Tesaglitazar

Tesaglitazar (also known as AZ 242) is a dual peroxisome proliferator-activated receptor agonist with affinity to PPARα and PPARγ, proposed for the management of type 2 diabetes.[1]

Tesaglitazar
Clinical data

ATC code	None
Legal status
Legal status	Development terminated
Identifiers
IUPAC name (2S)-2-Ethoxy-3-[4-[2-(4-methylsulfonyloxyphenyl) ethoxy]phenyl]propanoic acid
CAS Number	251565-85-2^Y
PubChem CID	208901
ChemSpider	180999^N
UNII	6734037O3L
KEGG	D01274^Y
ChEMBL	ChEMBL521632^N
CompTox Dashboard (EPA)	DTXSID4048773
ECHA InfoCard	100.201.079
Chemical and physical data
Formula	C₂₀H₂₄O₆S
Molar mass	392.47 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CCO[C@@H](CC1=CC=C(C=C1)OCCC2=CC=C(C=C2)OS(=O)(=O)C)C(=O)O
InChI InChI=1S/C20H24O6S/c1-3-25-19(20(21)22)14-16-6-8-17(9-7-16)26-13-12-15-4-10-18(11-5-15)27-28(2,23)24/h4-11,19H,3,12-14H2,1-2H3,(H,21,22)/t19-/m0/s1^N Key:CXGTZJYQWSUFET-IBGZPJMESA-N^N
^NY (what is this?) (verify)

The drug had completed several phase III clinical trials,[2] however in May, 2006 AstraZeneca announced that it had discontinued further development.[3]

Cardiac toxicity of tesaglitazar is related mitochondrial toxicity caused by decrease in PPARγ coactivator 1-α (PPARGC1A, PGC1α) and sirtuin 1 (SIRT1).[4]

References

Wilding JP, Gause-Nilsson I, Persson A (September 2007). "Tesaglitazar, as add-on therapy to sulphonylurea, dose-dependently improves glucose and lipid abnormalities in patients with type 2 diabetes". Diabetes & Vascular Disease Research. 4 (3): 194–203. doi:10.3132/dvdr.2007.040. PMID 17907109. S2CID 896195.
"GALIDA (tesaglitazar) Clinical Trial Report Summaries". AstraZeneca. Retrieved 2008-03-17.
"AstraZeneca Discontinues Development of GALIDA (tesaglitazar)". AstraZeneca. 2006-05-04. Retrieved 2012-07-23.
Kalliora C, Kyriazis ID, Oka SI, Lieu MJ, Yue Y, Area-Gomez E, et al. (August 2019). "Dual peroxisome-proliferator-activated-receptor-α/γ activation inhibits SIRT1-PGC1α axis and causes cardiac dysfunction". JCI Insight. 5 (17). doi:10.1172/jci.insight.129556. PMC 6777908. PMID 31393858.

Oral anti-diabetic drugs, insulins and insulin analogs, and other drugs used in diabetes (A10)

Insulins/insulin analogs

fast-acting	Insulin aspart Insulin glulisine Insulin lispro
short-acting	Regular insulin
long-acting	Insulin detemir Insulin glargine (+lixisenatide) NPH insulin Lente insulin^‡ Ultralente insulin^‡
ultra-long-acting	Insulin degludec (+insulin aspart, +liraglutide)
inhalable	Exubera^‡ Afreeza

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

Non-insulins

Insulin sensitizers

Biguanides	Buformin^‡ Metformin^# Phenformin^‡
TZDs/"glitazones" (PPAR)	Ciglitazone^§ Darglitazone^§ Englitazone^§ Lobeglitazone Netoglitazone^§ Pioglitazone Rivoglitazone^† Rosiglitazone Troglitazone^‡
Dual PPAR agonists	Aleglitazar^† Muraglitazar^§ Saroglitazar Tesaglitazar^§

Secretagogues

K⁺_ATP

Sulfonylureas	1st generation: Acetohexamide Carbutamide Chlorpropamide Glycyclamide Metahexamide Tolazamide Tolbutamide 2nd generation: Glibenclamide (glyburide) Glibornuride Glicaramide Gliclazide^# Glimepiride Glipizide Gliquidone Glisoxepide Glyclopyramide
Meglitinides/"glinides"	Mitiglinide Nateglinide Repaglinide

GLP-1 receptor agonists

DPP-4 inhibitors/"gliptins"

FFAR1 agonists

Fasiglifam^†

Other

Aldose reductase inhibitors	Epalrestat Fidarestat^§ Ranirestat^† Tolrestat^‡ Zenarestat^§
Alpha-glucosidase inhibitors	Acarbose Miglitol Voglibose
Amylin analog	Pramlintide
SGLT2 inhibitors/"gliflozins"	Canagliflozin Dapagliflozin Empagliflozin Ertugliflozin Ipragliflozin Luseogliflozin Remogliflozin^§ Sergliflozin^§ Tofogliflozin^†
Other	Benfluorex^‡ Bromocriptine

Combinations

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

PPAR modulators
PPARα	Agonists: 15-HETE 15-HpETE Aleglitazar Aluminium clofibrate Arachidonic acid Bezafibrate Clofibrate CP-775146 Daidzein DHEA (prasterone) (in rodents) Elafibranor Etomoxir Fenofibrate Genistein Gemfibrozil GW-7647 Lanifibranor Leukotriene B₄ LG-101506 LG-100754 Lobeglitazone Muraglitazar Oleylethanolamide Palmitoylethanolamide Pemafibrate Perfluorononanoic acid Perfluorooctanoic acid Pioglitazone Saroglitazar Sodelglitazar Tesaglitazar Tetradecylthioacetic acid Troglitazone WY-14643 Antagonists: GW-6471 MK-886
PPARδ	Agonists: 15-HETE 15-HpETE Arachidonic acid Bezafibrate Daidzein Elafibranor Fonadelpar Genistein GW-0742 GW-501516 L-165,041 Lanifibranor LG-101506 Seladelpar Sodelglitazar Tetradecylthioacetic acid Antagonists: FH-535 GSK-0660 GSK-3787
PPARγ	Agonists: 5-Oxo-ETE 5-Oxo-15-hydroxy-ETE 15-Deoxy-Δ^12,14-prostaglandin J₂ 15-HETE 15-HpETE Aleglitazar Arachidonic acid Balaglitazone Berberine Bezafibrate Cannabidiol Cevoglitazar Ciglitazone Daidzein Darglitazone Edaglitazone Efatutazone Englitazone Etalocib Farglitazar Genistein GW-1929 Ibuprofen Imiglitazar Indeglitazar Lanifibranor LG-100268 LG-100754 LG-101506 Lobeglitazone Muraglitazar (muroglitazar) nTZDpa Naveglitazar Netoglitazone Oxeglitazar Peliglitazar Pemaglitazar Perfluorononanoic acid Pioglitazone Prostaglandin J₂ Ragaglitazar Reglitazar Rivoglitazone Rosiglitazone RS5444 Saroglitazar Sipoglitazar Sodelglitazar Telmisartan Tesaglitazar Troglitazone SPPARMs: BADGE EPI-001 INT-131 MK-0533 S26948 Antagonists: FH-535 GW-9662 SR-202 T-0070907 Unknown: SR-1664
Non-selective	Agonists: Ciprofibrate Clinofibrate Clofibride Englitazone Etofibrate Farglitazar Netoglitazone Ronifibrate Rivoglitazone Simfibrate
See also Receptor/signaling modulators

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