WM-1119 (WM1119) is a novel, highly potent, and selective inhibitor of histone acetyltransferase KAT6A/B (lysine acetyltransferase) with potential anticancer activity. It competes with Ac-CoA by binding to the Ac-CoA binding site, and has a high oral bioavailability (F) of 56% in rats. WM-1119 inhibits KAT6A with an IC50 value of of 0.25 μM, and a KD value of 2 nM for KAT6A. WM-1119 induces cell cycle exit and cellular senescence without causing DNA damage. Senescence is INK4A/ARF-dependent and is accompanied by changes in gene expression that are typical of loss of KAT6A function. WM-1119, which has increased bioavailability, arrests the progression of lymphoma in mice.

Physicochemical Properties

Molecular Formula	C18H13F2N3O3S
Molecular Weight	389.37592959404
Exact Mass	389.064
CAS #	2055397-28-7
Related CAS #	2055397-28-7
PubChem CID	133080719
Appearance	Off-white to light yellow solid powder
LogP	2.8
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	5
Heavy Atom Count	27
Complexity	614
Defined Atom Stereocenter Count	0
SMILES	S(C1C=CC=CC=1F)(NNC(C1C=C(C=C(C2C=CC=CN=2)C=1)F)=O)(=O)=O
InChi Key	QLXULUNLCRKWRD-UHFFFAOYSA-N
InChi Code	InChI=1S/C18H13F2N3O3S/c19-14-10-12(16-6-3-4-8-21-16)9-13(11-14)18(24)22-23-27(25,26)17-7-2-1-5-15(17)20/h1-11,23H,(H,22,24)
Chemical Name	3-fluoro-N'-(2-fluorophenyl)sulfonyl-5-pyridin-2-ylbenzohydrazide
Synonyms	WM1119;WM 1119;WM-1119
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	Without causing damage to DNA, WM-1119 triggers cell cycle exit and cellular senescence. Compared to KAT5 or KAT7, WM-1119 is 1,100- and 250-fold more active against KAT6A, respectively. As a result, it exhibits higher specificity for KAT6A than WM-8014. When MEFs are treated with WM-1119, they experience a G1 cell cycle arrest and a senescence phenotype resembling that of WM-8014. WM-1119 exhibits significantly higher activity in this cell-based assay compared to WM-8014, and at 1 μM, it can induce cell cycle arrest. As anticipated based on decreased protein binding, WM-1119 (IC50=0.25 μM) is nine times more potent than WM-8014 (IC50=2.3 μM) in suppressing the growth of EMRK1184 lymphoma cells in vitro[1].
ln Vivo	With the exception of one mouse that does not respond, the cohorts that get WM-1119 four times a day have stopped the growth of their tumors by day 14. The spleen weights of the four times daily treated WM-1119 treatment group are significantly less than those of the vehicle-treated group. While administering WM-1119 three times a day reduces the tumour burden and spleen weight significantly, it is not as effective as administering it four times a day. WM-1119 is well-tolerated in mice; no widespread negative effects are seen, and there is no evidence of weight loss. Four times a day of WM-1119 treatment significantly reduces the proportion and total quantity of tumor cells[1].
Animal Protocol	Mouse tumor models
References	[1]. Inhibitors of histone acetyltransferases KAT6A/B induce senescence and arrest tumour growth. Nature. 2018 Aug;560(7717):253-257.

Solubility Data

Solubility (In Vitro)

DMSO:≥ 150 mg/mL (385 mM) Water: NA Ethanol: NA

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.42 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 2: ≥ 2.08 mg/mL (5.34 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 3: ≥ 2.08 mg/mL (5.34 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	2.5682 mL	12.8409 mL	25.6819 mL
	5 mM	0.5136 mL	2.5682 mL	5.1364 mL
	10 mM	0.2568 mL	1.2841 mL	2.5682 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.