WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 201611
Description: JI-101 is an orally active 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. Angiogenesis inhibitor JI-101 binds to and inhibits VEGFR2, PDGFRb and EphB4, which may inhibit tumor angiogenesis and, so, cellular proliferation in tumor cells overexpressing VEGFR2, PDGFRb and EphB4. The receptor tyrosine kinases VEGFR2, PDGFRb and EphB4 may be overexpressed in a number of different cancer cell types and may play crucial roles in tumor angiogenesis.
MedKoo Cat#: 201611
Chemical Formula: C22H20BrN5O2
Exact Mass: 465.08
Molecular Weight: 466.339
Elemental Analysis: C, 56.66; H, 4.32; Br, 17.13; N, 15.02; O, 6.86
Synonym: JI101, JI 101, JI-101
IUPAC/Chemical Name: 1-(1-((2-aminopyridin-4-yl)methyl)-1H-indol-4-yl)-3-(5-bromo-2-methoxyphenyl)urea.
InChi Key: ZXBFYBLSJMEBEP-UHFFFAOYSA-N
InChi Code: InChI=1S/C22H20BrN5O2/c1-30-20-6-5-15(23)12-18(20)27-22(29)26-17-3-2-4-19-16(17)8-10-28(19)13-14-7-9-25-21(24)11-14/h2-12H,13H2,1H3,(H2,24,25)(H2,26,27,29)
SMILES Code: O=C(NC1=CC(Br)=CC=C1OC)NC2=CC=CC3=C2C=CN3CC4=CC(N)=NC=C4
Appearance: Solid powder
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
|Biological target:||JI-101 is an orally available multi-kinase inhibitor of VEGFR2, PDGFRβ and EphB4 with potent anti-cancer activity.|
|In vitro activity:||The treatment with 10 µM of JI‐101 also decreased the proliferation rate of EPHB4 mutant clone compared to vehicle (DMSO) in SHSY5Y cells, and also of EPHB4‐WT compared to vehicle (Figure 6B) at 72 hours. Reference: J Cell Mol Med. 2020 Jun;24(11):6459-6471. https://pubmed.ncbi.nlm.nih.gov/32336043/|
|In vivo activity:||TBD|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
The following data is based on the product molecular weight 466.339 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.15 mL||5.76 mL||11.51 mL|
|5 mM||0.23 mL||1.15 mL||2.3 mL|
|10 mM||0.12 mL||0.58 mL||1.15 mL|
|50 mM||0.02 mL||0.12 mL||0.23 mL|
|Formulation protocol:||1. Andolfo I, Lasorsa VA, Manna F, Rosato BE, Formicola D, Iolascon A, Capasso M. Kinome multigenic panel identified novel druggable EPHB4-V871I somatic variant in high-risk neuroblastoma. J Cell Mol Med. 2020 Jun;24(11):6459-6471. doi: 10.1111/jcmm.15297. Epub 2020 Apr 26. PMID: 32336043; PMCID: PMC7294133.|
|In vitro protocol:||1. Andolfo I, Lasorsa VA, Manna F, Rosato BE, Formicola D, Iolascon A, Capasso M. Kinome multigenic panel identified novel druggable EPHB4-V871I somatic variant in high-risk neuroblastoma. J Cell Mol Med. 2020 Jun;24(11):6459-6471. doi: 10.1111/jcmm.15297. Epub 2020 Apr 26. PMID: 32336043; PMCID: PMC7294133.|
|In vivo protocol:||TBD|
1: Gurav SD, Gilibili RR, Jeniffer S, Mohd Z, Giri S, Govindarajan R, Srinivas NR, Mullangi R. 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. Epub 2012 Jan 10. PubMed PMID: 22331760.
2: Gurav SD, Jeniffer S, Punde R, Gilibili RR, Giri S, Srinivas NR, Mullangi R. A strategy for extending the applicability of a validated plasma calibration curve to quantitative measurements in multiple tissue homogenate samples: a case study from a rat tissue distribution study of JI-101, a triple kinase inhibitor. Biomed Chromatogr. 2012 Apr;26(4):419-24. doi: 10.1002/bmc.1680. Epub 2011 Aug 23. PubMed PMID: 21877323.
3: Sharma S, Dubey NK, Dasgupta AK, Sahu M, Benjamin B, Mullangi R, Srinivas NR. Highly sensitive method for the determination of JI-101, a multi-kinase inhibitor in human plasma and urine by LC-MS/MS-ESI: method validation and application to a clinical pharmacokinetic study. Biomed Chromatogr. 2012 Feb;26(2):232-8. doi: 10.1002/bmc.1652. Epub 2011 May 19. PubMed PMID: 21594880.
4: Gurav SD, Gilibili RR, Jeniffer S, Giri S, Srinivas NR, Mullangi R. Highly sensitive method for the determination of a novel triple kinase inhibitor with anti-cancer activity, JI-101, in rat plasma by liquid chromatography-electrospray ionization tandem mass spectrometry: application to a pharmacokinetic study. Biomed Chromatogr. 2011 Jul;25(7):794-800. doi: 10.1002/bmc.1518. Epub 2010 Sep 27. PubMed PMID: 20872957.
(Last updated: 4/20/2016).
JI-101 is a novel orally active kinase inhibitor, which 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. Overall, the oral bioavailability of JI-101 is 55% and the primary route of elimination for JI-101 is feces. (source: Arzneimittelforschung. 2012 Jan;62(1):27-34. Epub 2012 Jan 10.)