MSC-4381

• CAT Number: I045383
• CAS Number: 2445185-57-7
• Molecular Formula: C26H20ClN3O6S
• Molecular Weight: 537.97
• Purity: ≥95%
• Synonyms: 5-[2-[5-chloro-2-[(5-ethoxyquinolin-8-yl)sulfonylamino]phenyl]ethynyl]-4-methoxypyridine-2-carboxylic acid
• InChI: InChI=1S/C26H20ClN3O6S/c1-3-36-22-10-11-24(25-19(22)5-4-12-28-25)37(33,34)30-20-9-8-18(27)13-16(20)6-7-17-15-29-21(26(31)32)14-23(17)35-2/h4-5,8-15,30H,3H2,1-2H3,(H,31,32)
• InChIKey: FNBUZGRPJLEIMO-UHFFFAOYSA-N
• SMILES: CCOC1=C2C=CC=NC2=C(C=C1)S(=O)(=O)NC3=C(C=C(C=C3)Cl)C#CC4=CN=C(C=C4OC)C(=O)O

MSC-4381 (MCT4-IN-1) is an orally active and selective monocarboxylate transporter 4 (MCT4/SLC16A3) inhibitor with an IC50 of 77 nM and a Ki of 11 nM. MSC-4381 targets to the cytosolic domain of MCT4. MSC-4381 results in lactate efflux inhibition and reduction of cellular viability in MCT4 high expressing cells. MSC-4381 has the potential for MCT4 transporter inhibition research[1]. MSC-4381 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
MSC-4381 (compound 18n) inhibits lactate efflux in the MDA-MB-231 cell line with an IC50 of 1 nM. The on-target activity is confirmed with a Ki of 11 nM by fluorescence cross-correlation spectroscopy (FCCS)[1].
MSC-4381 does not inhibit lactate efflux to a similar extent in SNU-398 and MiaPaca2, and only 600-fold less in RT-4 cell lines[1].
MSC-4381 (compound 18n; 30 mg/kg; PO; single dose) only combined with MCT1/2 inhibitor exhibits a significant tumoral intracellular lactate accumulation[1].
MSC-4381 (30 mg/kg/day; for 15 days) shows no significant antitumor activity[1].
MSC-4381 (0.2 mg/kg; iv) has a T1/2 of 1 hours, a CL of 0.33 L/h kg, a Cmax of 489 ng/mL and a Vss of 0.4 L/kg for mice[1].

Reference

[1]. Timo Heinrich, et al. Discovery of 5-{2-[5-Chloro-2-(5-ethoxyquinoline-8-sulfonamido)phenyl]ethynyl}-4-methoxypyridine-2-carboxylic Acid, a Highly Selective in Vivo Useable Chemical Probe to Dissect MCT4 Biology. J Med Chem. 2021 Aug 26;64(16):11904-11933.
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