WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H522525
CAS#: 1215197-37-7
Description: PF-04991532 is a potent and selective hepatoselective glucokinase activator. PF-04991532 ameliorates hyperglycemia without causing hepatic steatosis in diabetic rats. F-04991532 reduced plasma glucose concentrations independent of changes in insulin concentrations in a dose-dependent manner both acutely and after 28 days of sub-chronic treatment. PF-04991532 may offer glycemic control without inducing hepatic steatosis supporting the evaluation of tissue specific activators in clinical trials.
Hodoodo Cat#: H522525
Name: PF-04991532
CAS#: 1215197-37-7
Chemical Formula: C18H19F3N4O3
Exact Mass: 396.14
Molecular Weight: 396.370
Elemental Analysis: C, 54.54; H, 4.83; F, 14.38; N, 14.14; O, 12.11
Synonym: PF-04991532; PF 04991532; PF04991532; PF-4991532; PF4991532; PF 4991532.
IUPAC/Chemical Name: (S)-6-(3-Cyclopentyl-2-(4-(trifluoromethyl)-1H-imidazol-1-yl)propanamido)nicotinic Acid
InChi Key: GKMLFBRLRVQVJO-ZDUSSCGKSA-N
InChi Code: InChI=1S/C18H19F3N4O3/c19-18(20,21)14-9-25(10-23-14)13(7-11-3-1-2-4-11)16(26)24-15-6-5-12(8-22-15)17(27)28/h5-6,8-11,13H,1-4,7H2,(H,27,28)(H,22,24,26)/t13-/m0/s1
SMILES Code: O=C(O)C1=CN=C(NC([C@@H](N2C=C(C(F)(F)F)N=C2)CC3CCCC3)=O)C=C1
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, not in water
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).
HS Tariff Code: 2934.99.9001
More Info:
Biological target: | |
In vitro activity: | |
In vivo activity: |
The following data is based on the product molecular weight 396.37 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
---|---|---|---|
1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
Formulation protocol: | |
In vitro protocol: | |
In vivo protocol: |
1: Sharma R, Litchfield J, Bergman A, Atkinson K, Kazierad D, Gustavson SM, Di L,
Pfefferkorn JA, Kalgutkar AS. Comparison of the circulating metabolite profile of
PF-04991532, a hepatoselective glucokinase activator, across preclinical species
and humans: potential implications in metabolites in safety testing assessment.
Drug Metab Dispos. 2015 Feb;43(2):190-8. doi: 10.1124/dmd.114.061218. Epub 2014
Nov 10. PubMed PMID: 25384899.
2: Ghosh A, Maurer TS, Litchfield J, Varma MV, Rotter C, Scialis R, Feng B, Tu M,
Guimaraes CR, Scott DO. Toward a unified model of passive drug permeation II: the
physiochemical determinants of unbound tissue distribution with applications to
the design of hepatoselective glucokinase activators. Drug Metab Dispos. 2014
Oct;42(10):1599-610. doi: 10.1124/dmd.114.058032. Epub 2014 Jul 14. PubMed PMID:
25024402.
3: Erion DM, Lapworth A, Amor PA, Bai G, Vera NB, Clark RW, Yan Q, Zhu Y, Ross
TT, Purkal J, Gorgoglione M, Zhang G, Bonato V, Baker L, Barucci N, D'Aquila T,
Robertson A, Aiello RJ, Yan J, Trimmer J, Rolph TP, Pfefferkorn JA. The
hepatoselective glucokinase activator PF-04991532 ameliorates hyperglycemia
without causing hepatic steatosis in diabetic rats. PLoS One. 2014 May
23;9(5):e97139. doi: 10.1371/journal.pone.0097139. eCollection 2014. PubMed PMID:
24858947; PubMed Central PMCID: PMC4032240.
4: Pfefferkorn JA, Guzman-Perez A, Litchfield J, Aiello R, Treadway JL, Pettersen
J, Minich ML, Filipski KJ, Jones CS, Tu M, Aspnes G, Risley H, Bian J, Stevens
BD, Bourassa P, D'Aquila T, Baker L, Barucci N, Robertson AS, Bourbonais F,
Derksen DR, Macdougall M, Cabrera O, Chen J, Lapworth AL, Landro JA, Zavadoski
WJ, Atkinson K, Haddish-Berhane N, Tan B, Yao L, Kosa RE, Varma MV, Feng B,
Duignan DB, El-Kattan A, Murdande S, Liu S, Ammirati M, Knafels J,
Dasilva-Jardine P, Sweet L, Liras S, Rolph TP. Discovery of
(S)-6-(3-cyclopentyl-2-(4-(trifluoromethyl)-1H-imidazol-1-yl)propanamido)nicotini
c acid as a hepatoselective glucokinase activator clinical candidate for treating
type 2 diabetes mellitus. J Med Chem. 2012 Feb 9;55(3):1318-33. doi:
10.1021/jm2014887. Epub 2012 Jan 24. PubMed PMID: 22196621.