215543-92-3 Usage
Description
SU5402, also known as 3-(2-carboxyethyl)-4-methyl-1H-pyrrol-2-yl-3-methyleneoxindole, is a potent and specific inhibitor of fibroblast growth factor receptor (FGFR). It is an ATP-competitive inhibitor that targets the tyrosine kinase activity of FGFR1, playing a crucial role in various cellular processes. SU5402 is a yellow-green solid and has been widely studied for its potential applications in the field of cancer research and treatment.
Uses
Used in Cancer Research and Treatment:
SU5402 is used as a specific FGFR inhibitor for studying the role of FGFR in cancer cell signaling and proliferation. It has been shown to inhibit FGFR phosphorylation in vitro, in cell culture, and in mouse tumor cell models, making it a valuable tool in understanding the underlying mechanisms of cancer development and progression.
Used in Cell Signaling Experiments:
SU5402 is used as a fibroblast growth factor receptor inhibitor in cell signaling experiments to stimulate cells for MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. This allows researchers to study the effect of SU5402 on the expression of osteogenic markers and the expression of osteoprotegerin and RANKL (runt-related transcription factor RUNX2).
Used in Drug Development:
SU5402 serves as an intermediate for 3-(hetero)arylmethylidene-2-indolinone derivatives, which are modulators of protein kinase activity. These derivatives are being investigated for their potential use in treating cancer, as they may help modulate the activity of various protein kinases involved in cancer cell growth and survival.
Used in Embryo Co-treatment Studies:
SU5402 is used to co-treat embryos in order to study its effect on osteogenic markers. This application helps researchers understand the role of FGFR in embryonic development and the potential implications of targeting this receptor in the context of developmental disorders or cancer treatment.
Used in Drug Delivery Systems:
While not explicitly mentioned in the provided materials, SU5402's potential applications in drug delivery systems could be explored. As a specific FGFR inhibitor, it may be incorporated into novel drug delivery systems to enhance its bioavailability, targeting, and therapeutic outcomes in cancer treatment.
Biological Activity
Potent and selective vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR) inhibitor (IC 50 values are 0.02, 0.03, 0.51 and > 100 μ M at VEGFR2, FGFR1, PDGFR β and EGFR respectively). Inhibits embryonic left-right determination and exhibits potent anticancer activity in vitro and in vivo .
Biochem/physiol Actions
SU-5402 has inhibitory effect on the action of tyrosine kinases. It competitively binds to the ATP-binding site on the fibroblast growth factor receptor (FGFR).
in vitro
su5402 could inhibit fgfr3 phosphorylation in vitro. b cells dependent on fgfr3 for survival were sensitive to su5402 specifically. a panel of 11 human myeloma cell lines was studied, among which five beared t(4;14) translocation. the kms11 human myeloma cell line expressesing constitutively active mutant fgfr3, displayed a 95% increase in g0/g1 cells as well as 45-fold increase in apoptotic cells after su5402 treatment. in addition, the activated signal-regulated kinases 1 and 2 and signal activator of transcription 3 were down-regulated after su5402 treatment rapidly. in human myeloma cell lines with wild-type fgfr3, the stimulating effect of afgf ligand was abrogated by su5402 [1].
in vivo
balb/c mice were inoculated with syngeneic pre-b-td cells and these established tumours were treated with 300 ng/kg su5402 or carrier alone administered by either direct subcutaneous or intraperitoneal injection. tumours were collected 24 h later and western blot analyses indicated a treatment-related decrease in the levels of activated erk1/2 in the harvested tumors [1].
IC 50
0.02, 0.03, 0.51 and > 100 μm for vegfr2, fgfr1, pdgfrβ and egfr, respectively
References
1) Lee et al. (2013), Interleukin-1β enhances cell migration through AP-κ1 and NF-B pathway dependent FGF2 expression in human corneal endothelial cells; Biol. Cell, 105 175
2) Paterson et al. (2004), Preclinical studies of fibroblast growth factor receptor 3 as a therapeutic target in multiple myeloma; Br. J. Haematol., 124 595
3) Jin et al. (2012), Eosinophil cationic protein enhances cardiomyocyte differentiation of P19CL6 embryonal carcinoma cells by stimulating the FGF receptor signaling pathway; Growth Factors, 30 344
Check Digit Verification of cas no
The CAS Registry Mumber 215543-92-3 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,1,5,5,4 and 3 respectively; the second part has 2 digits, 9 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 215543-92:
(8*2)+(7*1)+(6*5)+(5*5)+(4*4)+(3*3)+(2*9)+(1*2)=123
123 % 10 = 3
So 215543-92-3 is a valid CAS Registry Number.
InChI:InChI=1/C17H16N2O3/c1-10-9-18-15(11(10)6-7-16(20)21)8-13-12-4-2-3-5-14(12)19-17(13)22/h2-5,8-9,18H,6-7H2,1H3,(H,19,22)(H,20,21)/b13-8-
