VX548

VX548 : Inhibitor of SCN10A

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(3 ratings)

note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars.

Information

SCN10A

Inhibitor

100 nM

Probe Availability:

MedChemExpress

In Vitro Validations

No in Vitro Validations

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): In a panel of recombinant NaV1.1 to NaV1.9 VX548 showed exquisite selectivity for NaV1.8 with at least 20000 fold difference.

Potency assay (off target): Suzetrigine is broadly selective against 180 targets in vitro, including 44 targets associated with abuse. Suzetrigine was evaluated for binding to G-protein coupled receptors, ion channels, enzymes, and transporters to evaluate the potential for off-target activity using commercially available assays. If target binding was > 50% in the screening assay, a “hit” was followed up with an assay to determine a binding IC50 and/or a functional assay IC50 (antagonism) or EC50 (agonism). (DOI: 10.1007/s40122-024-00697-0)

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

VX-548 is suitable for human cell-based studies and PK studies in rats, but I could not find efficacy data or patch clamp data on VX-548 in rats as of May 2024. It is important to note the major PK differences in male vs female rats. It is moreover not clear which side of the channel this compound acts on, so whether it should be counted as targeting an extracellular protein

(last updated: 30 May 2024 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

This is a very good compound for Nav 1.8 ion channels with very good selectivity within target class, but no information is found of selectivity outside target family. Unfortunately, no negative control or SAR studies are available in the literature.

(last updated: 3 Jun 2024 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

The high selectivity and potency of VX-548 make it an ideal tool for studying the function of the NaV1.8 channel, notably for its physiological and pathological effects at the cellular level. VX-548 has been associated with mild to moderate adverse events, and using it as a research probe can help investigate the mechanisms underlying these adverse events and identify strategies to mitigate side effects. However, this indicates that VX-548 may have off-target effects beyond ion channel proteins. Additionally, gender bias in the pharmacokinetics and metabolism of VX-548 in rats have also raised some concerns (Biopharmaceutics and Drug Disposition, 45(2), 107–114).

(last updated: 14 Jun 2024 )