WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 406351
CAS#: 228559-41-9
Description: Ki8751 is a potent, selective inhibitor of VEGFR-2 tyrosine kinase (IC50 = 0.9 nM). Displays some inhibitory activity towards c-Kit, PDGFR α and FGFR-2 (IC50 values range from 40 to 170 nM).
MedKoo Cat#: 406351
Name: Ki8751
CAS#: 228559-41-9
Chemical Formula: C24H18F3N3O4
Exact Mass: 469.1249
Molecular Weight: 469.4202
Elemental Analysis: C, 61.41; H, 3.87; F, 12.14; N, 8.95; O, 13.63
Synonym: Ki8751; Ki-8751; Ki 8751
IUPAC/Chemical Name: 1-(2,4-difluorophenyl)-3-(4-((6,7-dimethoxyquinolin-4-yl)oxy)-2-fluorophenyl)urea
InChi Key: LFKQSJNCVRGFCC-UHFFFAOYSA-N
InChi Code: InChI=1S/C24H18F3N3O4/c1-32-22-11-15-20(12-23(22)33-2)28-8-7-21(15)34-14-4-6-19(17(27)10-14)30-24(31)29-18-5-3-13(25)9-16(18)26/h3-12H,1-2H3,(H2,29,30,31)
SMILES Code: O=C(NC1=CC=C(OC2=CC=NC3=CC(OC)=C(OC)C=C23)C=C1F)NC4=CC=C(F)C=C4F
Appearance: White to off-white solid powder
Purity: >98% (or refer to the Certificate of Analysis)
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: 0 – 4 C for short term (weeks to 1 month) or -20 C for long terms (months to years).
Solubility: Soluble in DMSO, not soluble in water.
Shelf Life: >2 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: 2934.99.03.00
| Biological target: | Ki8751 is a potent VEGFR2 inhibitor with an IC50 of 0.9 nM. |
| In vitro activity: | VEGF blockade by Ki8751 significantly reduced cancer cell proliferation, and enhanced breast cancer cell apoptosis. Mass spectrometric analyses revealed that Ki8751 treatment significantly upregulated the expression of mitochondrial proteins, suggesting the involvement of mitochondrial biogenesis. Reference: Cancer Biol Med. 2021 Feb 15;18(1):139-154. https://pubmed.ncbi.nlm.nih.gov/33628590/ |
| In vivo activity: | 6ab (Ki8751) showed significant antitumor activity against five human tumor xenografts such as GL07 (glioma), St-4 (stomach carcinoma), LC6 (lung carcinoma), DLD-1 (colon carcinoma) and A375 (melanoma) in nude mice and also showed complete tumor growth inhibition with the LC-6 xenograft in nude rats following oral administration once a day for 14 days at 5 mg/kg without any body weight loss. Reference: J Med Chem. 2005 Mar 10;48(5):1359-66. |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 25.0 | 53.26 | |
| DMF:PBS (pH 7.2) (1:3) | 0.25 | 0.53 | |
| DMSO | 51.49 | 109.68 |
The following data is based on the product molecular weight 469.4202 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. Ni H, Guo M, Zhang X, Jiang L, Tan S, Yuan J, Cui H, Min Y, Zhang J, Schlisio S, Ma C, Liao W, Nister M, Chen C, Li S, Li N. VEGFR2 inhibition hampers breast cancer cell proliferation via enhanced mitochondrial biogenesis. Cancer Biol Med. 2021 Feb 15;18(1):139-154. doi: 10.20892/j.issn.2095-3941.2020.0151. PMID: 33628590; PMCID: PMC7877175. 2. Hasan MR, Ho SH, Owen DA, Tai IT. Inhibition of VEGF induces cellular senescence in colorectal cancer cells. Int J Cancer. 2011 Nov 1;129(9):2115-23. doi: 10.1002/ijc.26179. Epub 2011 Aug 3. PMID: 21618508. 3. Lee Y, Kim SJ, Choo J, Heo G, Yoo JW, Jung Y, Rhee SH, Im E. miR-23a-3p is a Key Regulator of IL-17C-Induced Tumor Angiogenesis in Colorectal Cancer. Cells. 2020 Jun 1;9(6):1363. doi: 10.3390/cells9061363. PMID: 32492770; PMCID: PMC7348989. 4. Kubo K, Shimizu T, Ohyama S, Murooka H, Iwai A, Nakamura K, Hasegawa K, Kobayashi Y, Takahashi N, Takahashi K, Kato S, Izawa T, Isoe T. Novel potent orally active selective VEGFR-2 tyrosine kinase inhibitors: synthesis, structure-activity relationships, and antitumor activities of N-phenyl-N'-{4-(4-quinolyloxy)phenyl}ureas. J Med Chem. 2005 Mar 10;48(5):1359-66. doi: 10.1021/jm030427r. PMID: 15743179. |
| In vitro protocol: | 1. Ni H, Guo M, Zhang X, Jiang L, Tan S, Yuan J, Cui H, Min Y, Zhang J, Schlisio S, Ma C, Liao W, Nister M, Chen C, Li S, Li N. VEGFR2 inhibition hampers breast cancer cell proliferation via enhanced mitochondrial biogenesis. Cancer Biol Med. 2021 Feb 15;18(1):139-154. doi: 10.20892/j.issn.2095-3941.2020.0151. PMID: 33628590; PMCID: PMC7877175. 2. Hasan MR, Ho SH, Owen DA, Tai IT. Inhibition of VEGF induces cellular senescence in colorectal cancer cells. Int J Cancer. 2011 Nov 1;129(9):2115-23. doi: 10.1002/ijc.26179. Epub 2011 Aug 3. PMID: 21618508. |
| In vivo protocol: | 1. Lee Y, Kim SJ, Choo J, Heo G, Yoo JW, Jung Y, Rhee SH, Im E. miR-23a-3p is a Key Regulator of IL-17C-Induced Tumor Angiogenesis in Colorectal Cancer. Cells. 2020 Jun 1;9(6):1363. doi: 10.3390/cells9061363. PMID: 32492770; PMCID: PMC7348989. 2. Kubo K, Shimizu T, Ohyama S, Murooka H, Iwai A, Nakamura K, Hasegawa K, Kobayashi Y, Takahashi N, Takahashi K, Kato S, Izawa T, Isoe T. Novel potent orally active selective VEGFR-2 tyrosine kinase inhibitors: synthesis, structure-activity relationships, and antitumor activities of N-phenyl-N'-{4-(4-quinolyloxy)phenyl}ureas. J Med Chem. 2005 Mar 10;48(5):1359-66. doi: 10.1021/jm030427r. PMID: 15743179. |
1: Pan Z, Fukuoka S, Karagianni N, Guaiquil VH, Rosenblatt MI. Vascular endothelial growth factor promotes anatomical and functional recovery of injured peripheral nerves in the avascular cornea. FASEB J. 2013 Jul;27(7):2756-67. doi: 10.1096/fj.12-225185. Epub 2013 Apr 8. PubMed PMID: 23568776; PubMed Central PMCID: PMC3688738.
2: Xu C, Wu X, Zhu J. VEGF promotes proliferation of human glioblastoma multiforme stem-like cells through VEGF receptor 2. ScientificWorldJournal. 2013;2013:417413. doi: 10.1155/2013/417413. Epub 2013 Feb 28. PubMed PMID: 23533349; PubMed Central PMCID: PMC3603324.
3: Akiyama K, Ohga N, Hida Y, Kawamoto T, Sadamoto Y, Ishikawa S, Maishi N, Akino T, Kondoh M, Matsuda A, Inoue N, Shindoh M, Hida K. Tumor endothelial cells acquire drug resistance by MDR1 up-regulation via VEGF signaling in tumor microenvironment. Am J Pathol. 2012 Mar;180(3):1283-93. doi: 10.1016/j.ajpath.2011.11.029. Epub 2012 Jan 13. PubMed PMID: 22245726.
4: Arao T, Matsumoto K, Furuta K, Kudo K, Kaneda H, Nagai T, Sakai K, Fujita Y, Tamura D, Aomatsu K, Koizumi F, Nishio K. Acquired drug resistance to vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor in human vascular endothelial cells. Anticancer Res. 2011 Sep;31(9):2787-96. PubMed PMID: 21868521.
5: Hasan MR, Ho SH, Owen DA, Tai IT. Inhibition of VEGF induces cellular senescence in colorectal cancer cells. Int J Cancer. 2011 Nov 1;129(9):2115-23. doi: 10.1002/ijc.26179. Epub 2011 Aug 3. PubMed PMID: 21618508.
6: Kuo SW, Ke FC, Chang GD, Lee MT, Hwang JJ. Potential role of follicle-stimulating hormone (FSH) and transforming growth factor (TGFβ1) in the regulation of ovarian angiogenesis. J Cell Physiol. 2011 Jun;226(6):1608-19. doi: 10.1002/jcp.22491. PubMed PMID: 20945379.
7: Kubo K, Shimizu T, Ohyama S, Murooka H, Iwai A, Nakamura K, Hasegawa K, Kobayashi Y, Takahashi N, Takahashi K, Kato S, Izawa T, Isoe T. Novel potent orally active selective VEGFR-2 tyrosine kinase inhibitors: synthesis, structure-activity relationships, and antitumor activities of N-phenyl-N'-{4-(4-quinolyloxy)phenyl}ureas. J Med Chem. 2005 Mar 10;48(5):1359-66. PubMed PMID: 15743179.
