Work

Identification of an SFRP1 inhibitor as a potential therapeutic strategy for cancers using dry-wet combined drug discovery strategy

Year: 2026

Type: article

Abstract: Secreted frizzled-related protein 1 (SFRP1) exerts a context-dependent dual role in cancer, and its epigenetic silencing drives pro-tumorigenic non-canonical Wnt activation, a promising therapeutic target for advanced malignancies. In this study, a validated 3D SFRP1 model was built by comprehensive computational approach. High-throughput virtual screening of a commercial compound library identified a common core scaffold, which was rationally design to synthesize lead compound. The target molecule was synthesized via organic synthetic approaches. Surface plasmon resonance (SPR) assays confirmed the specific binding of compound L1 to SFRP1 with a dissociation constant (KD) of 79.1 nM. Furthermore, molecular docking and molecular dynamics (MD) simulation elucidated the interaction between compound L1 and SFRP1 at the molecular level and in physiological conditions.

Source: Molecular Diversity

DOI: 10.1007/s11030-026-11586-3

Authors: Yunlong Zhang, Ruiqi Wei, Meihong Pan, Nan Qin, Xiaopeng Wei, Jun Shen

Institutions: Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University

Language: English

Topic: Computational Drug Discovery Methods

Subfield: Drug Discovery

Field: Pharmacology, Toxicology and Pharmaceutics

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

OpenAlex ID: W7162509783