Metaglidasen

Metaglidasen
Clinical data
Other names	MBX‑102
Identifiers
	IUPAC name 2-(4-chlorophenyl)-2-[3-(trifluoromethyl)phenoxy]acetic acid;
CAS Number	4687-08-5;
PubChem CID	9949411;
ChemSpider	8125022;
UNII	V02QWF9PMI;
ChEMBL	ChEMBL451321;
PDB ligand	MGZ (PDBe, RCSB PDB);
Chemical and physical data
Formula	C15H10ClF3O3
Molar mass	330.69 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C1=CC(=CC(=C1)OC(C2=CC=C(C=C2)Cl)C(=O)O)C(F)(F)F;
	InChI InChI=InChI=1S/C15H10ClF3O3/c16-11-6-4-9(5-7-11)13(14(20)21)22-12-3-1-2-10(8-12)15(17,18)19/h1-8,13H,(H,20,21); Key:DDTQLPXXNHLBAB-UHFFFAOYSA-N;

Metaglidasen was a fibrate-like drug candidate developed by Metabolex, Inc. that acts as a selective receptor modulator of the peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear receptor involved in regulating genes linked to glucose and lipid metabolism.

In contrast to traditional thiazolidinedione antidiabetic agents, metaglidasen was claimed to lower plasma glucose levels without common side effects such as weight gain and edema.^[1]^[2]

Pharmacology

It is a racemic mixture of two stereoisomers with distinct activities on PPAR subtypes: both show partial agonist activity on PPARγ, while their effects on PPARα differ, with one enantiomer acting as a partial agonist and the other as an antagonist.^[1] Additionally, metaglidasen’s metabolically active form has been studied for its impact on skeletal muscle chloride channels, revealing a potentially more favorable safety profile compared to other fibrates.^[1] Even though the drug made it into phase II/III clinical trials, it was never approved as an anti-diabetic agent.^[3]

References

1 2 3 Laghezza A, Montanari R, Lavecchia A, Piemontese L, Pochetti G, Iacobazzi V, et al. (March 2015). "On the metabolically active form of metaglidasen: improved synthesis and investigation of its peculiar activity on peroxisome proliferator-activated receptors and skeletal muscles". ChemMedChem. 10 (3): 555–65. doi:10.1002/cmdc.201402462. hdl:11586/140990. PMID 25641779.
↑ Chang F, Jaber LA, Berlie HD, O'Connell MB (June 2007). "Evolution of peroxisome proliferator-activated receptor agonists". The Annals of Pharmacotherapy. 41 (6): 973–83. doi:10.1345/aph.1K013. PMID 17519293.
↑ Zhang F, Lavan BE, Gregoire FM (2007). "Selective Modulators of PPAR-gamma Activity: Molecular Aspects Related to Obesity and Side-Effects". PPAR Research. 2007 32696. doi:10.1155/2007/32696. PMC 1783742. PMID 17389769.

[Laghezza_2015-1] 1 2 3 Laghezza A, Montanari R, Lavecchia A, Piemontese L, Pochetti G, Iacobazzi V, et al. (March 2015). "On the metabolically active form of metaglidasen: improved synthesis and investigation of its peculiar activity on peroxisome proliferator-activated receptors and skeletal muscles". ChemMedChem. 10 (3): 555–65. doi:10.1002/cmdc.201402462. hdl:11586/140990. PMID 25641779.

[Chang_2007-2] Chang F, Jaber LA, Berlie HD, O'Connell MB (June 2007). "Evolution of peroxisome proliferator-activated receptor agonists". The Annals of Pharmacotherapy. 41 (6): 973–83. doi:10.1345/aph.1K013. PMID 17519293.

[Zhang-3] Zhang F, Lavan BE, Gregoire FM (2007). "Selective Modulators of PPAR-gamma Activity: Molecular Aspects Related to Obesity and Side-Effects". PPAR Research. 2007 32696. doi:10.1155/2007/32696. PMC 1783742. PMID 17389769.

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