2. Academic Validation
  3. Structure-Cytotoxicity Relationships of Analogues of N14-Desacetoxytubulysin H

Structure-Cytotoxicity Relationships of Analogues of N14-Desacetoxytubulysin H

  • J Med Chem. 2016 Dec 8;59(23):10781-10787. doi: 10.1021/acs.jmedchem.6b01023.
Dorin Toader 1 2,  Fengjiang Wang 1,  Lakshmaiah Gingipalli 1,  Melissa Vasbinder 1,  Mark Roth 1,  Shenlan Mao 3,  Michael Block 1,  Jay Harper 3,  Sambaiah Thota 1,  Mei Su 1,  Jianquo Ma 1,  Vahe Bedian 1,  Adeela Kamal 3
Affiliations

Affiliations

  • 1 Oncology iMED, AstraZeneca R&D Boston , 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States.
  • 2 Antibody Discovery and Protein Engineering, MedImmune LLC , 1 MedImmune Way, Gaithersburg, Maryland 20878, United States.
  • 3 Oncology Research, MedImmune LLC , Gaithersburg, Maryland 20878, United States.
PMID: 27809515 DOI: 10.1021/acs.jmedchem.6b01023
Abstract

Herein we report structure-cytotoxicity relationships for analogues of N14-desacetoxytubulyisn H 1. A novel synthetic approach toward 1 enabled the discovery of compounds with a range of activity. Calculated basicity of the N-terminus of tubulysins was shown to be a good predictor of cytotoxicity. The impact of structural modifications at the C-terminus of 1 upon cytotoxicity is also described. These findings will facilitate the development of new tubulysin analogues for the treatment of Cancer.

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