GSK9311 is an analog of GSK-6853, which is a benzimidazolone analog and a novel potent and highly selective inhibitor of the BRPF1 (Bromodomain and PHD Finger-containing) bromodomain with micromolar activity in a cellular target engagement assay, it shows excellent BRPF1 potency (pKd 9.5) and greater than 1600-fold selectivity over all other bromodomains tested. The BRPF protein family are important scaffolding proteins for assembly of MYST histone acetyltransferase complexes. Screening GSK6853 against a panel of 48 unrelated assays reveals only off-target activities that are relatively weak compared to the BRPF1 potency. However, to minimize the chance of off-target effects , the recommended concentration is no higher than 1 μM in cell-based assays.

Physicochemical Properties

Molecular Formula	C24H31N5O3
Molecular Weight	437.534645318985
Exact Mass	437.242
CAS #	1923851-49-3
Related CAS #	GSK9311 hydrochloride;2253733-09-2
PubChem CID	121232406
Appearance	White to off-white solid powder
LogP	2.2
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	5
Heavy Atom Count	32
Complexity	691
Defined Atom Stereocenter Count	1
SMILES	C[C@@H]1CNCCN1C2=C(N(CC)C(C3=CC=CC=C3OC)=O)C=C(C(N4C)=C2)N(C)C4=O
InChi Key	WFXIHQFRQPGCCR-MRXNPFEDSA-N
InChi Code	InChI=1S/C24H31N5O3/c1-6-28(23(30)17-9-7-8-10-22(17)32-5)20-13-18-19(27(4)24(31)26(18)3)14-21(20)29-12-11-25-15-16(29)2/h7-10,13-14,16,25H,6,11-12,15H2,1-5H3/t16-/m1/s1
Chemical Name	N-[1,3-dimethyl-6-[(2R)-2-methylpiperazin-1-yl]-2-oxobenzimidazol-5-yl]-N-ethyl-2-methoxybenzamide
Synonyms	GSK9311; GSK-9311; GSK 9311
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	GSK6853 exhibits characteristics appropriate for cellular and in vivo investigations. It is a highly selective, soluble, cell active (20 nM), and potent (300 pM) inhibitor of the BRPF1 bromodomain. GSK6853 is an analogue of GSK6853 that is less active and has an alkylated 5-amide[1].
ln Vivo	In male CD1 mouse, following IV administration (1 mg/kg), GSK6853 demonstrates a high blood clearance of 107 mL/min/kg, a moderate volume of distribution (5.5 L/kg) and a moderate terminal half-life of 1.7 h. Oral administration (PO, 3 mg/kg) achieves a moderate systemic exposure, with a Cmax of 42 ng/mL and Tmax of 1.5 h, resulting in a bioavailability of 22%. The intraperitoneal route of administration (IP, 3 mg/kg) reaches a Cmax of 469 ng/mL and Tmax of 0.25 h, resulting in a bioavailability of 85%. The results indicate that the IP route of administration would be suitable for dosing this molecule in potential PKPD models.
Animal Protocol	1 mg/kg; i.p. or i.v. injection CD1 mice
References	[1]. GSK6853, a Chemical Probe for Inhibition of the BRPF1 Bromodomain. ACS Med Chem Lett. 2016 May 9;7(6):552-7.

Solubility Data

Solubility (In Vitro)

DMSO: 10 mM Water:<1 mg/mL Ethanol:<1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.71 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 (5.71 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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 (5.71 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 25.0 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	2.2856 mL	11.4278 mL	22.8556 mL
	5 mM	0.4571 mL	2.2856 mL	4.5711 mL
	10 mM	0.2286 mL	1.1428 mL	2.2856 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.