YK-4-279 (YK-4279; YK4279; YK4-279; YK 4-279) is a potent inhibitor of EWS-FLI1 binding to RNA helicase A (RHA) with potential anticancer activity. It blocks the interactions between RHA and ES-FLI1 proteins. In a transgenic mouse model, YK-4-279 effectively counteracts the leukemia caused by EWS-FLI1. Targeting the oncogene EWS-FLI1, YK-4-279 exhibits specificity. By preventing EWS-FLI1 from interacting with RHA in TC32 cells that have EWS-FLI1 present, YK-4-279 reduces the amount of cyclin D. Additionally, YK-4-279 induces apoptosis and selectively inhibits the growth of ESFT cells. Additionally, YK-4-279 reduces cell motility and invasion by blocking the biological activity of ERG and ETV1 in fusion-positive prostate cancer cells.

Physicochemical Properties

Molecular Formula	C17H13CL2NO4
Molecular Weight	366.20
Exact Mass	365.022
Elemental Analysis	C, 55.76; H, 3.58; Cl, 19.36; N, 3.83; O, 17.48
CAS #	1037184-44-3
Related CAS #	1037184-44-3
PubChem CID	44632017
Appearance	White solid powder
Density	1.5±0.1 g/cm3
Boiling Point	608.9±55.0 °C at 760 mmHg
Melting Point	149-151℃
Flash Point	322.1±31.5 °C
Vapour Pressure	0.0±1.8 mmHg at 25°C
Index of Refraction	1.631
LogP	3.03
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	4
Heavy Atom Count	24
Complexity	509
Defined Atom Stereocenter Count	0
SMILES	ClC1C([H])=C([H])C(=C2C=1C(C(N2[H])=O)(C([H])([H])C(C1C([H])=C([H])C(=C([H])C=1[H])OC([H])([H])[H])=O)O[H])Cl
InChi Key	HLXSCTYHLQHQDJ-UHFFFAOYSA-N
InChi Code	InChI=1S/C17H13Cl2NO4/c1-24-10-4-2-9(3-5-10)13(21)8-17(23)14-11(18)6-7-12(19)15(14)20-16(17)22/h2-7,23H,8H2,1H3,(H,20,22)
Chemical Name	4,7-dichloro-3-hydroxy-3-[2-(4-methoxyphenyl)-2-oxoethyl]-1H-indol-2-one
Synonyms	YK-4-279; YK-4279; YK4279; YK4-279; YK 4-279; YK 4279
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	TC32 ( IC50 = 0.94 µM ); TC71 ( IC50 = 1.83 µM ); RDES ( IC50 = 1.03 µM ); SKES ( IC50 = 0.33 µM ); MMH-ES-1 ( IC50 = 0.94 µM ); STA-ET 7.2 ( IC50 = 0.60 µM ); A4573 ( IC50 = 1.46 µM ); PC3 ( IC50 = 4.95 µM ); MCF7 ( IC50 = 22.82 µM ); MDA-MB-231 ( IC50 = 0.82 µM ); PANC1 ( IC50 = 1.514 µM ); ASPC1 ( IC50 = 14.28 µM )
ln Vitro	YK-4-279 reduces the amount of cyclin D by preventing EWS-FLI1 from interacting with RHA in TC32 cells that have EWS-FLI1. Additionally, YK-4-279 specifically causes apoptosis and suppresses the growth of ESFT cells.[1] In fusion-positive prostate cancer cells, YK-4-279 also suppresses the biological activity of ERG and ETV1, which further reduces cell invasion and motility.[2]
ln Vivo	YK-4-279 (1.5 mg/dose i.p.) inhibits ESFT xenograft tumor growth in vivo.[1] YK-4-279 specifically inhibits the growth and metastasis of prostate cancer in fusion-positive LNCaP-luc-M6 tumors in a mouse model.[3]
Cell Assay	Cell Line: TC32, ES925, GUES1, TC71, A673, A4573, CHP100, PANC1, ASP1, MCF-7, MDA-MB-231, PC-3, HFK and HEC cell lines Concentration: 3-30 µM Incubation Time: 72 h Result: Inhibited cell growth with IC50s of 900 nM, 1 μM and 8 μM for TC32, ES925 and GUES1 cells, respectively.
Animal Protocol	Dissolved in DMSO; 1.5 mg/dose; i.p. injection Nude mice bearing prostate cancer PC3, TC71 or CHP-100 xenografts
References	[1]. Nat Med . 2009 Jul;15(7):750-6. [2]. PLoS One . 2011 Apr 29;6(4):e19343. [3]. PLoS One . 2014 Dec 5;9(12):e114260.
Additional Infomation	4,7-dichloro-3-hydroxy-3-[2-(4-methoxyphenyl)-2-oxoethyl]-1H-indol-2-one is an aromatic ketone.

Solubility Data

Solubility (In Vitro)

DMSO: 25~73 mg/mL (68.3~199.3 mM) Water:<1 mg/mL Ethanol:51 mg/mL (139.3 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.83 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 (6.83 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 (6.83 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	2.7307 mL	13.6537 mL	27.3075 mL
	5 mM	0.5461 mL	2.7307 mL	5.4615 mL
	10 mM	0.2731 mL	1.3654 mL	2.7307 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.