A5016700895- Monoclonal and Polyclonal Antibodies Research
- Chemical Synthesis and Analysis
- Peptidase Inhibition and Analysis
- Protein Structure and Dynamics
- Ovarian cancer diagnosis and treatment
- Protein Degradation and Inhibitors
- HER2/EGFR in Cancer Research
- Computational Drug Discovery Methods
- 14-3-3 protein interactions
- PI3K/AKT/mTOR signaling in cancer
- Cancer Mechanisms and Therapy
- Carbohydrate Chemistry and Synthesis
- Traditional and Medicinal Uses of Annonaceae
- Microtubule and mitosis dynamics
- Click Chemistry and Applications
- Estrogen and related hormone effects
- Ubiquitin and proteasome pathways
- Enzyme Structure and Function
- Cancer-related Molecular Pathways
- Synthetic Organic Chemistry Methods
- Protein Tyrosine Phosphatases
- Advanced biosensing and bioanalysis techniques
- Protein Kinase Regulation and GTPase Signaling
- Blood Coagulation and Thrombosis Mechanisms
- Sesquiterpenes and Asteraceae Studies
Athenex (United States)
2009-2022
University at Buffalo, State University of New York
2007-2016
Union Hospital
2013
Huazhong University of Science and Technology
2013
The University of Texas MD Anderson Cancer Center
2013
Obstetrics and Gynecology Hospital of Fudan University
2013
Philipps University of Marburg
2013
Tulane University
2012
Roswell Park Comprehensive Cancer Center
2009
Fox Chase Cancer Center
2009
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAn interactive computer graphics study of thermolysin-catalyzed peptide cleavage and inhibition by N-carboxymethyl dipeptidesDavid G. Hangauer, Arthur F. Monzingo, Brian W. MatthewsCite this: Biochemistry 1984, 23, 24, 5730–5741Publication Date (Print):November 1, 1984Publication History Published online1 May 2002Published inissue 1 November 1984https://doi.org/10.1021/bi00319a011RIGHTS & PERMISSIONSArticle Views462Altmetric-Citations204LEARN ABOUT...
The hydrophobic effect is associated with the successive replacement of water molecules in binding site a protein by groups ligand. Although assumed to be entropy-driven, large changes enthalpy and entropy are observed model system thermolysin. Structural features ultimately determine thermodynamics effect. As service our authors readers, this journal provides supporting information supplied authors. Such materials peer reviewed may re-organized for online delivery, but not copy-edited or...
The discovery of potent, peptide site directed, tyrosine kinase inhibitors has remained an elusive goal. Herein we describe the two such clinical candidates that inhibit Src. Compound 1 is a phase 3 trial candidate likely to provide first in class topical treatment for actinic keratosis (AK) with good efficacy and dramatically less toxicity compared existing standard therapy. 2 malignant glioblastoma induces 30% long-term complete tumor remission animal models. strategy these compounds...
An inhibitor of the insulin receptor tyrosine kinase (IRTK), (hydroxy-2-naphthalenyl-methyl) phosphonic acid, was designed and synthesized shown to be an biological effects in vitro. With a wheat germ purified human placental preparation, this compound inhibited insulin-stimulated autophosphorylation 95-kDa beta-subunit (IC50 = 200 microM). The ability phosphorylate exogenous peptide substrate, angiotensin II, also inhibited. Half-maximal inhibition basal IRTK activity found at...
Accurately predicting the binding affinity of ligands to their receptors by computational methods is one major challenges in structure-based drug design. One potentially significant errors these predictions common assumption that ligand contributions noncovalent interactions are additive. Herein we present data obtained from two separate series thrombin inhibitors containing hydrophobic side chains increasing size bind S3 pocket and with, or without, an adjacent amine engages a hydrogen bond...
Abstract Purpose: To investigate the antitumor effects of targeting Src and tubulin in mucinous ovarian carcinoma. Experimental Design: The vitro vivo molecular mechanisms KX-01, which inhibits pathway polymerization, were examined cancer models. Results: In studies using RMUG-S RMUG-L cell lines showed that KX-01 inhibited proliferation, induced apoptosis, arrested cycle at G2–M phase, enhanced cytotoxicity oxaliplatin KX-01–sensitive line, RMUG-S. significantly decreased tumor burden mouse...
Src kinase is elevated in breast tumors that are ER/PR negative and do not overexpress HER2, but clinical trials with inhibitors have shown little activity. The present study evaluated preclinical efficacy of a novel peptidomimetic compound, KX-01 (KX2-391), exhibits dual action as an pretubulin inhibitor. was single-agent combination paclitaxel MDA-MB-231, MDA-MB-157, MDA-MB-468 human ER/PR/HER2-negative cancer cells. Treatments were by growth/apoptosis, isobologram analysis,...
The design of P2-P3 conformational restrictions in renin inhibitors by the use a computer graphic model led to synthesis containing N-Boc, N-acetyl, and N-phthalyl derivatives 3(S)-amino-4(R,S)-2-piperidones 4(S)-amino-2-benzazepinones place phenylalanine control compound N-acetyl-L-phenylalanyl-N-[4(S)-[(butylamino)carbonyl]-1(S)- (cyclohexylmethyl)-2(S)-hydroxy-5-methylhexyl]-L-norleuci namide (32). piperidone were prepared utilization Evans chiral auxilliary introduce amino group with...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTotal synthesis of pseudoguaianolides: (.+-.)-aromaticin and (.+-.)-aromatinPeter T. Lansbury, David G. Hangauer Jr., Joseph P. VaccaCite this: J. Am. Chem. Soc. 1980, 102, 11, 3964–3965Publication Date (Print):May 1, 1980Publication History Published online1 May 2002Published inissue 1 1980https://pubs.acs.org/doi/10.1021/ja00531a055https://doi.org/10.1021/ja00531a055research-articleACS PublicationsRequest reuse permissionsArticle...
Ligand functional groups can modulate the contributions of one another to ligand-protein binding thermodynamics, producing either positive or negative cooperativity. Data presented for four thermolysin phosphonamidate inhibitors demonstrate that differential free energy and enthalpy caused by replacement a H with Me group, which binds in well-hydrated S2' pocket, are more favorable presence ligand carboxylate. The entropy is however less favorable. Dissection these thermodynamic parameters,...
Purpose KX-01 is a novel dual inhibitor of Src and tubulin. Unlike previous inhibitors that failed to show clinical benefit during treatment breast cancer, can potentially overcome the therapeutic limitations current through inhibition both The present study further evaluates activity mechanism in vitro vivo. Materials Methods antitumor effect triple negative cancer (TNBC) cell lines was determined by MTT assay. Wound healing immunofluorescence assays were performed evaluate action...
Small changes, big effects: Two thrombin inhibitors (see picture; R=cyclopentyl (1 a), R=cyclohexyl b)) were characterized thermodynamically and computationally to explain their identical binding constants. Surprisingly, the free energy of is achieved with different enthalpic entropic contributions plot).