GSK854 is a novel and potent TNNI3K (Troponin I-Interacting Kinase) inhibitor with IC50 (TNNI3K) < 10 nM. GSK854 exhibits substantial selectivity against B-Raf (>25-fold) and EGFR (IC50 > 25 μM), excellent broad spectrum kinase selectivity with >100-fold selectivity over 96% of kinases tested (≤50% inhibition @ 1 μM for 282 of 294 kinases, high activity in a TNNI3K cellular assay (IC50 = 8 nM), good pharmacokinetics in rats (Cl = 14 mL/min/kg, Vdss = 1.9 L/kg, t1/2 = 2.3 h, F = 48%).

Physicochemical Properties

Molecular Formula	C18H19CLN6O4S2
Molecular Weight	482.964259386063
Exact Mass	482.0598
CAS #	1316059-00-3
Related CAS #	1316059-00-3;
PubChem CID	68304261
Appearance	Off-white to light yellow solid powder
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	8
Heavy Atom Count	31
Complexity	788
Defined Atom Stereocenter Count	0
SMILES	ClC1=CN=C(C=C1)NC1=CC(=NC=N1)NC1C=C(C=CC=1S(CC)(=O)=O)S(NC)(=O)=O
InChi Key	OEDGERSSZUMLBI-UHFFFAOYSA-N
InChi Code	InChI=1S/C18H19ClN6O4S2/c1-3-30(26,27)15-6-5-13(31(28,29)20-2)8-14(15)24-17-9-18(23-11-22-17)25-16-7-4-12(19)10-21-16/h4-11,20H,3H2,1-2H3,(H2,21,22,23,24,25)
Chemical Name	3-[6-(5-Chloro-pyridin-2-ylamino)-pyrimidin-4-ylamino]-4-ethanesulfonyl-N-methyl-benzenesulfonamide
Synonyms	GSK854 GSK-854 GSK 854.
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

References

[1]. 4,6-Diaminopyrimidines as Highly Preferred Troponin I-Interacting Kinase (TNNI3K) Inhibitors. J Med Chem. 2018;61(7):3076-3088.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~517.64 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.31 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 (4.31 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	2.0706 mL	10.3528 mL	20.7056 mL
	5 mM	0.4141 mL	2.0706 mL	4.1411 mL
	10 mM	0.2071 mL	1.0353 mL	2.0706 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.