JI051 is a stabilizer for the Hes1-PHB2 interaction. JI051 interacts with a cancer-associated protein chaperone prohibitin 2 (PHB2), induces cell-cycle arrest by inhibiting the Notch downstream effector gene Hes1. Anti-cancer activity[1].
体外研究 (In Vitro)
JI051 causes G2/M cell-cycle arrest[1]. JI051 (0.1-10 µM, 24 hours) significantly inhibits cell proliferation of HEK293 cells, with an EC50 of 0.3 μM[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Proliferation Assay[1]
Cell Line:
HEK293 cells
Concentration:
0.1-10 µM
Incubation Time:
24 hours
Result:
Dose-dependently inhibits the proliferation of HEK293 cells at low concentrations.
分子量
364.44
Formula
C22H24N2O3
CAS 号
2234281-75-3
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Perron A, et al. Small-molecule screening yields a compound that inhibits the cancer-associated transcription factor Hes1 via the PHB2 chaperone. J Biol Chem. 2018 May 25;293(21):8285-8294.
JI-101 is an orally available multi-kinase inhibitor of VEGFR2, PDGFRβ and EphB4 with potent anti-cancer activity.
IC50 & Target[1]
VEGFR2
PDGFRβ
体外研究 (In Vitro)
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[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
JI-101excreted 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[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
466.33
Formula
C22H20BrN5O2
CAS 号
900573-88-8
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Gurav SD, et al. Pharmacokinetics, tissue distribution and identification of putative metabolites of JI-101 – a novel triple kinase inhibitor in rats. Arzneimittelforschung. 2012 Jan;62(1):27-34.
Animal Administration [1]
Rats: Pharmacokinetics and bioavailability assessment of JI-101 are evaluated in a preliminary parallel-group study in male S.D. rats. Four rats (195–210 g) per route receive JI-101 at a dose of 3 and 30 mg/kg for i. v. (via tail vein) and oral dose (by gavage), respectively. Serial blood samples (100 μL) are collected from retro-orbital plexus at pre-dose, 0.12 ( i. v. only) 0.25, 0.5, 1, 2, 4, 8, 10 (oral only) and 24 h. Blood samples are collected in tubes containing K2 EDTA as the anticoagulant and centrifuged for 5 min maintained at 4 °C for plasma separation and stored frozen at −80±10 °C until analysis[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Gurav SD, et al. Pharmacokinetics, tissue distribution and identification of putative metabolites of JI-101 – a novel triple kinase inhibitor in rats. Arzneimittelforschung. 2012 Jan;62(1):27-34.
