Delving into the Latest Updates on AM-3189 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

GPR40

Action

agonists

Mechanism

GPR40 agonists(Free fatty acid receptor 1 agonists)

Therapeutic Areas

Endocrinology and Metabolic Disease

Active Indication-

Inactive Indication

Diabetes Mellitus, Type 2

Originator Organization

Amgen, Inc.

Active Organization-

Inactive Organization

Amgen, Inc.

License Organization-

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC27H25ClN2O3

InChIKeyGFFXCPIMXLSUGF-VWLOTQADSA-N

CAS Registry916219-50-6

As a follow-up to the GPR40 agonist AMG 837, which was evaluated in clinical trials for the treatment of type II diabetes, further optimization led to the discovery of AM-3189 (13k). AM-3189 is representative of a new class of compounds with minimal CNS penetration, superior pharmacokinetic properties and in vivo efficacy comparable to AMG 837.

08 May 2014·ACS medicinal chemistry lettersQ3 · MEDICINE

Optimization of GPR40 Agonists for Type 2 Diabetes

Q3 · MEDICINE

Article

Author: Lin, Daniel C.-H. ; Houze, Jonathan B. ; Medina, Julio C. ; Brown, Sean P. ; Dransfield, Paul J. ; Zhu, Liusheng ; Zhang, Jane ; Swaminath, Gayathri ; Luo, Jian ; Sharma, Rajiv ; Schmitt, Mike ; Sun, Ying ; Ma, Zhihua ; Tonn, George R. ; Wang, Yingcai ; Zhuang, Run ; Guo, Qi ; Liu, Jiwen (Jim) ; Wong, Simon

GPR40 (FFA1 and FFAR1) has gained significant interest as a target for the treatment of type 2 diabetes. TAK-875 (1), a GPR40 agonist, lowered hemoglobin A1c (HbA1c) and lowered both postprandial and fasting blood glucose levels in type 2 diabetic patients in phase II clinical trials. We optimized phenylpropanoic acid derivatives as GPR40 agonists and identified AMG 837 (2) as a clinical candidate. Here we report our efforts in searching for structurally distinct back-ups for AMG 837. These efforts led to the identification of more polar GPR40 agonists, such as AM-4668 (10), that have improved potency, excellent pharmacokinetic properties across species, and minimum central nervous system (CNS) penetration.

100 Deals associated with AM-3189

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