Farglitazar

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 326989

CAS#: 196808-45-4

Description: Farglitazar, also known as GI-262570, is a PPAR-γ agonist potentially for the treatment of type 2 diabetes. GI262570 can increase water and sodium reabsorption in distal nephron by stimulating the ENaC and Na,K-ATPase system.


Price and Availability

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Farglitazar is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 326989
Name: Farglitazar
CAS#: 196808-45-4
Chemical Formula: C34H30N2O5
Exact Mass: 546.2155
Molecular Weight: 546.623
Elemental Analysis: C, 74.71; H, 5.53; N, 5.12; O, 14.63


Synonym: Farglitazar; GI-262570; GI 262570; GI262570.

IUPAC/Chemical Name: (S)-2-((2-benzoylphenyl)amino)-3-(4-(2-(5-methyl-2-phenyloxazol-4-yl)ethoxy)phenyl)propanoic acid

InChi Key: ZZCHHVUQYRMYLW-HKBQPEDESA-N

InChi Code: InChI=1S/C34H30N2O5/c1-23-29(36-33(41-23)26-12-6-3-7-13-26)20-21-40-27-18-16-24(17-19-27)22-31(34(38)39)35-30-15-9-8-14-28(30)32(37)25-10-4-2-5-11-25/h2-19,31,35H,20-22H2,1H3,(H,38,39)/t31-/m0/s1

SMILES Code: O=C(O)[C@H](CC1=CC=C(OCCC2=C(C)OC(C3=CC=CC=C3)=N2)C=C1)NC4=CC=CC=C4C(C5=CC=CC=C5)=O


Technical Data

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


References

1: Otake K, Azukizawa S, Takeda S, Fukui M, Kawahara A, Kitao T, Shirahase H. Novel 2,7-Substituted (S)-1,2,3,4-Tetrahydroisoquinoline-3-carboxylic Acids: Peroxisome Proliferator-Activated Receptor γ Partial Agonists with Protein-Tyrosine Phosphatase 1B Inhibition. Chem Pharm Bull (Tokyo). 2015;63(12):998-1014. doi: 10.1248/cpb.c15-00508. PubMed PMID: 26633022.

2: Ma Y, Wang SQ, Xu WR, Wang RL, Chou KC. Design novel dual agonists for treating type-2 diabetes by targeting peroxisome proliferator-activated receptors with core hopping approach. PLoS One. 2012;7(6):e38546. doi: 10.1371/journal.pone.0038546. Epub 2012 Jun 7. PubMed PMID: 22685582; PubMed Central PMCID: PMC3369836.

3: Yamagishi K, Yamamoto K, Mochizuki Y, Nakano T, Yamada S, Tokiwa H. Flexible ligand recognition of peroxisome proliferator-activated receptor-gamma (PPARgamma). Bioorg Med Chem Lett. 2010 Jun 1;20(11):3344-7. doi: 10.1016/j.bmcl.2010.04.031. Epub 2010 Apr 14. PubMed PMID: 20444603.

4: McHutchison J, Goodman Z, Patel K, Makhlouf H, Rodriguez-Torres M, Shiffman M, Rockey D, Husa P, Chuang WL, Levine R, Jonas M, Theodore D, Brigandi R, Webster A, Schultz M, Watson H, Stancil B, Gardner S; Farglitizar Study Investigators. Farglitazar lacks antifibrotic activity in patients with chronic hepatitis C infection. Gastroenterology. 2010 Apr;138(4):1365-73, 1373.e1-2. doi: 10.1053/j.gastro.2009.12.003. Epub 2010 Feb 13. Erratum in: Gastroenterology. 2010 Jul;139(1):360. PubMed PMID: 20004661.

5: Tomillero A, Moral MA. Gateways to clinical trials. Methods Find Exp Clin Pharmacol. 2009 Apr;31(3):183-226. PubMed PMID: 19536362.

6: Nofziger C, Brown KK, Smith CD, Harrington W, Murray D, Bisi J, Ashton TT, Maurio FP, Kalsi K, West TA, Baines D, Blazer-Yost BL. PPARgamma agonists inhibit vasopressin-mediated anion transport in the MDCK-C7 cell line. Am J Physiol Renal Physiol. 2009 Jul;297(1):F55-62. doi: 10.1152/ajprenal.00090.2009. Epub 2009 Apr 29. PubMed PMID: 19403648.

7: Lee BC, Dence CS, Zhou H, Parent EE, Welch MJ, Katzenellenbogen JA. Fluorine-18 labeling and biodistribution studies on peroxisome proliferator-activated receptor-gamma ligands: potential positron emission tomography imaging agents. Nucl Med Biol. 2009 Feb;36(2):147-53. doi: 10.1016/j.nucmedbio.2008.11.002. PubMed PMID: 19217526; PubMed Central PMCID: PMC2774759.

8: Azukizawa S, Kasai M, Takahashi K, Miike T, Kunishiro K, Kanda M, Mukai C, Shirahase H. Synthesis and biological evaluation of (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids: a novel series of PPAR gamma agonists. Chem Pharm Bull (Tokyo). 2008 Mar;56(3):335-45. PubMed PMID: 18310946.

9: Spraggs C, McCarthy A, McCarthy L, Hong G, Hughes A, Lin X, Sathe G, Smart D, Traini C, Van Horn S, Warren L, Mosteller M. Genetic variants in the epithelial sodium channel associate with oedema in type 2 diabetic patients receiving the peroxisome proliferator-activated receptor gamma agonist farglitazar. Pharmacogenet Genomics. 2007 Dec;17(12):1065-76. PubMed PMID: 18004211.

10: Trump RP, Cobb JE, Shearer BG, Lambert MH, Nolte RT, Willson TM, Buckholz RG, Zhao SM, Leesnitzer LM, Iannone MA, Pearce KH, Billin AN, Hoekstra WJ. Co-crystal structure guided array synthesis of PPARgamma inverse agonists. Bioorg Med Chem Lett. 2007 Jul 15;17(14):3916-20. Epub 2007 May 18. PubMed PMID: 17533125.

11: Yang B, Chen L, Qian Y, Triantafillou JA, McNulty JA, Carrick K, Clifton LG, Han B, Geske R, Strum J, Brown KK, Stimpson SA, Pahel G. Changes of skeletal muscle adiponectin content in diet-induced insulin resistant rats. Biochem Biophys Res Commun. 2006 Mar 3;341(1):209-17. Epub 2006 Jan 9. PubMed PMID: 16414018.

12: Tenenbaum A, Motro M, Fisman EZ. Dual and pan-peroxisome proliferator-activated receptors (PPAR) co-agonism: the bezafibrate lessons. Cardiovasc Diabetol. 2005 Sep 16;4:14. Review. PubMed PMID: 16168052; PubMed Central PMCID: PMC1236941.

13: Yang B, Lin P, Carrick KM, McNulty JA, Clifton LG, Winegar DA, Strum JC, Stimpson SA, Pahel GL. PPARgamma agonists diminish serum VEGF elevation in diet-induced insulin resistant SD rats and ZDF rats. Biochem Biophys Res Commun. 2005 Aug 19;334(1):176-82. PubMed PMID: 15993383.

14: Golfman LS, Wilson CR, Sharma S, Burgmaier M, Young ME, Guthrie PH, Van Arsdall M, Adrogue JV, Brown KK, Taegtmeyer H. Activation of PPARgamma enhances myocardial glucose oxidation and improves contractile function in isolated working hearts of ZDF rats. Am J Physiol Endocrinol Metab. 2005 Aug;289(2):E328-36. Epub 2005 Mar 29. PubMed PMID: 15797988.

15: Sheu SH, Kaya T, Waxman DJ, Vajda S. Exploring the binding site structure of the PPAR gamma ligand-binding domain by computational solvent mapping. Biochemistry. 2005 Feb 1;44(4):1193-209. PubMed PMID: 15667213.

16: Chen Q, Chen J, Sun T, Shen J, Shen X, Jiang H. A yeast two-hybrid technology-based system for the discovery of PPARgamma agonist and antagonist. Anal Biochem. 2004 Dec 15;335(2):253-9. PubMed PMID: 15556564.

17: Yang B, Brown KK, Chen L, Carrick KM, Clifton LG, McNulty JA, Winegar DA, Strum JC, Stimpson SA, Pahel GL. Serum adiponectin as a biomarker for in vivo PPARgamma activation and PPARgamma agonist-induced efficacy on insulin sensitization/lipid lowering in rats. BMC Pharmacol. 2004 Oct 18;4:23. PubMed PMID: 15491498; PubMed Central PMCID: PMC526775.

18: Chen L, Yang B, McNulty JA, Clifton LG, Binz JG, Grimes AM, Strum JC, Harrington WW, Chen Z, Balon TW, Stimpson SA, Brown KK. GI262570, a peroxisome proliferator-activated receptor {gamma} agonist, changes electrolytes and water reabsorption from the distal nephron in rats. J Pharmacol Exp Ther. 2005 Feb;312(2):718-25. Epub 2004 Oct 8. PubMed PMID: 15475592.

19: Heppner TJ, Bonev AD, Eckman DM, Gomez MF, Petkov GV, Nelson MT. Novel PPARgamma agonists GI 262570, GW 7845, GW 1929, and pioglitazone decrease calcium channel function and myogenic tone in rat mesenteric arteries. Pharmacology. 2005 Jan;73(1):15-22. Epub 2004 Sep 27. PubMed PMID: 15452359.

20: Gardiner SM, Nunez DJ, Baer PG, Brown KK, Bennett T. Regional hemodynamic effects of the N-(2-benzoylphenyl)-L-tyrosine peroxisome proliferator-activated receptor-gamma ligand, GI 262570 [(S)-2-(2-benzoylphenylamino)-3-[4-[2-(5-methyl-2-phenyl-2-oxazol-4-yl)ethoxy]phe nyl]propionic acid], in conscious rats. J Pharmacol Exp Ther. 2004 Sep;310(3):1226-33. Epub 2004 May 4. PubMed PMID: 15126643.