YK-4-279 Property

Melting point:

149-151℃

Boiling point:

608.9±55.0 °C(Predicted)

Density 

1.456

storage temp. 

Store at -20° C.

solubility 

insoluble in H2O; ≥16.35 mg/mL in DMSO; ≥24.25 mg/mL in EtOH with ultrasonic

form 

Powder

pka

10.43±0.20(Predicted)

color 

White to off-white

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P271Use only outdoors or in a well-ventilated area.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P330Rinse mouth.

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P337+P313IF eye irritation persists: Get medical advice/attention.

P362Take off contaminated clothing and wash before reuse.

P403+P233Store in a well-ventilated place. Keep container tightly closed.

P405Store locked up.

P501Dispose of contents/container to..…

YK-4-279 Chemical Properties,Usage,Production

Chemical Properties

A crystalline solid

Uses

YK-4-279 is a small molecule inhibitor of EWS-FLI1 protein, and has been shown to disrupt the mitotic progression of neuroblastoma cells, and potentially other cancers.

Uses

An oncogenic fusion protein found in Ewing's sarcoma, a family of undifferentiated tumors which occur throughout the body. The binding of ES-FLI1 to RNA helicase A (RHA) promotes its oncogenic function. Inhibits protein-protein interactions between ES-FLI1 and RHA. At 10 μM, YK-4-279 blocks RHA binding to ES-FLI1 and induces apoptosis of a panel of Ewing's sarcoma tumor cell lines with IC50 values ranging from 0.5 to 2 μM.1 At 1.5 mg per dose, YK-4-279 reduces the growth of Ewing's sarcoma orthotopic xenografts in mice after treatment with the inhibitor for two weeks.

Definition

ChEBI: 4,7-dichloro-3-hydroxy-3-[2-(4-methoxyphenyl)-2-oxoethyl]-1H-indol-2-one is an aromatic ketone.

Biological Activity

yk 4-279 is an inhibitor of rna helicase a (rha) binding to the oncogenic transciption factor ews-fli1.ews-fli1 is a disordered protein that precludes standard structure-based small-molecule inhibitor design. ews-fli1 binding to rna helicase a (rha) is important for its oncogenic function.

in vitro

esft cells treated with yk-4-279 showed a dissociation of ews-fli1 from rha by 10 mm, consistent with the kd value. the ews-fli1–transfected cells showed a dose-dependent decrease in promoter activity when treated for 18 h with 3 mm and 10 mm yk-4-279. yk-4-279 was relatively specific for esft cells as compared to the nontransformed hek293 cells [1].

in vivo

the tumor growth rate of yk-4-279–treated mice bearing chp-100 was lower than that in mice having pc3 prostate tumors. the cumulative data from five independent experiments with the esft xenografts (tc71 and chp-100) show a marked overall tumor reduction in the yk-4-279–treated mice. pathological analysis of mice treated with yk-4-279 did not show any signs of toxicity, except for sterile inflammatory lesions in the abdominal cavities of mice [1].

storage

Store at +4°C

References

[1] erkizan hv, kong y, merchant m, schlottmann s, barber-rotenberg js, yuan l, abaan od, chou th, dakshanamurthy s, brown ml, uren a, toretsky ja. a small molecule blocking oncogenic protein ews-fli1 interaction with rna helicase a inhibits growth of ewing's sarcoma. nat med. 2009;15(7):750-6.