MASTL-IN-1

MASTL-IN-1 : Inhibitor of MASTL

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

MASTL

Inhibitor

up to 100 nM

In Vitro Validations

Uniprot ID: Q96GX5

Target Class: Kinase

Target SubClass: AGC

Potency: Ki

Potency Value: 0.03 nM

Potency Assay: Biochemical assay

PDB ID for probe-target interaction (3D structure): --

Target aliases:

Serine/threonine-protein kinase greatwall, THC2, M ...

DOI Reference: 10.1021/acs.jmedchem.4c01659

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): MASTL-IN-15 was profiled against a panel of 394 kinases for percent inhibition at 100 nM (>3,000x over MASTL biochemical Ki). Only 22/394 kinases assayed showed >80% inhibition at that dose. MASTL-IN-15 was considered to be highly selective given its potent biochemical activity against MASTL. The 22 inhibited kinases were further assessed for biochemical IC50, and only eight had the potential to be inhibited at less than a 100-fold window relative to MASTL. Further, out of the eight, only one had the potential to be inhibited at less than 50-fold relative to MASTL: MAP4K4.

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Currently, this probe has been used in a single publication. While the data provided in this publication is generally promising, independent validation is needed in order to recommend this probe for future use. Additionally, in the one existing publication, the authors do not demonstrate that a point mutation in the drug's target is sufficient to confer resistance to the compound.

(last updated: 16 Dec 2024 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Highly potent inhibitor of MASTL with excellent (>50 fold) selectivity in a kinase screen. Target engagement in cells confirmed via S67 phosphorylation. No cytoxocity data provided.

(last updated: 19 Dec 2024 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

MASTL-IN-1 is highly potent (Ki <0.03 nM). The recommended cellular dose (10 nM; and <100 nM) should be followed to observe the compound's selectivity. In vivo study showed the IC90 could be covered sufficiently for once daily dosing. 30 mg/Kg QD appears to be approaching maximum tolerated dose as judged by body weight loss.

(last updated: 27 Jan 2025 )