UK-5099

UK-5099 is a specific and potent mitochondrial pyruvate carrier blocker (MCK blocker). The UK5099 treated cells showed significantly higher proportion of side population (SP) fraction and expressed higher levels of stemness markers Oct3/4 and Nanog. Chemosensitivity examinations revealed that the UK5099 treated cells became more resistant to chemotherapy compared to the non-treated cells. MPC blocker (UK5099) application may be an ideal model for Warburg effect studies

Product information

CAS Number: 56396-35-1

Molecular Weight: 288.30

Formula: C18H12N2O2

Synonym:

UK 5099

UK5099

UK-5099

Chemical Name: 2-cyano-3-(1-phenyl-1H-indol-3-yl)-2-propenoic acid

Smiles: N#CC(=CC1=CN(C2=CC=CC=C12)C1C=CC=CC=1)C(O)=O

InChiKey: BIZNHCWFGNKBBZ-JLHYYAGUSA-N

InChi: InChI=1S/C18H12N2O2/c19-11-13(18(21)22)10-14-12-20(15-6-2-1-3-7-15)17-9-5-4-8-16(14)17/h1-10,12H,(H,21,22)/b13-10+

Technical Data

Appearance: Solid Power.

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

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

The trypanosomal pyruvate carrier is found to be rather insensitive to inhibition by alpha-cyano-4-hydroxycinnamate (Ki=17 mM) but can be completely blocked by UK-5099 (Ki=49 microM). UK-5099 also inhibits the monocarboxylate transporter (MCT) . UK5099 significantly inhibits the glucose-stimulated rise in oxygen consumption in a dose-dependent manner and at 150 μM reduced oxygen consumption below basal levels. UK5099 reduces ATP levels and increases ADP and AMP levels in 832/13 cells. The UK5099 treated cells show significantly higher proportion of side population fraction and express higher levels of stemness markers Oct3/4 and Nanog. UK5099 application may be an ideal model for Warburg effect studies.

In Vivo:

The MPC inhibitor UK5099 increases the glucose excursion seen during an intraperitoneal glucose tolerance test in C57BLK mice.

References:

1. Jourdain P, Allaman I, Rothenfusser K, Fiumelli H, Marquet P, Magistretti PJ. L-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade. Sci Rep. 2016 Feb 19;6:21250. doi: 10.1038/srep21250. PubMed PMID: 26893204; PubMed Central PMCID: PMC4759786.
2. Zhong Y, Li X, Yu D, Li X, Li Y, Long Y, Yuan Y, Ji Z, Zhang M, Wen JG, Nesland JM, Suo Z. Application of mitochondrial pyruvate carrier blocker UK5099 creates metabolic reprogram and greater stem-like properties in LnCap prostate cancer cells in vitro. Oncotarget. 2015 Nov 10;6(35):37758-69. doi: 10.18632/oncotarget.5386. PubMed PMID: 26413751; PubMed Central PMCID: PMC4741963.
3. Patterson JN, Cousteils K, Lou JW, Manning Fox JE, MacDonald PE, Joseph JW. Mitochondrial metabolism of pyruvate is essential for regulating glucose-stimulated insulin secretion. J Biol Chem. 2014 May 9;289(19):13335-46. doi: 10.1074/jbc.M113.521666. Epub 2014 Mar 27. PubMed PMID: 24675076; PubMed Central PMCID: PMC4036342.

Products are for research use only. Not for human use.