X-ray crystallography of Epacadostat in adduct with Carbonic Anhydrase IX

Andrea Angeli; Thomas S. Peat; Silvia Selleri; Abdulmalik Saleh Alfawaz Altamimi; Claudiu T. Supuran; Fabrizio Carta

doi:10.1016/j.bioorg.2020.103669

X-ray crystallography of Epacadostat in adduct with Carbonic Anhydrase IX

Andrea Angeli
, Thomas S. Peat
, Silvia Selleri
, Abdulmalik Saleh Alfawaz Altamimi
, Claudiu T. Supuran
, Fabrizio Carta

Pharmaceutical Chemistry

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

Epacadostat (EPA), a new and promising anti-cancer small molecule is firmly established as selective inhibitor of the enzyme indoleamine 2,3-dioxygenase 1 (IDO1). The X-Ray structure of the human CA IX mimic in complex with EPA is investigated here for the first time and compared to previously reported EPA-CA II adduct. The structural information obtained are all in agreement with the in vitro kinetic data which accounted for a selective inhibition of the CA IX over the CA II isoform.

Original language	English
Article number	103669
Journal	Bioorganic Chemistry
Volume	97
DOIs	https://doi.org/10.1016/j.bioorg.2020.103669
State	Published - Apr 2020

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Carbonic Anhydrase inhibitor
Carbonic Anhydrases IX
Check point inhibitor
Epacadostat
Metalloenzymes

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10.1016/j.bioorg.2020.103669

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title = "X-ray crystallography of Epacadostat in adduct with Carbonic Anhydrase IX",

abstract = "Epacadostat (EPA), a new and promising anti-cancer small molecule is firmly established as selective inhibitor of the enzyme indoleamine 2,3-dioxygenase 1 (IDO1). The X-Ray structure of the human CA IX mimic in complex with EPA is investigated here for the first time and compared to previously reported EPA-CA II adduct. The structural information obtained are all in agreement with the in vitro kinetic data which accounted for a selective inhibition of the CA IX over the CA II isoform.",

keywords = "Carbonic Anhydrase inhibitor, Carbonic Anhydrases IX, Check point inhibitor, Epacadostat, Metalloenzymes",

author = "Andrea Angeli and Peat, \{Thomas S.\} and Silvia Selleri and \{Saleh Alfawaz Altamimi\}, Abdulmalik and Supuran, \{Claudiu T.\} and Fabrizio Carta",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2020",

month = apr,

doi = "10.1016/j.bioorg.2020.103669",

language = "English",

volume = "97",

journal = "Bioorganic Chemistry",

issn = "0045-2068",

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T1 - X-ray crystallography of Epacadostat in adduct with Carbonic Anhydrase IX

AU - Angeli, Andrea

AU - Peat, Thomas S.

AU - Selleri, Silvia

AU - Saleh Alfawaz Altamimi, Abdulmalik

AU - Supuran, Claudiu T.

AU - Carta, Fabrizio

PY - 2020/4

Y1 - 2020/4

N2 - Epacadostat (EPA), a new and promising anti-cancer small molecule is firmly established as selective inhibitor of the enzyme indoleamine 2,3-dioxygenase 1 (IDO1). The X-Ray structure of the human CA IX mimic in complex with EPA is investigated here for the first time and compared to previously reported EPA-CA II adduct. The structural information obtained are all in agreement with the in vitro kinetic data which accounted for a selective inhibition of the CA IX over the CA II isoform.

AB - Epacadostat (EPA), a new and promising anti-cancer small molecule is firmly established as selective inhibitor of the enzyme indoleamine 2,3-dioxygenase 1 (IDO1). The X-Ray structure of the human CA IX mimic in complex with EPA is investigated here for the first time and compared to previously reported EPA-CA II adduct. The structural information obtained are all in agreement with the in vitro kinetic data which accounted for a selective inhibition of the CA IX over the CA II isoform.

KW - Carbonic Anhydrase inhibitor

KW - Carbonic Anhydrases IX

KW - Check point inhibitor

KW - Epacadostat

KW - Metalloenzymes

UR - https://www.scopus.com/pages/publications/85079898914

U2 - 10.1016/j.bioorg.2020.103669

DO - 10.1016/j.bioorg.2020.103669

M3 - Article

C2 - 32088421

AN - SCOPUS:85079898914

SN - 0045-2068

VL - 97

JO - Bioorganic Chemistry

JF - Bioorganic Chemistry

M1 - 103669

ER -

X-ray crystallography of Epacadostat in adduct with Carbonic Anhydrase IX

Abstract

UN SDGs

Keywords

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