GSK761 is a selective inhibitor of Sp 140 nuclear body protein (SP140) with IC50 of 77.79 nM. GSK761 reduces monocyte differentiation into inflammatory macrophages and lipopolysaccharide (LPS)-induced inflammatory activation. GSK761 induced the generation of CD206+ regulatory macrophages by inhibiting SP140.

Physicochemical Properties

Molecular Formula	C40H46N4O4
Molecular Weight	646.82
Appearance	White to off-white solid powder
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	IC50: 77.79 nM (Speckled 140 kDa, SP140)[1]
ln Vitro	In HuT78 cells and HEK293 cells transfected with halo-tag SP140, GSK761 binds to SP140 [1]. In M1 polarized macrophages, GSK761 (0.01-1.11 µM; 1 h) decreases inflammatory activation and downregulates the expression of pro-inflammatory cytokines such as TNF, IL-6, IL-12p70, IL-1β, IL-8, and IL-10[1]. In CD14+ mucosal macrophages, GSK761 (0.04 µM; 4 h) dramatically lowers the expression of TNF, IL6, and IL10 [1].
References	[1]. Modulation of macrophage inflammatory function through selective inhibition of the epigenetic reader protein SP140. BMC Biol. 2022 Aug 19;20(1):182.

Solubility Data

Solubility (In Vitro)

DMSO :~125 mg/mL (~193.25 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (3.22 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.22 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.5460 mL	7.7301 mL	15.4603 mL
	5 mM	0.3092 mL	1.5460 mL	3.0921 mL
	10 mM	0.1546 mL	0.7730 mL	1.5460 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.