GtoPdb is requesting financial support from commercial users. Please see our sustainability page for more information.

MRT-6160   Click here for help

GtoPdb Ligand ID: 14337

Synonyms: compound 161 [WO2024151547A1] | MRT6160
Compound class: Synthetic organic
Comment: MRT-6160 is a cereblon-based molecular glue degrader. It is designed to target the Rho-family guanine nucleotide exchange factor (GEF) and adaptor protein VAV1 as a neosubstrate [3]. VAV1 is a key signaling protein downstream of both the T- and B-cell receptors that is proposed as a novel target for immunomodulator development for the treatment of hematological malignancies and autoimmune diseases [1-2,4]. Selective degradation is proposed to disrupt the GEF and scaffolding activities of VAV1.
2D Structure
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 3
Topological polar surface area 66.48
Molecular weight 392.84
XLogP 0.88
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

✖
Canonical SMILES C1=CC(=O)N(C=C1)C2=CC=C(C=C2)C3=C(C(=CC=C3)C4CCC(=O)NC4=O)Cl
Isomeric SMILES C1CC(=O)NC(=O)C1C2=CC=CC(=C2Cl)C3=CC=C(C=C3)N4C=CC=CC4=O
InChI InChI=1S/C22H17ClN2O3/c23-21-16(4-3-5-17(21)18-11-12-19(26)24-22(18)28)14-7-9-15(10-8-14)25-13-2-1-6-20(25)27/h1-10,13,18H,11-12H2,(H,24,26,28)
InChI Key RIFDPWJLHNZGEX-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Ksionda O, Saveliev A, Köchl R, Rapley J, Faroudi M, Smith-Garvin JE, Wülfing C, Rittinger K, Carter T, Tybulewicz VL. (2012)
Mechanism and function of Vav1 localisation in TCR signalling.
J Cell Sci, 125 (Pt 22): 5302-14. [PMID:22956543]
2. Lin H, Yu X, Haiyang, Cheng R, Qi X, Yang YY, Zhou S, Che X, Wang J. (2025)
Beyond the G-Loop: CRBN Molecular Glues Potently Target VAV1 via a Novel SH3 RT-Loop Degron.
bioRxiv, Preprint. [PMID:40661494]
3. Mcallister LA, Liardo E, Ritzen A, Oleinikovas V, Cabre XL, Fasching B, Bizzini LD, Lesieur M. (2024)
Targeted degradation of vav1.
Patent number: WO2024151547A1. Assignee: Monte Rosa Therapeutics Inc. Priority date: 08/01/2024. Publication date: 18/07/2024.
4. Neurath MF, Berg LJ. (2024)
VAV1 as a putative therapeutic target in autoimmune and chronic inflammatory diseases.
Trends Immunol, 45 (8): 580-596. [PMID:39060140]