yield from aspartate beta-aldehyde 7. Carbene-catalyzed acyloin condensation of 7, followed by acetylation samarium iodide reduction, gave linear precursor (2S,7S)-alpha,omega-diamino-4-oxosuberate 11, which converted to N-(Boc)aminopyrrolizidin-2-one carboxylic 1 a reductive amination/lactam cyclization sequence. X-ray analysis (3S,5R,8S)-methyl...
Abstract Amplification of the gene encoding cyclin E ( CCNE1 ) is an oncogenic driver in several malignancies and associated with chemoresistance poor prognosis. To uncover therapeutic targets for -amplified tumors, we undertook genome-scale CRISPR/Cas9-based synthetic lethality screens cellular models amplification. Here, report that increasing dosage engenders a vulnerability to inhibition PKMYT1 kinase, negative regulator CDK1. inhibit PKMYT1, developed RP-6306, orally bioavailable...
PKMYT1 is an important regulator of CDK1 phosphorylation and a compelling therapeutic target for the treatment certain types DNA damage response cancers due to its established synthetic lethal relationship with CCNE1 amplification. To date, no selective inhibitors have been reported this kinase that would allow investigation pharmacological role in cancer. address need we conducted focused screening effort identified compound 1 as weak inhibitor. Introduction dimethylphenol dramatically...
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