286370-15-8 Usage
Description
KRN 633 is an ATP-competitive inhibitor that targets vascular endothelial growth factor receptor tyrosine kinase (VEGFR) and platelet-derived growth factor receptor (PDGFR). It is characterized by its ability to inhibit VEGFR1/2/3 with IC50 values of 170 nM, 160 nM, and 125 nM, respectively, and PDGFRα/β with IC50 values of 965 nM and 9850 nM.
Uses
Used in Pharmaceutical Industry:
KRN 633 is used as an antitumor and antiangiogenic agent for its ability to suppress VEGF-dependent activation of MAPK and cell proliferation. It demonstrates efficacy in inhibiting vessel formation and vascular permeability in human tumor xenograft models, making it a promising candidate for cancer treatment.
Used in Cancer Research:
KRN 633 is used as a research tool for studying the role of VEGFR and PDGFR in cancer cell growth and angiogenesis. Its ATP-competitive inhibition of these receptors provides valuable insights into the development of targeted cancer therapies.
Used in Drug Development:
KRN 633 serves as a lead compound in the development of novel small molecule inhibitors targeting VEGFR and PDGFR. Its potent inhibition of these receptors highlights its potential in the creation of new therapeutic agents for cancer treatment.
Biological Activity
krn 633 is a selective inhibitor of vegfr-1, vegfr-2 and vegfr-3 with ic50 value of 170 nm, 160 nm and 125 nm [1].vascular endothelial growth factor receptor (vegfr) is a protein and plays an important role in tumor angiogenesis by cooperating with its ligand vegf [1].krn 633 is a potent vegfr inhibitor. when tested with huvecs, krn 633 inhibited the cell proliferation that mediated by vegf with the ic50 value of 14.9 nmol/l and suppressed the capillary tube formation by ~50% at the dose of 10 nmol/l [1].in mid-pregnant mice model, krn633 was used at the dose of 5 mg/kg once daily from embryonic day 13.5 until the day of delivery and the effect on vascular growth was slightly delayed on postnatal day 4 (p4) and on p8 it was observed that krn633 resulted in the decreased numbers of central arteries and veins and abnormal branching of the central arteries [2]. when tested with athymic mouse xenograft ht29 cells model, administration of krn633 inhibited tumor growth as ~90% from the initial tumor volume rangs from 500-667 mm3, while had less effect du145 xenograft mouse models by inhibiting tumor angiogenesis and vascular permeability [1].
Biochem/physiol Actions
KRN633 is a cell-permeable; reversible and ATP-competitive inhibitor of vascular endothelial growth factor receptor tyrosine kinase (VEGFR) with IC50 values of 170, 160, and 125 nM for VEGFR-1, -2, -3, respectively. Krn633 inhibits PDGFR-α and c-Kit only at higher concentrations (IC50 = 0.97 and 4.33 μM, respectively) and is inactive towards a panel of 17 other kinases (IC50 >/= 10 μM).
references
[1]. nakamura, k., et al., krn633: a selective inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinase that suppresses tumor angiogenesis and growth. mol cancer ther, 2004. 3(12): p. 1639-49.[2]. morita, a., et al., treatment of mid-pregnant mice with krn633, an inhibitor of vascular endothelial growth factor receptor tyrosine kinase, induces abnormal retinal vascular patterning in their newborn pups. birth defects res b dev reprod toxicol, 2014. 101(4): p. 293-9.
Check Digit Verification of cas no
The CAS Registry Mumber 286370-15-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,8,6,3,7 and 0 respectively; the second part has 2 digits, 1 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 286370-15:
(8*2)+(7*8)+(6*6)+(5*3)+(4*7)+(3*0)+(2*1)+(1*5)=158
158 % 10 = 8
So 286370-15-8 is a valid CAS Registry Number.
286370-15-8Relevant articles and documents
QUINOLINE DERIVATIVES AND QUINAZOLINE DERIVATIVES
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, (2008/06/13)
An object of the present invention is to provide compounds which have antitumor activity and do not change cytomorphosis. Disclosed are compounds represented by formula (I) and a pharmaceutically acceptable salts and solvates thereof and pharmaceutical compositions comprising said compounds: wherein X and Z each independently represent CH or N; R1 to R3 represent H, substituted alkoxy, unsubstituted alkoxy or the like; R4 represents H; R5 to R8 represent H, halogen, alkyl, alkoxy, alkylthio, nitro, or amino, provided that R5 to R8 do not simultaneously represent H; R9 and R10 represent H, alkyl, or alkylcarbonyl; and R11 represents alkyl, alkenyl, alkynyl, or aralkyl.
