5-CHLORO-3-[(3,5-DIMETHYLPYRROL-2-YL)METHYLENE]-2-INDOLINONE Property

Boiling point:

508.6±50.0 °C(Predicted)

Density 

1.352±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,2-8°C

solubility 

DMSO: ≥20mg/mL

pka

11.96±0.20(Predicted)

form 

powder

color 

orange

Safety

Risk Statements 

53

WGK Germany 

3

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H413May cause long lasting harmful effects to aquatic life

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

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

P273Avoid release to the environment.

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

P330Rinse mouth.

5-CHLORO-3-[(3,5-DIMETHYLPYRROL-2-YL)METHYLENE]-2-INDOLINONE Chemical Properties,Usage,Production

Uses

SU5614 is a FMS-like tyrosine kinase 3 (FLT3) inhibitor; selective inhibitor of VEGF and PDGF receptor tyrosine kinases.

Definition

ChEBI: SU5614 is a member of the class of oxindoles that is 5-chlorooxindole in which the two hydrogens at position 3 are replaced by a (3,5-dimethylpyrrol-2-yl)methylidene group. It has a role as a vascular endothelial growth factor receptor antagonist. It is a member of pyrroles, a member of oxindoles and an organochlorine compound.

Biological Activity

su5614 is a protein tyrosine kinase inhibitor.tyrosine kinases are enzymes for the activation of many proteins by signal transduction cascades. the proteins are activated by adding a phosphate group to the protein.

in vitro

previous study found that su5614 could induce growth arrest and apoptosis in c-kit-expressing kasumi-1, m-07e, and ut-7 cells and inhibited the stem cell factor (scf)-induced tyrosine phosphorylation of c-kit. moreover, the sensitivity of kasumi-1 cells towards the growth inhibitory activity of su5614 was mainly caused by an autocrine production of scf, but not by the transforming mutations of c-kit [1].

in vivo

it was found that administration of su5614, a vascular endothelial growth factor (vegf) inhibitor, to mice could reduce the levels of vegf dramatically in bal fluids 72 h after toluene diisocyanate inhalation. moreover, consistent with the results obtained from the enzyme immunoassays, western blot analyses showed that su5614 reduced the levels of vegf in the bal fluid 72 h after toluene diisocyanate inhalation. these results suggested that vegf might be one of the major determinants of toluene diisocyanate -induced asthma and that the inhibition of vegf might be a good therapeutic strategy [2].

IC 50

100 nm for flt3 inhibition

References

[1] spiekermann k,faber f,voswinckel r,hiddemann w. the protein tyrosine kinase inhibitor su5614 inhibits vegf-induced endothelial cell sprouting and induces growth arrest and apoptosis by inhibition of c-kit in aml cells. exp hematol.2002 jul;30(7):767-73.
[2] lee yc,kwak yg,song ch. contribution of vascular endothelial growth factor to airway hyperresponsiveness and inflammation in a murine model of toluene diisocyanate-induced asthma. j immunol.2002 apr 1;168(7):3595-600.