Fasiglifam

Summary

Fasiglifam (CHEMBL1829174) is a phase-3 clinical-stage small molecule targeting FFAR1; indicated across 2 conditions including diabetes mellitus and type 2 diabetes mellitus.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (FFAR1)
• Indications: 2 conditions
• Clinical trials: 18
• Chemistry: 524.6 Da · C29H32O7S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1829174
Name	Fasiglifam
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	24857286
Molecular formula	C29H32O7S
Molecular weight	524.6
InChIKey	BZCALJIHZVNMGJ-HSZRJFAPSA-N

SMILES: CC1=CC(=CC(=C1C2=CC=CC(=C2)COC3=CC4=C(C=C3)[C@@H](CO4)CC(=O)O)C)OCCCS(=O)(=O)C

IUPAC name: 2-[(3S)-6-[[3-[2,6-dimethyl-4-(3-methylsulfonylpropoxy)phenyl]phenyl]methoxy]-2,3-dihydro-1-benzofuran-3-yl]acetic acid

Also known as: Fasiglifam, Fasiglifam hemihydrate, Fasiglifam hydrate, TAK-875, Tak-875 anhydrous, TAK875, FASIGLIFAM, AK875, TAK 875, CPD 9A, FASIGLIFAM HYDRATE, TAK-875 ANHYDROUS

Parent form; salt/anhydrous children: CHEMBL2047159, CHEMBL2047171

Patent coverage: 275 distinct patent families (815 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 623 (76%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
FFAR1	FFA1 receptor	Agonist	7.1	0.4%	O14842

Broader ChEMBL bioactivity targets: 8 (assay-derived). Sample: Solute carrier organic anion transporter family member 1B1, Solute carrier organic anion transporter family member 1B3, Free fatty acid receptor 1, Free fatty acid receptor 1, Hepatic sodium/bile acid cotransporter, Free fatty acid receptor 1, GPR40-Galpha16, ATP-binding cassette sub-family C member 2.

Bioactivity

ChEMBL activities: 48 potent at pChembl ≥ 5 of 50 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
FFAR1	9.46	EC50	0.35	nM	CHEMBL_ACT_22951012
FFAR1	8.72	EC50	1.9	nM	CHEMBL_ACT_16781742
FFAR1	8.35	Kd	4.5	nM	CHEMBL_ACT_22951074
FFAR1	8.11	Ki	7.7	nM	CHEMBL_ACT_22950724
FFAR1	8.11	EC50	7.7	nM	CHEMBL_ACT_25024977
Q76JU9	8.07	EC50	8.6	nM	CHEMBL_ACT_22950884
FFAR1	8.03	EC50	9.33	nM	CHEMBL_ACT_16622113
FFAR1	7.92	Kd	11.9	nM	CHEMBL_ACT_22893559
FFAR1	7.92	EC50	12	nM	CHEMBL_ACT_22950820
FFAR1	7.85	EC50	14	nM	CHEMBL_ACT_18374541
FFAR1	7.85	EC50	14	nM	CHEMBL_ACT_18776800
FFAR1	7.85	EC50	14	nM	CHEMBL_ACT_25704603
FFAR1	7.85	EC50	14.13	nM	CHEMBL_ACT_6366467
FFAR1	7.8	EC50	16	nM	CHEMBL_ACT_10938309
FFAR1	7.72	EC50	19	nM	CHEMBL_ACT_25920737
FFAR1	7.64	EC50	23	nM	CHEMBL_ACT_29312116
FFAR1	7.57	EC50	27	nM	CHEMBL_ACT_18046153
FFAR1	7.56	EC50	27.5	nM	CHEMBL_ACT_16570029
FFAR1	7.54	Ki	28.84	nM	CHEMBL_ACT_16622124
FFAR1	7.53	EC50	29.6	nM	CHEMBL_ACT_15726123
FFAR1	7.53	EC50	29.6	nM	CHEMBL_ACT_15751009
FFAR1	7.53	EC50	29.6	nM	CHEMBL_ACT_16509836
FFAR1	7.53	EC50	29.5	nM	CHEMBL_ACT_25565122
FFAR1	7.51	EC50	31	nM	CHEMBL_ACT_19172823
FFAR1	7.5	EC50	31.8	nM	CHEMBL_ACT_18569117
FFAR1	7.49	EC50	32.5	nM	CHEMBL_ACT_18674966
FFAR1	7.47	EC50	33.6	nM	CHEMBL_ACT_18463911
FFAR1	7.45	EC50	35.8	nM	CHEMBL_ACT_25565179
Q8K3T4	7.44	EC50	36	nM	CHEMBL_ACT_22950948
FFAR1	7.43	EC50	37.1	nM	CHEMBL_ACT_19050004

Target pathways

Aggregated over 1 target gene(s): FFAR1.

Top Reactome pathways

5 total, by targets touching each:

Pathway	Targets	Genes
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)	1	FFAR1
Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)	1	FFAR1
G alpha (q) signalling events	1	FFAR1
Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion	1	FFAR1
Free fatty acid receptors	1	FFAR1

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
positive regulation of cytosolic calcium ion concentration	1
insulin secretion	1
positive regulation of insulin secretion	1
negative regulation of interleukin-1 beta production	1
glucose homeostasis	1
positive regulation of calcium ion transport	1
response to fatty acid	1
ligand-gated ion channel signaling pathway	1
signal transduction	1

Indications & clinical

Indications

2 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
diabetes mellitus	3	MONDO:0005015	EFO:0000400
type 2 diabetes mellitus	3	MONDO:0005148	MONDO:0005148

Clinical trials

Total trials: 18.

Phase distribution

Phase	Trials
PHASE3	13
PHASE2	3
PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01433393	PHASE3	COMPLETED	Double-blind Comparative Study of TAK-875
NCT01433406	PHASE3	COMPLETED	Long-term Study of TAK-875
NCT01433419	PHASE3	COMPLETED	Open-label Study of TAK-875
NCT01456195	PHASE3	COMPLETED	Comparison of TAK-875 (Fasiglifam) With Placebo in Participants With Type 2 Diabetes
NCT01481116	PHASE3	TERMINATED	Efficacy and Safety of TAK-875 Compared to Glimepiride When Used With Metformin in Participants With Type 2 Diabetes
NCT01549964	PHASE3	TERMINATED	Comparison of Fasiglifam (TAK-875) to Placebo and Sitagliptin in Combination With Metformin in Participants With Type 2 Diabetes
NCT01585792	PHASE3	COMPLETED	Double Blind Comparative Study of TAK-875
NCT01609582	PHASE3	TERMINATED	Study of TAK-875 in Adults With Type 2 Diabetes and Cardiovascular Disease or Risk Factors for Cardiovascular Disease
NCT01647542	PHASE3	TERMINATED	Study to Evaluate the Efficacy and Safety of Daily Oral TAK-875 25 and 50mg in Asia Pacific Adults With Type 2 Diabetes
NCT01829464	PHASE3	TERMINATED	TAK-875 (Fasiglifam) in Combination With Sitagliptin in Adults With Type 2 Diabetes
NCT01829477	PHASE3	TERMINATED	Comparison of TAK-875 to Placebo as an Add-on to Glimepiride in Patients With Type 2 Diabetes
NCT01834274	PHASE3	TERMINATED	Comparison of Fasiglifam (TAK-875) With Sitagliptin When Used in Combination With Metformin in Patients With Type 2 Diabetes
NCT02015780	PHASE3	WITHDRAWN	Fasiglifam in Type 2 Diabetic Subjects With Chronic Kidney Disease Stage 4 or 5 on Hemodialysis
NCT01007097	PHASE2	COMPLETED	Efficacy and Safety of TAK-875 in Subjects With Type 2 Diabetes Mellitus
NCT01414920	PHASE2	COMPLETED	Efficacy and Safety of TAK-875 in Combination With Sitagliptin in Participants With Type 2 Diabetes Mellitus
NCT01982253	PHASE2	TERMINATED	Fasiglifam 25 mg BID vs 50 mg QD
NCT00949091	PHASE1	COMPLETED	Pharmacokinetics and Pharmacodynamics of TAK-875 in Subjects With Type 2 Diabetes
NCT01496443	PHASE1	COMPLETED	TAK-875 Glimepiride Drug-Interaction Study

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

5 molecules share ≥1 primary target. Top 5 by shared-target count:

Molecule	Source	Status	Shared targets
ROSIGLITAZONE	ChEMBL	Phase 4 (approved)	FFAR1
DOCONEXENT	ChEMBL	Phase 3	FFAR1
GAMOLENIC ACID	ChEMBL	Phase 3	FFAR1
FENBUFEN	ChEMBL	Phase 2	FFAR1
LINOLEIC ACID	ChEMBL	Phase 2	FFAR1