JI-101 is an orally bioactive multi-kinase inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor beta (PDGFRb), and the ephrin B4 receptor B4 (EphB4) with potential antiangiogenic and antineoplastic activities. JI-101 has shown potent in vitro and in vivo anticancer activity against a variety of cancer cell lines and xenografts. It is currently entering Phase II clinical development for the treatment of solid tumors. JI-101 is found to be stable in all preclinical and human liver microsomes. The % metabolized is ranged between 3.03-3.95 across the tested species liver microsomes.The % metabolized is relatively higher in mice liver microsomes followed by dog, human and rat liver microsomes.
理化性质和储存条件
| Molecular Weight (MW) | 466.33 |
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| Formula | C22H20BrN5O2 |
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| CAS No. | 900573-88-8 |
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| Storage | -20℃ for 3 years in powder form |
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| -80℃ for 2 years in solvent |
| Solubility (In vitro) | DMSO: 10 mM |
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| Water: <1 mg/mL |
| Ethanol: <1 mg/mL |
| SMILES | O=C(NC1=CC(Br)=CC=C1OC)NC2=CC=CC3=C2C=CN3CC4=CC(N)=NC=C4 |
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| Synonyms | JI101, JI 101, JI-101 |
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实验参考方法
| In Vitro | In vitro activity: JI-101 is an orally bioactive multi-kinase inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor beta (PDGFRb), and the ephrin B4 receptor B4 (EphB4) with potential antiangiogenic and antineoplastic activities. JI-101 is found to be stable in all preclinical and human liver microsomes. The % metabolized is ranged between 3.03-3.95 across the tested species liver microsomes.The % metabolized is relatively higher in mice liver microsomes followed by dog, human and rat liver microsomes. JI-101 is found to be stable in all preclinical and human liver microsomes. The % metabolized is ranged between 3.03-3.95 across the tested species liver microsomes. The % metabolized is relatively higher in mice liver microsomes followed by dog, human and rat liver microsomes
Kinase Assay: JI-101 is an orally bioactive multi-kinase inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor beta (PDGFRb), and the ephrin B4 receptor B4 (EphB4) with potential antiangiogenic and antineoplastic activities.
Cell Assay: JI-101 is found to be stable in all preclinical and human liver microsomes. The % metabolized is ranged between 3.03-3.95 across the tested species liver microsomes. The % metabolized is relatively higher in mice liver microsomes followed by dog, human and rat liver microsomes. |
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| In Vivo | JI-101 is excreted through bile along with its mono- and di-hydroxy metabolites. Following oral administration, JI-101 is rapidly absorbed, reaching Cmax within 2 h. The t1/2 of JI-101 with intravenous and oral route is found to be 1.75±0.79 and 2.66±0.13 h, respectively. The Cl and Vd by intravenous route for JI-101 are found to be 13.0±2.62 mL/min/kg and 2.11±1.42 L/kg, respectively. The tissue distribution of JI-101 is extensive with rapid and preferred uptake into lung tissue. Overall, the oral bioavailability of JI-101 is 55% and the primary route of elimination for JI-101 is feces |
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| Animal model | Rats PK study |
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| Formulation & Dosage | 3 and 30 mg/kg for i. v. (via tail vein) and oral dose (by gavage) |
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| References | Arzneimittelforschung. 2012 Jan;62(1):27-34 |
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