dock2

CPYPP is an inhibitor of DOCK2-Rac1 interaction. CPYPP binds to DOCK2 DHR-2 domain and inhibits the guanine nucleotide exchange factor (GEF) activity of DOCK2DHR-2 for Rac1 in a dose-dependent manner(IC50 : 22.8 µM). CPYPP also inhibits DOCK180, DOCK5 and

DOCK2-IN-1, an analogue of CPYPP, effectively inhibits DOCK2 (IC50 = 19.1 μM) by reversibly binding to its DHR-2 domain, thereby hindering its catalytic function. This compound obstructs the activation of Rac in lymphocytes, triggered either by chemokine or antigen receptors. Consequently, DOCK2-IN-1 markedly reduces chemotactic responses and T cell activation [1].

Cholesterol sulfate is a multifunctional endogenous sterol sulfate and selective DOCK2 inhibitor with an IC50 of 2 μM in mouse assays. Cholesterol sulfate plays multiple roles including in epidermal barrier formation by regulating keratinocyte differentiation and corneocyte desquamation, functions as a serine-protease inhibitor, acts as a glucocorticoid receptor antagonist, and activates RORα/γ in the thymus. Cholesterol sulfate serves as a critical research tool for investigating cutaneous biology, immunomodulation, steroid metabolism, sperm capacitation, platelet aggregation, and disorders such as X-linked ichthyosis.