FABP4/5-IN-2 is a potent dual inhibitor of fatty acid binding protein 4 (FABP4) and fatty acid binding protein 5 (FABP5) that robustly interferes with intracellular lipid trafficking and fatty acid signaling pathways, making it a valuable pharmacological tool for investigating metabolic inflammation, insulin resistance, and lipid-driven disease mechanisms in both in vitro and in vivo experimental systems.

FABP4/5-IN-2 functions as a potent, dual-target competitive inhibitor of FABP4 and FABP5. The inhibitor enters this hydrophobic pocket and displaces endogenous lipids, such as arachidonic acid or palmitate, with high affinity (often exhibiting Ki values in the low nanomolar range).

In vivo, FABP4/5-IN-2 demonstrates significant efficacy in metabolic and oncogenic disease models. In ApoE-/- mice (an atherosclerosis model), dual inhibition significantly reduces foam cell formation and arterial plaque accumulation by preventing macrophages from accumulating excessive cholesterol and lipids. In obese mouse models, the treatment improves systemic insulin sensitivity and glucose tolerance by suppressing inflammation within adipose tissue. Furthermore, because FABP4 and FABP5 are highly expressed in metastatic environments, such as ovarian and prostate cancers, inhibiting these carriers restricts the fatty acid energy supply to malignant cells, thereby reducing tumor growth and metastatic potential in preclinical models.