9QFF

Structure of SOS1 in complex with compound 3

This is a non-PDB format compatible entry.

Summary for 9QFF

• Entry DOI: 10.2210/pdb9qff/pdb
• Descriptor: Son of sevenless homolog 1, 3-[[3-(trifluoromethyl)phenyl]methyl]-2~{H}-1$l^{6},2,4-benzothiadiazine 1,1-dioxide (3 entities in total)
• Functional Keywords: gef, cytosolic protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 57716.96

Authors

Breed, J. (deposition date: 2025-03-11, release date: 2025-09-17, Last modification date: 2025-11-05)

Primary citation

Bonomo, S.,Gibault, F.,Bagal, S.K.,Blackwell, J.H.,Breed, J.,Collie, G.W.,Couturier, M.,Diene, C.,Di Fruscia, P.,Gray, S.,Hughes, C.,Jeyaharan, D.,Kettle, J.G.,Milbradt, A.G.,Northall, S.,Peters, K.,Stubbs, C.J.,Underwood, E.,Chen, Y.,Hao, H.,Lainchbury, M.D.
Focused Structure-Based Virtual Screening Identifies Novel Inhibitors of SOS1.
Acs Med.Chem.Lett., 16:1905-1909, 2025

PubMed Abstract: SOS1 is one of the key regulators of KRAS where it catalyzes the GTP-to-GDP turnover required for KRAS activation. Inhibition of the SOS1::KRAS interaction is an attractive strategy to modulate abnormal KRAS activation, which is responsible for several malignancies. In this work, we performed a virtual screening campaign on the AstraZeneca compound collection with Heavy Atom Count between 21 and 26 and identified two novel and efficient binders of SOS1 which fulfill the minimal pharmacophoric requirements disclosed in known compounds. Subsequently, structure- and knowledge-based approaches were applied to develop these binders into functional inhibitors of SOS1.

PubMed: 41089494
DOI: 10.1021/acsmedchemlett.5c00302

Experimental method

X-RAY DIFFRACTION (1.879 Å)