Delving into the Latest Updates on GNF-2133 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

DYRK1A

Mechanism

DYRK1A inhibitors(Dual-specificity tyrosine-phosphorylation regulated kinase 1A inhibitors)

Therapeutic Areas

Immune System DiseasesEndocrinology and Metabolic Disease

Active Indication

Diabetes Mellitus, Type 1

Inactive Indication-

Originator Organization

Genomics Institute Of The Novartis Research Foundation

Active Organization

Genomics Institute Of The Novartis Research Foundation

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC24H30N6O2

InChIKeySAZIAQSVBIWIDU-UHFFFAOYSA-N

CAS Registry2561414-56-8

Author: Wu, Tom Y.-H. ; Kamireddy, Anwesh ; Pan, Jianfeng ; Liu, Bo ; Colman, Karyn ; Espinola, Sheryll ; Bursulaya, Badry ; Glynne, Richard ; McNamara, Peter ; Nguyen-Tran, Vân ; Li, Jing ; Jia, Yong ; Nguyen, Bao ; Zou, Yefen ; Zhang, You-Qing ; Shen, Weijun ; Liu, Yahu A. ; Jin, Qihui ; Ha, Sukwon ; Gordon, W. Perry ; DiDonato, Michael ; Qiu, Minhua ; Laffitte, Bryan ; Loren, Jon ; Ding, Qiang ; Baaten, Janine ; Mo, Tingting ; Wang, Zhicheng ; Meeusen, Shelly ; Deaton, Lisa ; Harb, George ; Hill, Robert ; Pan, Shifeng ; Schumacher, Andrew M. ; Molteni, Valentina ; Hao, Xueshi ; Jacobsen, Kate ; Zhang, Xiaoyue ; Lam, Thanh ; Petrassi, H. Michael ; Yan, Shanshan

Autoimmune deficiency and destruction in either β-cell mass or function can cause insufficient insulin levels and, as a result, hyperglycemia and diabetes. Thus, promoting β-cell proliferation could be one approach toward diabetes intervention. In this report we describe the discovery of a potent and selective DYRK1A inhibitor GNF2133, which was identified through optimization of a 6-azaindole screening hit. In vitro, GNF2133 is able to proliferate both rodent and human β-cells. In vivo, GNF2133 demonstrated significant dose-dependent glucose disposal capacity and insulin secretion in response to glucose-potentiated arginine-induced insulin secretion (GPAIS) challenge in rat insulin promoter and diphtheria toxin A (RIP-DTA) mice. The work described here provides new avenues to disease altering therapeutic interventions in the treatment of type 1 diabetes (T1D).

100 Deals associated with GNF-2133

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