MRTX0902

MRTX0902 : PPI of SOS1

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(1 ratings)

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Probe MRTX0902 is in the process of SERP review.

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Information

SOS1

up to 1 uM

Probe Availability:

In Vitro Validations

Uniprot ID: Q07889

Target Class: Enzyme

Target SubClass: Nucleotide

Potency: Ki

Potency Value: 1.9 nM

Potency Assay: HTRF displacement assay

PDB ID for probe-target interaction (3D structure): 7UKR

Target aliases:

Son of sevenless homolog 1, SOS1, SOS1_HUMAN, SOS- ...

DOI Reference: 10.1021/acs.jmedchem.2c00741

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay (off target): MRTX0902 was highly selective for SOS1 when compared to SOS2 and showed no inhibition of EGFR. A safety panel comprised of 78 protein targets revealed that MRTX0902 is highly selective for SOS1 (EC/IC50 > 10 μM for 74 targets).

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

To date (January 2024), five SOS1 inhibitors that block RAS activation via disruption of the RAS-SOS1 interaction are known: BAY-293 (Bayer), BI-3406 (Boehringer Ingelheim), MRTX0902 (Mirati) and compounds 13c / 37 (Wuhan University). MRTX0902 is a potent SOS1 binder with good cellular activity. It is selective in comparison to its closest homolog SOS2 as well as in comparison to EGFR and 78 protein targets from a commercial safety panel. An X-ray co-crystal structure confirms binding to SOS1. In contrast to the other published SOS1 binders, MRTX0902 contains a phthalazine core and can serve as a valuable orthogonal probe. MRTX0902 is also suitable for in vivo use. PK data for mouse, rat and dog are published. Efficacy in a MIA PaCa-2 Xenograft model was investigated as a single agent and in combination with KRAS inhibitor MRTX849 and both correlated well with downstream pERK modulation. MRTX0902 is currently being investigated in clinical trials.

(last updated: 4 Jan 2024 )