GSK2801 (GSK-2801) is a novel, orally bioavailable, selective, cell bioactive and acetyl-lysine competitive inhibitor of BAZ2A and BAZ2B bromodomains, which are the two closely related bromodomain containing proteins BAZ2A and BAZ2B constitute the central scaffolding protein of the nucleolar remodeling complex (NoRC) that regulates the expression of noncoding RNAs. GSK2801 inhibits BAZ2A and BAZ2B with Kd of 257 nM and 136 nM, respectively. It has the potential to be used as a versatile tool compound for cellular and in vivo studies to understand the role of BAZ2 bromodomains in chromatin biology.

Physicochemical Properties

Molecular Formula	C20H21NO4S
Molecular Weight	371.45
Exact Mass	371.119
CAS #	1619994-68-1
Related CAS #	1619994-68-1
PubChem CID	73010930
Appearance	Light yellow to khaki solid powder
Density	1.2±0.1 g/cm3
Index of Refraction	1.596
LogP	2.95
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	6
Heavy Atom Count	26
Complexity	599
Defined Atom Stereocenter Count	0
InChi Key	KHWCPNJRJCNVRI-UHFFFAOYSA-N
InChi Code	InChI=1S/C20H21NO4S/c1-4-11-25-15-9-10-21-18(14(2)22)13-17(19(21)12-15)16-7-5-6-8-20(16)26(3,23)24/h5-10,12-13H,4,11H2,1-3H3
Chemical Name	1-(1-(2-(methylsulfonyl)phenyl)-7-propoxyindolizin-3-yl)ethanone
Synonyms	GSK-2801; GSK 2801; GSK2801
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

ln Vitro	GSK2801 binds TAF1L(2) with an affinity KB of 0.31μM (KD: 3.2 μM) and a binding enthalpy change ΔH of −8.6 kcal/mol. ITC tests employing the bromodomain of BRD9 results in the measurement of an affinity KB of 0.826 μM (KD: 1.1 μM) and ΔH of −9.8 kcal/mol[1]. GSK2801 or RNAi suppression of BAZ2A/B with JQ1 selectively displaced BRD2 to promoters/enhancers of ETS-regulated genes. In 2D cells, enhanced displacement of BRD2 from chromatin by combined pharmacological therapy triggered senescence. In spheroid cultures, combined therapy produces cleaved caspase-3 and cleavage PARP typical of apoptosis in tumor cells. Thus, GSK2801 suppresses BRD2-driven transcription in conjunction with BET inhibitor and promotes apoptosis of TNBC[2] .
ln Vivo	After oral and intraperitoneal dosing to male CD1 mice, the pharmacokinetic characteristics are assessed to assess the appropriateness of GSK2801 for in vivo investigations. Following oral dosage, GSK2801 exhibits a decent in vivo exposure, mild clearance, and reasonable plasma stability[1].
Animal Protocol	Formulated in 0.5% CMC+1% Tween 80; 30 mg/kg; i.p. or p.o. Male CD1 mice
References	[1]. Discovery and Characterization of GSK2801, a Selective Chemical Probe for the Bromodomains BAZ2A and BAZ2B. J Med Chem. 2016 Feb 25;59(4):1410-24. [2]. GSK2801, a BAZ2/BRD9 Bromodomain Inhibitor, Synergizes with BET Inhibitors to Induce Apoptosis in Triple-Negative Breast Cancer. Mol Cancer Res. 2019 Jul;17(7):1503-1518.

Solubility Data

Solubility (In Vitro)

DMSO: 74 mg/mL (199.2 mM) Water:<1 mg/mL Ethanol:7 mg/mL (18.8 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.73 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 25.0 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: 2.5 mg/mL (6.73 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with heating and sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: 2.5 mg/mL (6.73 mM) 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 0.5% CMC+1% Tween 80: 30mg/mL  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.6922 mL	13.4608 mL	26.9215 mL
	5 mM	0.5384 mL	2.6922 mL	5.3843 mL
	10 mM	0.2692 mL	1.3461 mL	2.6922 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.