Delving into the Latest Updates on MK-1832 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

MK-1832

Target

Kv1.5

Action

blockers

Mechanism

Kv1.5 blockers(Voltage-gated potassium channel subunit Kv1.5 blockers)

Therapeutic Areas

Cardiovascular Diseases

Active Indication-

Inactive Indication

Atrial Fibrillation

Originator Organization

Merck & Co., Inc.

Active Organization-

Inactive Organization

Merck & Co., Inc.

Drug Highest PhasePendingPreclinical

First Approval Date-

Regulation-

Structure/Sequence

Molecular FormulaC23H17Cl2N3O

InChIKeyZRXWXSZEIJIKNS-QHCPKHFHSA-N

CAS Registry935868-50-1

Author: Nanda, Kausik K ; Kett, Nathan R ; Manley, Peter J ; Li, Bing ; Bilodeau, Mark T ; Spencer, Robert H ; Dinsmore, Christopher J ; Lynch, Joseph J ; Wu, Zhicai ; Wolkenberg, Scott E ; Regan, Christopher P ; Trotter, B Wesley ; Stump, Gary L ; Cato, Matthew J ; White, Rebecca ; Lindsley, Craig W ; Hartman, George D ; Kane, Stefanie A ; Kiss, Laszlo ; Yeh, Suzie ; Wang, Jixin ; Nolt, M Brad

Selective inhibition of Kv1.5, which underlies the ultra-rapid delayed rectifier current, I_Kur, has been pursued as a treatment for atrial fibrillation. Here we describe the discovery of MK-1832, a Kv1.5 inhibitor with improved selectivity versus the off-target current I_Ks, whose inhibition has been associated with ventricular proarrhythmia. MK-1832 exhibits improved selectivity for I_Kur over I_Ks (>3000-fold versus 70-fold for MK-0448), consistent with an observed larger window between atrial and ventricular effects in vivo (>1800-fold versus 210-fold for MK-0448). MK-1832 also exhibits an improved preclinical pharmacokinetic profile consistent with projected once daily dosing in humans.

100 Deals associated with MK-1832

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