ML365

• CAT Number: I005639
• CAS Number: 947914-18-3
• Molecular Formula: C22H20N2O3
• Molecular Weight: 360.41
• Purity: ≥95%
• Synonyms: 2-methoxy-N-(3-(3-methylbenzamido)phenyl)benzamide
• Target: Potassium Channel
• Solubility: 10 mM in DMSO
• Storage: Desiccate at -20C
• IC50: 4 nM/16 nM(thallium influx fluorescent assay/automated electrophysiology assay)
• IUPAC Name: 2-methoxy-N-[3-[(3-methylbenzoyl)amino]phenyl]benzamide
• InChI: InChI=1S/C22H20N2O3/c1-15-7-5-8-16(13-15)21(25)23-17-9-6-10-18(14-17)24-22(26)19-11-3-4-12-20(19)27-2/h3-14H,1-2H3,(H,23,25)(H,24,26)
• InChIKey: UTAJHKSGYJSZBR-UHFFFAOYSA-N
• SMILES: CC1=CC=CC(=C1)C(=O)NC2=CC(=CC=C2)NC(=O)C3=CC=CC=C3OC

ML365 (CAT: I005639) is a novel selective small molecule inhibitor of TASK1 (KCNK3). TASK1, also known as KCNK3, is a two-pore domain potassium channel involved in the regulation of cellular membrane potential and ion homeostasis. By inhibiting TASK1, ML365 modulates the activity of this channel, which may have implications for various physiological and pathological processes. The selective inhibition of TASK1 by ML365 can be valuable in studying the functional roles of TASK1 channels and exploring their potential as therapeutic targets in conditions such as pulmonary hypertension, cardiac arrhythmias, and neuronal disorders.

Reference

1. ML365: Development of Bis-Amides as Selective Inhibitors of the KCNK3/TASK1 Two
Pore Potassium Channel.

Zou B(1)(2), Flaherty DP(3), Simpson DS(3), Maki BE(3), Miller MR(1)(2), Shi
J(1)(2), Wu M(2), McManus OB(2), Golden JE(3), Aubé J(3)(4), Li M(1)(2).
In: Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda
(MD): National Center for Biotechnology Information (US); 2010-.
2013 Apr 15.

Author information:
(1) Johns Hopkins University, School of Medicine, The Solomon H. Snyder
Department of Neuroscience, Baltimore, MD
(2) Johns Hopkins Ion Channel Center, Baltimore, MD 21205
(3) University of Kansas Specialized Chemistry Center, Lawrence, KS 66047
(4) Department of Medicinal Chemistry, University of Kansas, Lawrence, KS 66049

Two-pore domain potassium channels play important roles in regulation of cell
membrane potential. Their activities modulate a variety of physiological
processes including immune response, hormone secretion, chemosensation, and
neuronal function. ML365 was identified as a novel selective small molecule
inhibitor of the TASK1 or potassium channel, subfamily K, member 9 (KCNK3)
two-pore domain potassium channel following a high throughput fluorescent screen
of the Molecular Libraries Small Molecule Repository (MLSMR) library and
structure activity relationship (SAR) analysis of active compounds. The
fluorescent screen measuring thallium influx through TASK1 channels was used to
identify the bisamide class of inhibitors. Chemical modification yielded a potent
and selective inhibitor, ML365. The compound blocks TASK1 channels in both the
thallium influx fluorescent assay (IC50 = 4 nM) and an automated
electrophysiology assay (IC50 = 16 nM). Based on potency differences, it
possesses more than 60-fold selectivity for inhibition of TASK1 over a
closely-related, two-pore domain potassium channel, TASK3. ML365 displays little
or no inhibition at 30 μM of more distantly related potassium channels, Kir2.1,
potassium voltage-gated channel, KQT-like subfamily, member 2 (KCNQ2), and human
ether-a go-go-related gene (hERG). Based on these criteria, ML365 is a
best-in-class probe and is a useful pharmacological probe for in vitro studies of
TASK1 function and in further studies aimed at developing therapeutic
intervention.