The Exploration of Chirality for Improved Druggability within the Human Kinome

Debasmita Saha, Anupreet Kharbanda, Wei Yan, Naga Rajiv Lakkaniga, Brendan Frett, Hong Yu Li

Research output: Contribution to journalReview article

Abstract

Chirality is important in drug discovery because stereoselective drugs can ameliorate therapeutic difficulties including adverse toxicity and poor pharmacokinetic profiles. The human kinome, a major druggable enzyme class has been exploited to treat a wide range of diseases. However, many kinase inhibitors are planar and overlap in chemical space, which leads to selectivity and toxicity issues. By exploring chirality within the kinome, a new iteration of kinase inhibitors is being developed to better utilize the three-dimensional nature of the kinase active site. Exploration into novel chemical space, in turn, will also improve drug solubility and pharmacokinetic profiles. This perspective explores the role of chirality to improve kinome druggability and will serve as a resource for pioneering kinase inhibitor development to address current therapeutic needs. ©

Original languageEnglish (US)
JournalJournal of Medicinal Chemistry
DOIs
StateAccepted/In press - Jan 1 2019
Externally publishedYes

Fingerprint

Phosphotransferases
Pharmacokinetics
Drug Discovery
Pharmaceutical Preparations
Solubility
Catalytic Domain
Enzymes
Therapeutics

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

The Exploration of Chirality for Improved Druggability within the Human Kinome. / Saha, Debasmita; Kharbanda, Anupreet; Yan, Wei; Lakkaniga, Naga Rajiv; Frett, Brendan; Li, Hong Yu.

In: Journal of Medicinal Chemistry, 01.01.2019.

Research output: Contribution to journalReview article

Saha, Debasmita ; Kharbanda, Anupreet ; Yan, Wei ; Lakkaniga, Naga Rajiv ; Frett, Brendan ; Li, Hong Yu. / The Exploration of Chirality for Improved Druggability within the Human Kinome. In: Journal of Medicinal Chemistry. 2019.
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