A5072649527- Synthesis and Biological Evaluation
- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Synthetic Organic Chemistry Methods
- Asymmetric Synthesis and Catalysis
- Microbial Natural Products and Biosynthesis
- Marine Sponges and Natural Products
- Cancer, Hypoxia, and Metabolism
- Cancer Treatment and Pharmacology
- Catalytic Cross-Coupling Reactions
- Angiogenesis and VEGF in Cancer
- Receptor Mechanisms and Signaling
- Advanced Synthetic Organic Chemistry
- Click Chemistry and Applications
- Microtubule and mitosis dynamics
- Marine Biology and Environmental Chemistry
- Photosynthetic Processes and Mechanisms
- Chemical Synthesis and Analysis
- Marine Toxins and Detection Methods
- Asymmetric Hydrogenation and Catalysis
- Organic Chemistry Synthesis Methods
- Chemical Synthesis and Reactions
- Adrenal and Paraganglionic Tumors
Eisai (United States)
2016-2024
Mersana Therapeutics (United States)
2018-2024
Northwestern University
2005-2013
Boston College
2010
Yale University
2009
Northwest University
2005-2008
The total synthesis and structural revision of the marine natural product neopeltolide is reported. key bond-forming step involves a Lewis acid-catalyzed intramolecular cyclization to install tetrahydropyran ring macrocycle simultaneously. This type first its kind assembles carbon backbone efficiently. reported structure revealed differences in data between synthetic material. After significant investigation, diastereomeric molecule with C11 C13 configurations inverted was synthesized using...
The total synthesis and biological evaluation of neopeltolide analogs are reported. key bond-forming step utilizes a Lewis acid-catalyzed intramolecular macrocyclization that installs the tetrahydropyran ring macrocycle simultaneously. Independent each other, neither macrolide nor oxazole side chain substituents can inhibit growth cancer cell lines. data indicate alterations to either ester or stereochemistry result in loss activity.
A scandium triflate catalyzed, diastereoselective cyclization between aldehydes and β-hydroxy dioxinones has been discovered. This process capitalizes on the untapped nucleophilicity of embedded enol ether within dioxinone core. The bicyclic compounds from resulting can be isolated, or alternatively, alkoxide nucleophiles directly added. in situ addition fragments rings delivers 3-carboxy-substituted tetrahydropyran-4-ones good yields with high levels diastereoselectivity.
All things converge: A highly convergent synthesis of (−)-okilactomycin utilizes a Prins-type Maitland–Japp cyclization for the fragment assembly two complex intermediates (see scheme). The also employs diastereoselective Lewis acid promoted Diels–Alder reaction and an olefin ring-closing metathesis to close strained 11-membered macrocycle.
The Pd-catalyzed addition of organozinc reagents to unsaturated carbonyls in the presence carbon monoxide provides 1,4-diketones good yield. reaction was studied with a number substituted cyclic and acyclic ketones as well α,β-unsaturated aldehydes.
Chlorotoxin (Cltx) isolated from scorpion venom is an established tumor targeting and antiangiogenic peptide. Radiolabeled Cltx therapeutic (131I-TM601) yielded promising results in human glioma clinical studies, the imaging agent tozuleristide, under investigation CNS cancer studies. Several binding targets have previously been proposed for but none effectively explain its pleiotropic effects; true target remains ambiguous focus of this study. A peptide-drug conjugate (ER-472) composed...
Eine konvergente Synthese von (−)-Okilactomycin nutzt eine Prins-Maitland-Japp-Cyclisierung zur Verknüpfung zweier komplizierter Zwischenstufen (siehe Schema). Außerdem kam hoch diastereoselektive Lewis-Säure-vermittelte Diels-Alder-Reaktion zum Einsatz, und Olefin-Ringschlussmetathese ergab den gespannten 11-gliedrigen Makrocyclus. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents peer-reviewed, but not copy-edited or typeset. They...
Abstract Although microtubule inhibitors (MTI) remain a therapeutically valuable payload option for antibody–drug conjugates (ADC), some cancers do not respond to MTI-based ADCs. Efforts fill this therapeutic gap have led recent expansion of the ADC “toolbox” include payloads with novel mechanisms action such as topoisomerase inhibition and DNA cross-linking. We present here development mono-alkylator platform that exhibits sustained tumor growth suppression at single doses in MTI-resistant...
<div>Abstract<p>Although microtubule inhibitors (MTI) remain a therapeutically valuable payload option for antibody–drug conjugates (ADC), some cancers do not respond to MTI-based ADCs. Efforts fill this therapeutic gap have led recent expansion of the ADC “toolbox” include payloads with novel mechanisms action such as topoisomerase inhibition and DNA cross-linking. We present here development mono-alkylator platform that exhibits sustained tumor growth suppression at single...
<p>Table shows Tabulated cell growth inhibition data for NCI-N87 and MDA-MB231 cells in monoculture coculture when treated with ADCs T-16, T-17, T-18</p>
<p>Figure shows Structures of Platforms 6, and 8-16</p>
<p>Supplementary Materials and Methods including Assays Synthetic Procedures</p>
<p>Figure shows In vitro activity of NaPi2b ADCs X-BG and X-19 payload 4 in the OVCAR3 cell line</p>
<p>Table shows Cytotoxicity Data for Platforms 18 vs 19</p>
<p>Table shows Tabulated cell growth inhibition data for NCI-N87 and MDA-MB231 cells in monoculture coculture when treated with ADCs T-16, T-17, T-18</p>
<p>Structures of PBD Platform 5 and AF-HPA 7 (known as Dolaflexin)</p>
<p>Figure shows Plasma stability comparing indole-linked ADC T-13 to N10-linked T-BH</p>
<p>Figure shows Efficacy in OVCAR-3 xenograft for A) targeted ADCs X-17 and X-19 B) their corresponding non-binding control NB-17 NB-19</p>
<p>Extinction coefficient used to determine DAR for ADCs</p>
<p>Table shows Payload in vitro potency various cell lines.</p>
<p>Figure shows Plasma stability comparing indole-linked ADC T-13 to N10-linked T-BH</p>
<p>Figure shows Cytotoxicity of Mesothelin ADCs M-16, M-17, and M-19 in NCI-N87 cell line</p>
<p>Figure shows Structures of Platforms 6, and 8-16</p>