2. Academic Validation
  3. Identification and optimization of pteridinone Toll-like receptor 7 (TLR7) agonists for the oral treatment of viral hepatitis

Identification and optimization of pteridinone Toll-like receptor 7 (TLR7) agonists for the oral treatment of viral hepatitis

  • J Med Chem. 2013 Sep 26;56(18):7324-33. doi: 10.1021/jm400815m.
Paul A Roethle 1,  Ryan M McFadden,  Hong Yang,  Paul Hrvatin,  Hon Hui,  Michael Graupe,  Brian Gallagher,  Jessica Chao,  Joseph Hesselgesser,  Paul Duatschek,  Jim Zheng,  Bing Lu,  Daniel B Tumas,  Jason Perry,  Randall L Halcomb
Affiliations

Affiliation

  • 1 Departments of †Medicinal Chemistry, ‡Clinical Virology, §Drug Metabolism, ∥Biology, and ⊥Structural Chemistry, Gilead Sciences , 333 Lakeside Drive, Foster City, California 94404, United States.
PMID: 23961878 DOI: 10.1021/jm400815m
Abstract

Pteridinone-based Toll-like Receptor 7 (TLR7) agonists were identified as potent and selective alternatives to the previously reported adenine-based agonists, leading to the discovery of GS-9620. Analogues were optimized for the immunomodulatory activity and selectivity versus Other TLRs, based on differential induction of key cytokines including interferon α (IFN-α) and tumor necrosis factor α (TNF-α). In addition, physicochemical properties were adjusted to achieve desirable in vivo pharmacokinetic and pharmacodynamic properties. GS-9620 is currently in clinical evaluation for the treatment of chronic hepatitis B (HBV) Infection.

Figures
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z