GW4064

Overview

GW4064 is a synthetic, non-steroidal agonist of the farnesoid X receptor (NR1H4 / FXR). It is primarily used as a pharmacological tool compound to probe FXR-mediated signaling. Activation of FXR by GW4064 engages the SHP/LRH-1 axis, suppressing STAT3 phosphorylation and BCL2L1 (Bcl-xL)-mediated survival in CCA cell lines.

Evidence in the corpus

• FXR activation by GW4064 (or the clinical compound obeticholic acid) suppresses CCA proliferation and migration via SHP-mediated STAT3 inhibition and downregulation of BCL2L1 (Bcl-xL); heterogeneous FXR expression across CCA subtypes limits single-agent efficacy PMID:25608663

Resistance mechanisms

• Low FXR expression (H-score <120) in pCCA/dCCA is an intrinsic resistance mechanism; DNMT inhibitor combinations proposed to restore FXR activity PMID:25608663

Cancer types (linked)

• CHOL — cholangiocarcinoma

Sources

• PMID:25608663

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