PF-04991532
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MedKoo CAT#: 522525

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.

Chemical Structure

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PF-04991532
CAS# 1215197-37-7
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 522525
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

Price and Availability

Size Price Availability Quantity
5mg USD 220 2 Weeks
25mg USD 565 2 Weeks
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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:

Product Data:
Product Data
Instruction:
View handling instruction
Biological target: PF-04991532 is a potent, hepatoselective glucokinase activator with EC50s of 80 and 100 nM in human and rat, respectively.
In vitro activity: TBD
In vivo activity: In these studies, PF-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. During a hyperglycemic clamp in Goto-Kakizaki rats, the glucose infusion rate was increased approximately 5-fold with PF-04991532. This increase in glucose infusion can be partially attributed to the 60% reduction in endogenous glucose production. While PF-04991532 induced dose-dependent increases in plasma triglyceride concentrations it had no effect on hepatic triglyceride concentrations in Goto-Kakizaki rats. Interestingly, PF-04991532 decreased intracellular AMP concentrations and increased hepatic futile cycling. Reference: PLoS One. 2014 May 23;9(5):e97139. https://pubmed.ncbi.nlm.nih.gov/24858947/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 125.0 315.36

Preparing Stock Solutions

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.

Recalculate based on batch purity %
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: 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. PMID: 24858947; PMCID: PMC4032240.
In vitro protocol: TBD
In vivo protocol: 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. PMID: 24858947; PMCID: PMC4032240.

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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.