General
Preferred name
FASIGLIFAM
Synonyms
TAK875 ()
TAK-875 ()
AK875 ()
TAK 875 ()
cpd 9a ()
Fasiglifam hemihydrate ()
TAK-875 Hemihydrate ()
Fasiglifam(TAK-875) Hemihydrate ()
FASIGLIFAM HYDRATE ()
TAK-875 ANHYDROUS ()
P&D ID
PD012943
CAS
1000413-72-8
1374598-80-7
Tags
available
probe
drug candidate
biased GPCR ligand
Drug indication
Type-2 diabetes
diabetes mellitus
Drug Status
investigational
Max Phase
3.0
Probe info
Probe type
P&D approved
experimental probe
Probe selectivity
protein-selective
Probe sources
Chemical Probes.org
High-quality chemical probes
Probe targets
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
DESCRIPTION Fasiglifam is a positive allosteric modulator/partial agonist of the free fatty acid receptor 1 (FFA1, a.k.a. GPR40) . In the presence of endogenous free fatty acids (FFAs) fasiglifam enhances insulin secretion, by binding to an allosteric site distinct from the orthosteric FFA binding site. On its own, it elicits a low level of insulin secretion. These findings indicate that fasiglifam acts cooperatively with FFAs to promote insulin secretion. (GtoPdb)
COMMENT Fasiglifam is an ago-allosteric modulator of  free fatty acid receptor 1 (FFAR1(GPR40)), which amplifies the agonistic activity of the endogenous ligand c-linolenic acid (c-LA) by binding to an allosteric site of FFAR1. Fasiglifam alone exhibited partial agonistic activity in cells expressing moderate levels of FFAR1, and exerted positive cooperative effects with free fatty acids (FFAs) in vitro and in vivo. Fasiglifam displays excellent potency and selectivity for FFAR1 (EC50=14nM) over other members of the FFA receptor family (GPR41, GPR43, GPR120, for which EC50>10 μM). Partial agonistic activity of Fasiglifam as determined by intracellular calcium mobilization assays in CHO cells is dependent upon FFAR1 gene expression levels and augmentation of glucose-induced insulin secretion by fasiglifam, c-LA, or their combination was completely abolished in pancreatic islets of FFAR1-knockout mice (doi:10.1371/journal.pone.0076280) providing additional evidence for selectivity. Fasiglifam advanced into the clinic but was terminated due to idiosyncratic liver toxicity. Mar 29 2021 - 9:27pm; Compound not tested for x-reactivity outside the FAR-family.  The  liver safety aspect has been mechanistically investigated in   https://pubmed.ncbi.nlm.nih.gov/30243991/   and  https://pubmed.ncbi.nlm.nih.gov/28206647/ Primary Takeda patent filing with initial SAR is probably  US20120046338 – Fused cyclic compounds  Apr 10 2021 - 1:13pm
DESCRIPTION Fasiglifam (TAK-875) is a potent, selective and orally bioavailable GPR40 agonist with EC50 of 72 nM.
PRICE 168
MOA Agonist (Chemical Probes.org)
DESCRIPTION Fasiglifam (TAK875) is a potent, selective and orally bioavailable GPR40 agonist. (TargetMol Bioactive Compound Library)
DESCRIPTION TAK-875 is a novel, orally available, selective GPR40 agonist. TAK-875 exhibits potent agonist activity and high binding affinity to the human GPR40 receptor with Ki of 38 nM. TAK-875 enhanced glucose-induced insulin secretion in a glucose-dependent manner in both human and rat islets. In rat insulinoma INS-1 833/15 cells, TAK-875 increased intracellular inositol monophosphate and calcium concentration, consistent with activation of the Gqα signaling pathway. In addition, TAK-875 (10 mg/kg, p.o.) significantly augmented plasma insulin levels and reduced fasting hyperglycemia in male Zucker diabetic fatty rats, whereas in fasted normal Sprague-Dawley rats, TAK-875 neither enhanced insulin secretion nor caused hypoglycemia even at 30 mg/kg. TAK-875 improves both postprandial and fasting hyperglycemia with a low risk of hypoglycemia and no evidence of β cell toxicity. TAK-875 significantly improved glycaemic control in patients with type 2 diabetes with minimum risk of hypoglycaemia. (BOC Sciences Bioactive Compounds)
Cell lines
0
Organisms
1
Compound Sets
24
AdooQ Bioactive Compound Library
A11018
BiasDB
Fasiglifam
BOC Sciences Bioactive Compounds
tak-875-hemihydrate-cas-1374598-80-7-462303
Cayman Chemical Bioactives
17335
ChEMBL Drugs
CHEMBL1829174
Chemical Probes.org
fasiglifam
Concise Guide to Pharmacology 2017/18
6484
Concise Guide to Pharmacology 2019/20
6484
Concise Guide to Pharmacology 2021/22
6484
Concise Guide to Pharmacology 2023/24
6484
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DB12491
DrugMAP
DMIM5AP
DMTGYSO
EU-OPENSCREEN Bioactive Compound Library
EOS101818
EUbOPEN Chemogenomics Library
EUB0000769
Guide to Pharmacology
6484
High-quality chemical probes
PD012943
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL1829174
MedChem Express Bioactive Compound Library
HY-10480
Novartis Chemogenetic Library (NIBR MoA Box)
ReFrame library
Selleckchem Bioactive Compound Library
tak-875
TargetMol Bioactive Compound Library
T2351
External IDs
36
Properties
(calculated by RDKit )
Molecular Weight
524.19
Hydrogen Bond Acceptors
6
Hydrogen Bond Donors
1
Rotatable Bonds
11
Ring Count
4
Aromatic Ring Count
3
cLogP
5.31
TPSA
99.13
Fraction CSP3
0.34
Chiral centers
1.0
Largest ring
6.0
QED
0.34
QED
0.34
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
GPR40
GPR40(FFA1)
FFAR1
GPR
Free Fatty Acid Receptor
Member status
member
MOA
"Free Fatty Acid Receptor 1 (FFAR1
GPR40) Agonists"
insulin secretagogue
Orthogonal probe
TUG-469
Pathway
GPCR/G protein
Endocrinology/Hormones
Target class
GPCR
Target subclass
Free fatty acid receptor
Control
cpd 9b
Recommended Cell Concentration
1 uM
Source data