5.33436

Monocarboxylate Transport Inhibitor, AR-C155858

• Synonym(e): Monocarboxylate Transport Inhibitor, AR-C155858, (S)-6-((3,5-dimethyl-1H-pyrazol-4-yl)methyl)-5-(4-hydroxyisoxazolidine-2-carbonyl)-1-isobutyl-3-methylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione , Monocarboxylate transporter 1 inhibitor, AR-C155858, SR13801
• Empirische Formel (Hill-System): C₂₁H₂₇N₅O₅S
• CAS-Nummer: 496791-37-8
• Molekulargewicht: 461.53
• MDL number: MFCD22124476
• UNSPSC Code: 12352200
• NACRES: NA.77
• Assay: ≥95% (HPLC)
• Form: solid
• Storage condition: OK to freeze, protect from light

Eigenschaften

• assay: ≥95% (HPLC)
• Quality Segment: 100
• form: solid
• potency: 1.2 nM K_i
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze, protect from light
• color: brown
• solubility: DMSO: 50 mg/mL
• storage temp.: −20°C
• SMILES string: [s]1c2[n]([c]([n]([c](c2c(c1Cc4c([nH]nc4C)C)C(=O)N3OC[C@H](C3)O)=O)C)=O)CC(C)C
• InChI: 1S/C21H27N5O5S/c1-10(2)7-25-20-17(18(28)24(5)21(25)30)16(19(29)26-8-13(27)9-31-26)15(32-20)6-14-11(3)22-23-12(14)4/h10,13,27H,6-9H2,1-5H3,(H,22,23)/t13-/m0/s1
• InChI key: ISIVOJWVBJIOFM-ZDUSSCGKSA-N

Beschreibung

General description

A cell-permeable thieno[2,3-d]pyrimidinedione compound that acts as a highly potent inhibitor of monocarboxylate transporter 1 (MCT1; K_i = 2.3 nM for lactate uptake in rat erythrocytes). Also shown to inhibit MCT2 when associated with basigin (IC₅₀ = 10 nM). Does not affect the activity of MCT4 even at higher concentration. Also shown to block MCT1 expressed in Xenopus oocytes Binds to MCT1 from the intracellular side involving transmembrane helices 7-10. Its inhibitory effect is significantly reduced with either F360Y or S364G mutations (~100 nM) and the inhibitory effect is lost with both sites are mutated (~5 µM). Displays high metabolic stability and low inhibition of CYP. Shown to block lactate transport and increase intracellular lactate levels in Raji Burkitt and MCF-7 cells and reduces their proliferation.

Monocarboxylate Transport Inhibitor, AR-C155858, CAS 496791-37-8, is a cell-permeable, potent inhibitor of monocarboxylate transporter 1 (MCT1; K_i = 2.3 nM for lactate uptake in rat erythrocytes).

Biochem/physiol Actions

Cell permeable: yes

Primary Target
MCT1

Preparation Note

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Other Notes

Nancolas, B., et al. 2015. Biochem. J.467, 192.
Ovens, M. J. et al. 2010. Biochem. J.425, 523.
Guile, S. D., et al. 2007. J. Med. Chem.50, 254.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Disclaimer

Toxicity: Standard Handling (A)

Sicherheitshinweise

• Lagerklasse: 11 - Combustible Solids
• wgk: WGK 3
• flash_point_f: Not applicable
• flash_point_c: Not applicable