2. Academic Validation
  3. Collaborative virtual screening to elaborate an imidazo[1,2- a]pyridine hit series for visceral leishmaniasis

Collaborative virtual screening to elaborate an imidazo[1,2- a]pyridine hit series for visceral leishmaniasis

  • RSC Med Chem. 2021 Jan 21;12(3):384-393. doi: 10.1039/d0md00353k.
Yuichiro Akao 1,  Stacie Canan 2,  Yafeng Cao 3,  Kevin Condroski 2,  Ola Engkvist 4,  Sachiko Itono 1,  Rina Kaki 5,  Chiaki Kimura 5,  Thierry Kogej 4,  Kazuya Nagaoka 6,  Akira Naito 5,  Hiromi Nakai 5,  Garry Pairaudeau 7,  Constantin Radu 8,  Ieuan Roberts 7,  Mitsuyuki Shimada 1,  David Shum 8,  Nao-Aki Watanabe 6,  Huanxu Xie 3,  Shuji Yonezawa 5,  Osamu Yoshida 5,  Ryu Yoshida 5,  Charles Mowbray 9,  Benjamin Perry 9
Affiliations

Affiliations

  • 1 Takeda Pharmaceutical Company Limited 26-1 Muraoka-Higashi 2-chrome Fujisawa Kanagawa 251-8555 Japan.
  • 2 Celgene Corporation, Celgene Global Health 10300 Campus Point Drive San Diego California 92121 USA.
  • 3 WuXi AppTec Company Ltd. 666 Gaoxin Road, East Lake High-Tech Development Zone Wuhan 430075 People's Republic of China.
  • 4 AstraZeneca Discovery Sciences, R&D AstraZeneca Gothenburg Sweden.
  • 5 Shionogi & Co., Ltd 3-1-1, Futaba-cho Toyonaka-shi Osaka Japan.
  • 6 Eisai Co., Ltd 1-3,Tokodai 5-chome Tsukuba Ibaraki 300-2635 Japan.
  • 7 AstraZeneca, Discovery Sciences, R&D AstraZeneca Cambridge UK.
  • 8 Institut Pasteur Korea 16, Daewangpangyo-ro 712 beon-gil, Bundang-gu Seongnam-si Gyeonggi-do 13488 Republic of Korea.
  • 9 Drugs for Neglected Diseases initiative 15 Chemin Louis Dunant Geneva 1202 Switzerland [email protected].
PMID: 34041487 DOI: 10.1039/d0md00353k
Abstract

An innovative pre-competitive virtual screening collaboration was engaged to validate and subsequently explore an imidazo[1,2-a]pyridine screening hit for visceral leishmaniasis. In silico probing of five proprietary pharmaceutical company libraries enabled rapid expansion of the hit chemotype, alleviating initial concerns about the core chemical structure while simultaneously improving antiparasitic activity and selectivity index relative to the background cell line. Subsequent hit optimization informed by the structure-activity relationship enabled by this virtual screening allowed thorough investigation of the pharmacophore, opening avenues for further improvement and optimization of the chemical series.

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