GSK699

GSK699 is a KAT2A/B/PCAF/GCN5 PROTAC degrader. GSK699 induces proteasome-dependent degradation of KAT2A, KAT2B, PCAF and GCN5, regulates the histone acetyltransferase activity of the SAGA complex, and reduces the level of histone H3K9ac. GSK699 inhibits the growth of neuroblastoma, acute myeloid leukemia and small cell lung cancer cells. GSK699 reduces the production of inflammatory cytokines and chemokines, and impairs LPS-stimulated immune cell responses. GSK699 is applicable to research related to acute myeloid leukemia, small cell lung cancer, neuroblastoma and inflammatory diseases^[1]. In Vitro:GSK699 potently degrades KAT2A (DC₅₀ = 2.2 nM) and KAT2B (DC₅₀ = 0.08 nM) in MOLM-13 cells, and inhibits the proliferation of MOLM-13 cells with an activity of GI₅₀ = 64 nM^[1].
GSK699 potently degrades KAT2A (DC₅₀ = 1.5 nM) and KAT2B (DC₅₀ = 0.1 nM) in NCI-H1048 cells, and inhibits the proliferation of NCI-H1048 cells with a GI₅₀ of 32 nM^[1].
GSK699 inhibits the proliferation of KELLY neuroblastoma cells in vitro^[1].
Treatment of wild-type primary mouse HSPCs with GSK699 (100 nM; 48 h) significantly reduces intracellular H₃K₉ac levels, upregulates cell surface Sca-1 expression, and increases the frequency of immunophenotypic HSCs and megakaryocyte progenitor cells^[2].
Treatment of c-Kit⁺ Sca-1⁺Lin⁻ wild-type primary mouse hematopoietic stem and progenitor cells (HSPCs) with GSK699 (100 nM; 48 h) induces transcriptomic changes that are highly correlated with those caused by Tada2b knockout in HSPCs^[2].
GSK699 (0.03-1000 nM; 18 h) potently induces concentration-dependent degradation of PCAF in THP1 cells^[3].
GSK699 (100 nM; 5-6 days) potently reduces the production of IL-6, IL-12p70, IL-10, IL-1β, IFN-γ, TNF and IL-8 in human monocyte-derived dendritic cells stimulated with LPS (HY-D1056)^[3].
GSK699 (100 nM; 6 days) reduces the production of multiple inflammatory mediators in LPS-stimulated human monocyte-derived dendritic cells, including IL-6, CXCL12, IL12A, TNF, IL-12p70, IL10, CXCL1/GROα, CXCL11/I-TAC, CCL16, CCL7, CCL20/MIP-3α, CXCL10, CXCL1, CCL8 and CCL19/MIP-3β, and upregulates CD1C, FCER1A, CD28 and CD8A^[3].