Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C18H18N2O3 |
| Molecular Weight | 310.3471 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 1 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC1=C(CCC(O)=O)C(C)=C(N1)\C=C2/C(=O)NC3=C2C=CC=C3
InChI
InChIKey=NHFDRBXTEDBWCZ-ZROIWOOFSA-N
InChI=1S/C18H18N2O3/c1-10-12(7-8-17(21)22)11(2)19-16(10)9-14-13-5-3-4-6-15(13)20-18(14)23/h3-6,9,19H,7-8H2,1-2H3,(H,20,23)(H,21,22)/b14-9-
Orantinib (SU-6668) is an orally bioavailable receptor tyrosine kinase inhibitor. Orantinib binds to and inhibits the autophosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR), thereby inhibiting angiogenesis and cell proliferation. Orantinib also inhibits the phosphorylation of the stem cell factor receptor tyrosine kinase c-kit, often expressed in acute myelogenous leukemia cells. Orantinib was in phase II clinical trials for the treatment of breast cancer. It was also in phase III clinical trials for the treatment of hepatocellular carcinoma. However, this research was terminated in 2014. The compound was originally developed by Sugen (subsidiary of Pfizer). In 1998, a co-development agreement took place between Sugen and Taiho for the compound.
Originator
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| Design, synthesis, and evaluations of substituted 3-[(3- or 4-carboxyethylpyrrol-2-yl)methylidenyl]indolin-2-ones as inhibitors of VEGF, FGF, and PDGF receptor tyrosine kinases. | 1999 Dec 16 |
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| In vivo assessment of antiangiogenic activity of SU6668 in an experimental colon carcinoma model. | 2004 Jan 15 |
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| Combined antiangiogenic and immune therapy of prostate cancer. | 2005 |
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| Combined inhibition of vascular endothelial growth factor and platelet-derived growth factor signaling: effects on the angiogenesis, microcirculation, and growth of orthotopic malignant gliomas. | 2005 Feb |
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| Vascular endothelial growth factor: a therapeutic target for tumors of the Ewing's sarcoma family. | 2005 Mar 15 |
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| Inhibition of peritoneal dissemination of ovarian cancer by tyrosine kinase receptor inhibitor SU6668 (TSU-68). | 2005 Mar 20 |
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| Dose-finding study of the multitargeted tyrosine kinase inhibitor SU6668 in patients with advanced malignancies. | 2005 Sep 1 |
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| Potent platelet-derived growth factor-beta receptor (PDGF-betaR) inhibitors: Synthesis and structure-activity relationships of 7-[3-(cyclohexylmethyl)ureido]-3-{1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl}quinoxalin-2(1H)-one derivatives. | 2007 Feb |
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| 5-Substituted pyrido[2,3-d]pyrimidine, an inhibitor against three receptor tyrosine kinases. | 2009 Feb 1 |
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| Acenaphtho[1,2-b]pyrrole-based selective fibroblast growth factor receptors 1 (FGFR1) inhibitors: design, synthesis, and biological activity. | 2011 Jun 9 |
Patents
Sample Use Guides
Orantinib at 200 mg, twice per day, or placebo was given orally until TACE failure or unacceptable toxicity.
Route of Administration:
Oral
Orantinib (SU-6668) inhibited PDGF-stimulated PDGFRb tyrosine phosphorylation in NIH-3T3 cells overexpressing PDGFRb at a minimum concentration of 0.03–0.1 uM. SU-6668 inhibited acidic FGF-induced
phosphorylation of the FGFR1 substrate 2 (FRS-2) at concentrations
of 10 uM and higher. However, SU-6668 had no detectable
effect on epidermal growth factor-stimulated EGFR tyrosine phosphorylation
in NIH-3T3 cells overexpressing EGFR at concentrations of up to 100 uM. Orantinib (SU-6668) inhibited VEGF-driven mitogenesis of HUVECs in a dose-dependent
manner with a mean IC50 of 0.34 uM.
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C1967
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ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
