Discovery of Lanraplenib (GS-9876): A Once-Daily Spleen Tyrosine Kinase Inhibitor for Autoimmune Diseases

被引：31

作者：

Blomgren, Peter ^{[1
]}

Chandrasekhar, Jayaraman ^{[1
]}

Di Paolo, Julie A. ^{[2
]}

Fung, Wanchi ^{[2
]}

Geng, Guoju ^{[2
]}

Ip, Carmen ^{[2
]}

Jones, Randall ^{[1
]}

Kropf, Jeffrey E. ^{[1
]}

Lansdon, Eric B. ^{[2
]}

Lee, Seung ^{[1
]}

Lo, Jennifer R. ^{[1
]}

Mitchell, Scott A. ^{[1
]}

Murray, Bernard ^{[2
]}

Pohlmeyer, Chris ^{[2
]}

Schmitt, Aaron ^{[1
]}

Suekawa-Pirrone, Kimberly ^{[2
]}

Wise, Sarah ^{[2
]}

Xiong, Jin-Ming ^{[1
,2
]}

Xu, Jianjun ^{[1
,2
]}

Yu, Helen ^{[2
]}

Zhao, Zhongdong ^{[1
,2
]}

Currie, Kevin S. ^{[1
]}

机构：

[1] Gilead Sci, Seattle, WA 98102 USA

[2] Gilead Sci, Foster City, CA 94404 USA

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2020年 / 11卷 / 04期

关键词：

SYK; kinase inhibitor; solubility; lupus; SYK; ENTOSPLETINIB; GS-9973; POTENT;

D O I：

10.1021/acsmedchemlett.9b00621

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Spleen tyrosine kinase (SYK) is a critical regulator of signaling in a variety of immune cell types such as B-cells, monocytes, and macrophages. Accordingly, there have been numerous efforts to identify compounds that selectively inhibit SYK as a means to treat autoimmune and inflammatory diseases. We previously disclosed GS-9973 (entospletinib) as a selective SYK inhibitor that is under clinical evaluation in hematological malignancies. However, a BID dosing regimen and drug interaction with proton pump inhibitors (PPI) prevented development of entospletinib in inflammatory diseases. Herein, we report the discovery of a second-generation SYK inhibitor, GS-9876 (lanraplenib), which has human pharmacokinetic properties suitable for once-daily administration and is devoid of any interactions with PPI. Lanraplenib is currently under clinical evaluation in multiple autoimmune indications.

引用

页码：506 / 513

页数：8

共 50 条

[31] A Phase 1 dose-escalation study of the safety and pharmacokinetics of once-daily oral foretinib, a multi-kinase inhibitor, in patients with solid tumors
Geoffrey I. Shapiro
Stewart McCallum
Laurel M. Adams
Laurie Sherman
Steve Weller
Suzanne Swann
Harold Keer
Dale Miles
Thomas Müller
Patricia LoRusso
Investigational New Drugs, 2013, 31 : 742 - 750
[32] A Phase 1 dose-escalation study of the safety and pharmacokinetics of once-daily oral foretinib, a multi-kinase inhibitor, in patients with solid tumors
Shapiro, Geoffrey I.
McCallum, Stewart
Adams, Laurel M.
Sherman, Laurie
Weller, Steve
Swann, Suzanne
Keer, Harold
Miles, Dale
Mueller, Thomas
LoRusso, Patricia
INVESTIGATIONAL NEW DRUGS, 2013, 31 (03) : 742 - 750
[33] JTE-852, a novel spleen tyrosine kinase inhibitor, blocks immunoglobulin G-mediated cellular responses and autoimmune reactions in vivo
Kato, Toshinobu
Ohta, Takeshi
Iwasaki, Hidenori
Kobayashi, Hatsue
Matsuo, Akira
Hata, Takahiro
Matsushita, Mutsuyoshi
LIFE SCIENCES, 2017, 191 : 166 - 174
[34] The Spleen Tyrosine Kinase Inhibitor, Entospletinib (GS-9973) Restores Chemosensitivity in Lung Cancer Cells by Modulating ABCG2-mediated Multidrug Resistance
Narayanan, Silpa
Wu, Zhuo-Xun
Wang, Jing-Quan
Ma, Hansu
Acharekar, Nikita
Koya, Jagadish
Yoganathan, Sabesan
Fang, Shuo
Chen, Zhe-Sheng
Pan, Yihang
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES, 2021, 17 (10): : 2652 - 2665
[35] Discovery of Evobrutinib: An Oral, Potent, and Highly Selective, Covalent Bruton's Tyrosine Kinase (BTK) Inhibitor for the Treatment of Immunological Diseases
Caldwell, Richard D.
Qiu, Hui
Askew, Ben C.
Bender, Andrew T.
Brugger, Nadia
Camps, Montserrat
Dhanabal, Mohanraj
Dutt, Vikram
Eichhorn, Thomas
Gardberg, Anna S.
Goutopoulos, Andreas
Grenningloh, Roland
Head, Jared
Healey, Brian
Hodous, Brian L.
Huck, Bayard R.
Johnson, Theresa L.
Jones, Christopher
Jones, Reinaldo C.
Mochalkin, Igor
Morandi, Federica
Ngan Nguyen
Meyring, Michael
Potnick, Justin R.
Santos, Dusica Cvetinovic
Schmidt, Ralf
Sherer, Brian
Shutes, Adam
Urbahns, Klaus
Follis, Ariele Viacava
Wegener, Ansgar A.
Zimmerli, Simone C.
Liu-Bujalski, Lesley
JOURNAL OF MEDICINAL CHEMISTRY, 2019, 62 (17) : 7643 - 7655
[36] Erratum to: A Phase 1 dose-escalation study of the safety and pharmacokinetics of once-daily oral foretinib, a multi-kinase inhibitor, in patients with solid tumors
Geoffrey I. Shapiro
Stewart McCallum
Laurel M. Adams
Laurie Sherman
Steve Weller
Suzanne Swann
Harold Keer
Dale Miles
Thomas Müller
Daniel C. Rabe
Fabiola Cecchi
Donald P. Bottaro
Patricia LoRusso
Investigational New Drugs, 2015, 33 : 1292 - 1292
[37] HEALTHY VOLUNTEER FIRST-IN-HUMAN EVALUATION OF GS-5816, A NOVEL SECOND GENERATION BROAD-GENOTYPIC NS5A INHIBITOR WITH POTENTIAL FOR ONCE-DAILY DOSING
German, P.
Pang, P.
Yang, C.
Han, L.
Link, J. O.
Kearney, B. P.
Mathias, A.
JOURNAL OF HEPATOLOGY, 2013, 58 : S486 - S486
[38] TAS05567, a Novel Potent and Selective Spleen Tyrosine Kinase Inhibitor, Abrogates Immunoglobulin-Mediated Autoimmune and Allergic Reactions in Rodent Models
Hayashi, Hiroaki
Kaneko, Ryusuke
Demizu, Shunsuke
Akasaka, Daichi
Tayama, Manabu
Harada, Takafumi
Irie, Hiroki
Ogino, Yoshio
Fujino, Naoko
Sasaki, Eiji
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2018, 366 (01): : 84 - 95
[39] Upadacitinib tartrate Tyrosine-protein kinase JAK1 inhibitor Treatment of autoimmune inflammatory diseases Treatment of rheumatoid arthritis
Gajdosik, Z.
DRUGS OF THE FUTURE, 2018, 43 (10) : 731 - 743
[40] A new treatment for autoimmune blistering diseases - the efficacy of the Bruton's tyrosine kinase inhibitor PRN473 in canine pemphigus foliaceus
Outerbridge, Catherine
White, Stephen
Varjonen, Katarina
Goodale, Elizabeth
Borjesson, Dori
Murrell, Dedee
Bisconte, Angelina
Hill, Ronald
Masjedizadeh, Mohammad
Gourlay, Steven
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 2016, 74 (05) : AB141 - AB141

← 1 2 3 4 5 →