[CAS NO. 475479-34-6] Aleglitazar
PRODUCTS SPECIFICATIONS [475479-34-6]
DESCRIPTION [475479-34-6]
Overview
| MDL | MFCD09954107 |
|---|---|
| Molecular Weight | 437.51 |
| Molecular Formula | C24H23NO5S |
| SMILES | CC1=C(CCOC2=CC=C(C[C@@H](C(O)=O)OC)C3=C2C=CS3)N=C(C4=CC=CC=C4)O1 |
Summary
IC50 & Target
|
PPARγ 19 nM (IC 50 ) |
PPARα 38 nM (IC 50 ) |
In Vitro
Aleglitazar exhibits species selectivity with respect to PPARα, with an EC
50
s of 50 nM, 2.26 µM and 2.34 µM for human PPARα, rat PPARα and mouse PPARα, respectively
[1]
.
Aleglitazar (0.01-40 µM; 12-48 hours) does not significantly increase lactate dehydrogenase (LDH) release at concentrations of 0.1 µM to 20 µM, but significant increases LDH release at concentrations of 30 µM and 40 µM
[2]
.
Aleglitazar (0.01-20 µM; 48 hours) decreases hyperglycaemic conditions (HG, glucose 25 mM)-induced apoptosis, caspase-3 activity and cytochrome-C release
[2]
.
Aleglitazar improves cell viability in cells exposed to hyperglycaemia
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Cytotoxicity Assay [2]
| Cell Line: | human cardiomyocytes (HCM), wild-type mice cardiomyocytes (mCM-WT) |
| Concentration: | 0.01 µM, 0.05 µM, 0.1 µM, 0.5 µM, 1 µM, 5 µM, 10 µM, 20 µM, 30 µM, 40 µM |
| Incubation Time: | 12 hours, 24 hours, 48 hours |
| Result: | Increased LDH release at concentrations of 30 µM and 40 µM. |
Apoptosis Analysis [2]
| Cell Line: | HCM, mCM-WT |
| Concentration: | 0.01 µM, 0.05 µM, 0.1 µM, 0.5 µM, 1 µM, 5 µM, 10 µM, 20 µM |
| Incubation Time: | 48 hours |
| Result: | Dose dependently decreased apoptosis, caspase-3 activity and cytochrome-C release induced by HG. |
In Vivo
Aleglitazar (0.3-3.0 mg/kg; i.p.; daily; for 7 days) exerts beneficial effects on structural and functional outcomes of mild brain ischemia
[3]
.
Aleglitazar reduces key aspects of microglia activation including NO production, release of proinflammatory cytokines, migration, and phagocytosis
[3]
.
Aleglitazar attenuates inflammatory responses in post-ischemic brain
[3]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Male 129S6/SvEv mice (24-30 g), middle cerebral artery occlusion (MCAo) models [3] |
| Dosage: | 0.3 mg/kg, 3.0 mg/kg |
| Administration: | Intraperitoneal injection, daily, for 7 days |
| Result: | Reduced the size of the ischemic lesion as assessed using NeuN immunohistochemistry on day 7. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT00461006 | Hoffmann-La Roche |
Diabetes Mellitus Type 2
|
June 2007 | Phase 2 |
| NCT01691989 | Hoffmann-La Roche |
Diabetes Mellitus Type 2
|
December 2012 | Phase 3 |
| NCT01197911 | Hoffmann-La Roche |
Healthy Volunteer
|
September 2010 | Phase 1 |
| NCT01398267 | Hoffmann-La Roche |
Diabetes Mellitus Type 2
|
August 2011 | Phase 1 |
| NCT01715818 | Hoffmann-La Roche |
Cardiovascular Disease, Diabetes Mellitus Type 2
|
December 2012 | Phase 3 |
| NCT01893242 | Hoffmann-La Roche |
Diabetes Mellitus Type 2, Kidney Disease, Chronic
|
December 2013 | Phase 3 |
| NCT01188317 | Hoffmann-La Roche |
Healthy Volunteer
|
June 2010 | Phase 1 |
| NCT01615354 | Hoffmann-La Roche |
Healthy Volunteer
|
July 2012 | Phase 1 |
| NCT01871415 | Hoffmann-La Roche |
Diabetes Mellitus Type 2
|
May 2013 | Phase 3 |
| NCT00461058 | Hoffmann-La Roche |
Diabetes Mellitus Type 2
|
May 2007 | Phase 2 |
| NCT01691755 | Hoffmann-La Roche |
Diabetes Mellitus Type 2
|
November 2012 | Phase 3 |
| NCT01188304 | Hoffmann-La Roche |
Healthy Volunteer
|
July 2010 | Phase 1 |
| NCT01679639 | Hoffmann-La Roche |
Healthy Volunteer
|
August 2012 | Phase 1 |
| NCT01043029 | Hoffmann-La Roche |
Diabetes Mellitus Type 2
|
May 2010 | Phase 2 |
| NCT01701739 | Hoffmann-La Roche |
Healthy Volunteer
|
October 2012 | Phase 1 |
| NCT01729403 | Hoffmann-La Roche |
Diabetes Mellitus Type 2
|
December 2012 | Phase 2 |
| NCT01711775 | Hoffmann-La Roche |
Healthy Volunteer
|
November 2012 | Phase 1 |
| NCT01042769 | Hoffmann-La Roche |
Diabetes Mellitus Type 2
|
February 2010 | Phase 3 |
| NCT00388518 | Hoffmann-La Roche |
Diabetes Mellitus Type 2
|
November 2006 | Phase 2 |
| NCT01680978 | Hoffmann-La Roche |
Diabetes Mellitus Type 2
|
October 2012 | Phase 2 |
| NCT01871428 | Hoffmann-La Roche |
Diabetes Mellitus Type 2
|
June 2013 | Phase 3 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 50 mg/mL ( 114.28 mM )
* "≥" means soluble, but saturation unknown.
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.2857 mL | 11.4283 mL | 22.8566 mL |
| 5 mM | 0.4571 mL | 2.2857 mL | 4.5713 mL |
| 10 mM | 0.2286 mL | 1.1428 mL | 2.2857 mL |
-
1.
-
2.
Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (5.71 mM); Clear solution
References
- [1] Bénardeau A, Benz J, Binggeli A, et al. Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. Bioorg Med Chem Lett. 2009 May 1;19(9):2468-73.
- [2] Yan Chen, et al. Aleglitazar, a dual peroxisome proliferator-activated receptor-α and -γ agonist, protects cardiomyocytes against the adverse effects of hyperglycaemia. Diab Vasc Dis Res. 2017 Mar; 14(2): 152–162.
- [3] Valérie Boujon, et al. Dual PPARα/γ agonist aleglitazar confers stroke protection in a model of mild focal brain ischemia in mice. J Mol Med (Berl). 2019; 97(8): 1127-1138.
Synonyms
