tubulysin-u and Neoplasms

tubulysin-u has been researched along with Neoplasms* in 2 studies

Other Studies

2 other study(ies) available for tubulysin-u and Neoplasms

Article	Year
Improved Total Synthesis of Tubulysins and Design, Synthesis, and Biological Evaluation of New Tubulysins with Highly Potent Cytotoxicities against Cancer Cells as Potential Payloads for Antibody-Drug Conjugates. Journal of the American Chemical Society, 2018, 03-14, Volume: 140, Issue:10 Improved, streamlined total syntheses of natural tubulysins such as V (Tb45) and U (Tb46) and pretubulysin D (PTb-D43), and their application to the synthesis of designed tubulysin analogues (Tb44, PTb-D42, PTb-D47-PTb-D49, and Tb50-Tb120), are described. Cytotoxicity evaluation of the synthesized compounds against certain cancer cell lines revealed a number of novel analogues with exceptional potencies [e.g., Tb111: IC Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Drug Resistance, Multiple; Drug Resistance, Neoplasm; HEK293 Cells; Humans; Immunoconjugates; Neoplasms; Oligopeptides; Pipecolic Acids	2018
Synthesis and structure-activity relationship studies of novel tubulysin U analogues--effect on cytotoxicity of structural variations in the tubuvaline fragment. Organic & biomolecular chemistry, 2013, Apr-14, Volume: 11, Issue:14 Tubulysins are cytotoxic natural products with promising anti-cancer properties, originally isolated from myxobacterial cultures. Structurally, tubulysins are tetrapeptides, incorporating three unusual (Mep, Tuv and Tup) and one proteinogenic amino acid (Ile). Here we describe the synthesis and structure-activity relationship studies of novel tubulysin U and V analogues, with variations in the central Tuv fragment, which is known to be of paramount importance for tubulysins' potency and hence cytotoxicity, but has seldom been modified in previous studies. Specifically, we replaced the natural iso-propyl and acetoxy functionalities with other structurally related groups. In general, the new analogues showed much lower potency relative to native tubulysin U. However, one of the synthetic analogues (1f) having a MOM function replacing the acetyl group exhibited a 22 nM IC50 on the HT-29 cell line which is comparable to the IC(50) displayed by tubulysin U (3.8 nM). Furthermore, the synthetic methodology reported herein was found to be flexible enough to deliver different core-modified tubulysin analogues and hence may be regarded as a scalable and convenient strategy for the chemical generation of novel tubulysin analogues. Topics: Cell Line, Tumor; Crystallography, X-Ray; Genetic Variation; HT29 Cells; Humans; Inhibitory Concentration 50; Molecular Structure; Neoplasms; Oligopeptides; Peptide Fragments; Pipecolic Acids; Structure-Activity Relationship	2013

Article

Year

Improved Total Synthesis of Tubulysins and Design, Synthesis, and Biological Evaluation of New Tubulysins with Highly Potent Cytotoxicities against Cancer Cells as Potential Payloads for Antibody-Drug Conjugates.

Journal of the American Chemical Society, 2018, 03-14, Volume: 140, Issue:10

Improved, streamlined total syntheses of natural tubulysins such as V (Tb45) and U (Tb46) and pretubulysin D (PTb-D43), and their application to the synthesis of designed tubulysin analogues (Tb44, PTb-D42, PTb-D47-PTb-D49, and Tb50-Tb120), are described. Cytotoxicity evaluation of the synthesized compounds against certain cancer cell lines revealed a number of novel analogues with exceptional potencies [e.g., Tb111: IC

Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Drug Resistance, Multiple; Drug Resistance, Neoplasm; HEK293 Cells; Humans; Immunoconjugates; Neoplasms; Oligopeptides; Pipecolic Acids

2018

Synthesis and structure-activity relationship studies of novel tubulysin U analogues--effect on cytotoxicity of structural variations in the tubuvaline fragment.

Organic & biomolecular chemistry, 2013, Apr-14, Volume: 11, Issue:14

Tubulysins are cytotoxic natural products with promising anti-cancer properties, originally isolated from myxobacterial cultures. Structurally, tubulysins are tetrapeptides, incorporating three unusual (Mep, Tuv and Tup) and one proteinogenic amino acid (Ile). Here we describe the synthesis and structure-activity relationship studies of novel tubulysin U and V analogues, with variations in the central Tuv fragment, which is known to be of paramount importance for tubulysins' potency and hence cytotoxicity, but has seldom been modified in previous studies. Specifically, we replaced the natural iso-propyl and acetoxy functionalities with other structurally related groups. In general, the new analogues showed much lower potency relative to native tubulysin U. However, one of the synthetic analogues (1f) having a MOM function replacing the acetyl group exhibited a 22 nM IC50 on the HT-29 cell line which is comparable to the IC(50) displayed by tubulysin U (3.8 nM). Furthermore, the synthetic methodology reported herein was found to be flexible enough to deliver different core-modified tubulysin analogues and hence may be regarded as a scalable and convenient strategy for the chemical generation of novel tubulysin analogues.

Topics: Cell Line, Tumor; Crystallography, X-Ray; Genetic Variation; HT29 Cells; Humans; Inhibitory Concentration 50; Molecular Structure; Neoplasms; Oligopeptides; Peptide Fragments; Pipecolic Acids; Structure-Activity Relationship

2013