2. Academic Validation
  3. Discovery of potent and orally bioavailable inhibitors of Human Uric Acid Transporter 1 (hURAT1) and binding mode prediction using homology model

Discovery of potent and orally bioavailable inhibitors of Human Uric Acid Transporter 1 (hURAT1) and binding mode prediction using homology model

  • Bioorg Med Chem Lett. 2016 Jan 15;26(2):277-282. doi: 10.1016/j.bmcl.2015.12.040.
Jianbiao Peng 1,  Qiyue Hu 2,  Chunyan Gu 2,  Bonian Liu 2,  Fangfang Jin 2,  Jijun Yuan 2,  Jun Feng 2,  Lei Zhang 2,  Jiong Lan 2,  Qing Dong 2,  Guoqing Cao 2
Affiliations

Affiliations

  • 1 Shanghai Hengrui Pharmaceutical Co. Ltd, 279 Wenjing Rd., Shanghai 200245, China. Electronic address: pengjb@shhrp.com.
  • 2 Shanghai Hengrui Pharmaceutical Co. Ltd, 279 Wenjing Rd., Shanghai 200245, China.
PMID: 26704267 DOI: 10.1016/j.bmcl.2015.12.040
Abstract

This Letter describes the discovery of a series of potent inhibitors of Human Uric Acid Transporter 1 (hURAT1). Lead generation and optimization via 3D pharmacophore analysis resulted in compound 41. With an IC50 of 33.7nM, 41 also demonstrated good oral bioavailability in rat (74.8%) and displayed a consistent PK profile across all species tested (rat, dog and monkey).

Keywords

3D pharmacophore; Gout; Hyperuricemia; URAT1 homology model; URAT1 inhibitors.

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