WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 201090
CAS#: 289483-69-8
Description: E7820 is a α2 integrin inhibitor with potential antiangiogenic and antitumor activities. E7820 inhibits angiogenesis by suppressing integrin alpha 2, a cell adhesion molecule expressed on endothelial cells. Inhibition of integrin alpha 2 leads to an inhibition of cell-cell interactions, endothelial cell-matrix interactions, vascular endothelial cell proliferation and angiogenesis.
MedKoo Cat#: 201090
Name: E7820
CAS#: 289483-69-8
Chemical Formula: C17H12N4O2S
Exact Mass: 336.0681
Molecular Weight: 336.37
Elemental Analysis: C, 60.70; H, 3.60; N, 16.66; O, 9.51; S, 9.53
Synonym: E7820; E-7820; E 7820.
IUPAC/Chemical Name: N-(3-cyano-4-methyl-1H-indol-7-yl)-3-cyanobenzene-sulfonamide
InChi Key: LWGUASZLXHYWIV-UHFFFAOYSA-N
InChi Code: InChI=1S/C17H12N4O2S/c1-11-5-6-15(17-16(11)13(9-19)10-20-17)21-24(22,23)14-4-2-3-12(7-14)8-18/h2-7,10,20-21H,1H3
SMILES Code: O=S(C1=CC=CC(C#N)=C1)(NC2=CC=C(C)C3=C2NC=C3C#N)=O
Appearance: 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: 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: >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: 2934.99.9001
| Biological target: | E7820 (ER68203-00) is a unique angiogenesis inhibitor suppressing an expression of integrin alpha2 subunit on endothelium. |
| In vitro activity: | E7820 treatment at 0.05 μg/ml for 48 h altered the pattern of integrin expression on the cell surface of HUVEC under both subconfluent and confluent culture conditions. The expression level of integrin α2 was significantly decreased to ∼50% of the control under both culture conditions (Fig. 2, b and c). Integrins α3 and 5 were also decreased, although to lesser extents than α2 subunit. The expression level of α6 subunit was significantly down-regulated to 60% of the control in subconfluent culture, but it remained at 90% of the control in confluent culture. E7820 treatment did not alter the expression of αv integrin or CD31 under these culture conditions. TNP-470 at 0.05 μg/ml did not affect the pattern of integrin expression under the confluent culture condition (data not shown). After 12 h treatment of HUVEC with E7820 (0.05 μg/ml), integrin α2 mRNA was significantly decreased, whereas other integrin subunits including CD31 and VE-cadherin were not altered (Fig. 3a). E7820 suppressed integrin α2 mRNA after 6 h of treatment, indicating that E7820 acts initially on integrin α2 followed by integrins α3, 5, and β1 (Fig. 3b). The inhibition of integrin α2 expression in HUVEC showed dose dependence, but E7820 did not alter the level of CD31 even at the concentration of 0.5 μg/ml (Fig. 4). Furthermore, because the activity of E7820 toward integrin α2 was not observed in a human fibroblast cell line (WI-38; data not shown), the inhibitory action of E7820 might be selective to certain cell types. Reference: Cancer Res. 2002 Nov 1;62(21):6116-23. http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=12414636 |
| In vivo activity: | Oral administration of E7820, once daily for 4 days, at the doses of 200 and 400 mg/kg, potently inhibited WiDr-induced angiogenesis (Fig. 7a). Immunohistochemical analysis showed that newly formed vessels appeared beneath the muscle layer in the skin, whereas such a vessel-enriched layer was not found in mice given 400 mg/kg E7820 (Fig. 7b). Because WiDr cells are extremely less sensitive toward E7820 in cell growth assay (see below), the effect in DAS model strongly suggests an antiangiogenic potency of E7820. Moreover, E7820 (oral administration twice daily for 14 days) significantly delayed the growth of WiDr cells inoculated s.c. The antitumor effect was dose-dependent at 50, 100, and 200 mg/kg, and the tumor growth rates after the beginning of E7820 treatment (ΔT/C value) were 52%, 46%, and 27%, respectively (Fig. 8a). E7820 also completely suppressed the growth of human colorectal tumor, LoVo cells, on the same administration schedule for 21 days at the doses of 100 and 200 mg/kg (Fig. 8b). Antiproliferative activity of E7820 in vitro against both WiDr and LoVo cells was very weak compared with that against HUVEC. The values of IC50 were 29 and 15 μg/ml, respectively, suggesting that the antitumor effects of E7820 resulted from antiangiogenic activity. Reference: Cancer Res. 2002 Nov 1;62(21):6116-23. http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=12414636 |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 67.0 | 199.19 |
The following data is based on the product molecular weight 336.37 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 |
| In vitro protocol: | 1. Funahashi Y, Sugi NH, Semba T, Yamamoto Y, Hamaoka S, Tsukahara-Tamai N, Ozawa Y, Tsuruoka A, Nara K, Takahashi K, Okabe T, Kamata J, Owa T, Ueda N, Haneda T, Yonaga M, Yoshimatsu K, Wakabayashi T. Sulfonamide derivative, E7820, is a unique angiogenesis inhibitor suppressing an expression of integrin alpha2 subunit on endothelium. Cancer Res. 2002 Nov 1;62(21):6116-23. PMID: 12414636. 2. Semba T, Funahashi Y, Ono N, Yamamoto Y, Sugi NH, Asada M, Yoshimatsu K, Wakabayashi T. An angiogenesis inhibitor E7820 shows broad-spectrum tumor growth inhibition in a xenograft model: possible value of integrin alpha2 on platelets as a biological marker. Clin Cancer Res. 2004 Feb 15;10(4):1430-8. doi: 10.1158/1078-0432.ccr-0109-03. PMID: 14977846. |
| In vivo protocol: | 1. Funahashi Y, Sugi NH, Semba T, Yamamoto Y, Hamaoka S, Tsukahara-Tamai N, Ozawa Y, Tsuruoka A, Nara K, Takahashi K, Okabe T, Kamata J, Owa T, Ueda N, Haneda T, Yonaga M, Yoshimatsu K, Wakabayashi T. Sulfonamide derivative, E7820, is a unique angiogenesis inhibitor suppressing an expression of integrin alpha2 subunit on endothelium. Cancer Res. 2002 Nov 1;62(21):6116-23. PMID: 12414636. 2. Semba T, Funahashi Y, Ono N, Yamamoto Y, Sugi NH, Asada M, Yoshimatsu K, Wakabayashi T. An angiogenesis inhibitor E7820 shows broad-spectrum tumor growth inhibition in a xenograft model: possible value of integrin alpha2 on platelets as a biological marker. Clin Cancer Res. 2004 Feb 15;10(4):1430-8. doi: 10.1158/1078-0432.ccr-0109-03. PMID: 14977846. |
1: Ito K, Semba T, Uenaka T, Wakabayashi T, Asada M, Funahashi Y. Enhanced anti-angiogenic effect of E7820 in combination with erlotinib in epidermal growth factor receptor-tyrosine kinase inhibitor-resistant non-small-cell lung cancer xenograft models. Cancer Sci. 2014 Aug;105(8):1023-31. doi: 10.1111/cas.12450. PubMed PMID: 24841832.
2: Geramizadeh B, Asadian F, Taghavi A. Esophageal melanocytosis in oral opium consumption. Iran Red Crescent Med J. 2014 Jan;16(1):e7820. doi: 10.5812/ircmj.7820. Epub 2014 Jan 5. PubMed PMID: 24719715; PubMed Central PMCID: PMC3964433.
3: Semba T. [Current status of combination therapies of angiogenesis inhibitors: vascular normalization activity of a novel angiogenesis inhibitor E7820]. Nihon Yakurigaku Zasshi. 2013 Jan;141(1):4-8. Review. Japanese. PubMed PMID: 23302941.
4: Davies E. Former Bush adviser is appointed to lead Global Fund. BMJ. 2012 Nov 16;345:e7820. doi: 10.1136/bmj.e7820. PubMed PMID: 23160969.
5: Keizer RJ, Funahashi Y, Semba T, Wanders J, Beijnen JH, Schellens JH, Huitema AD. Evaluation of α2-integrin expression as a biomarker for tumor growth inhibition for the investigational integrin inhibitor E7820 in preclinical and clinical studies. AAPS J. 2011 Jun;13(2):230-9. doi: 10.1208/s12248-011-9260-2. Epub 2011 Mar 9. PubMed PMID: 21387147; PubMed Central PMCID: PMC3085714.
6: Mita M, Kelly KR, Mita A, Ricart AD, Romero O, Tolcher A, Hook L, Okereke C, Krivelevich I, Rossignol DP, Giles FJ, Rowinsky EK, Takimoto C. Phase I study of E7820, an oral inhibitor of integrin alpha-2 expression with antiangiogenic properties, in patients with advanced malignancies. Clin Cancer Res. 2011 Jan 1;17(1):193-200. doi: 10.1158/1078-0432.CCR-10-0010. PubMed PMID: 21208908.
7: Paolillo M, Russo MA, Serra M, Colombo L, Schinelli S. Small molecule integrin antagonists in cancer therapy. Mini Rev Med Chem. 2009 Oct;9(12):1439-46. Review. PubMed PMID: 19929817.
8: Li MY, Lai FJ, Hsu LJ, Lo CP, Cheng CL, Lin SR, Lee MH, Chang JY, Subhan D, Tsai MS, Sze CI, Pugazhenthi S, Chang NS, Chen ST. Dramatic co-activation of WWOX/WOX1 with CREB and NF-kappaB in delayed loss of small dorsal root ganglion neurons upon sciatic nerve transection in rats. PLoS One. 2009 Nov 12;4(11):e7820. doi: 10.1371/journal.pone.0007820. PubMed PMID: 19918364; PubMed Central PMCID: PMC2771921.
9: Keizer RJ, Zamacona MK, Jansen M, Critchley D, Wanders J, Beijnen JH, Schellens JH, Huitema AD. Application of population pharmacokinetic modeling in early clinical development of the anticancer agent E7820. Invest New Drugs. 2009 Apr;27(2):140-52. doi: 10.1007/s10637-008-9164-x. Epub 2008 Aug 20. PubMed PMID: 18712503.
10: Tucker GC. Integrins: molecular targets in cancer therapy. Curr Oncol Rep. 2006 Mar;8(2):96-103. Review. PubMed PMID: 16507218.
11: Semba T, Funahashi Y, Ono N, Yamamoto Y, Sugi NH, Asada M, Yoshimatsu K, Wakabayashi T. An angiogenesis inhibitor E7820 shows broad-spectrum tumor growth inhibition in a xenograft model: possible value of integrin alpha2 on platelets as a biological marker. Clin Cancer Res. 2004 Feb 15;10(4):1430-8. PubMed PMID: 14977846.
12: Funahashi Y, Sugi NH, Semba T, Yamamoto Y, Hamaoka S, Tsukahara-Tamai N, Ozawa Y, Tsuruoka A, Nara K, Takahashi K, Okabe T, Kamata J, Owa T, Ueda N, Haneda T, Yonaga M, Yoshimatsu K, Wakabayashi T. Sulfonamide derivative, E7820, is a unique angiogenesis inhibitor suppressing an expression of integrin alpha2 subunit on endothelium. Cancer Res. 2002 Nov 1;62(21):6116-23. PubMed PMID: 12414636.
Oral administration of E7820 significantly inhibited basic fibroblast growth factor-induced angiogenesis in Matrigel implants and human colon WiDr tumor-induced angiogenesis in a dorsal air sac model. Twice-daily treatment with E7820 clearly inhibited the s.c. tumor growth of seven tumor cell lines derived from human colon, breast, pancreas, and kidney, and completely suppressed the growth of human pancreatic KP-1 and human colon LoVo cell lines. Moreover, E7820 significantly inhibited the growth of KP-1 and human colon tumor Colo320DM cells orthotopically implanted in the pancreas and cecum, respectively. The efficacy of E7820 was comparable in the s.c. and orthotopic transplantation models. Immunohistochemical analyses using anti-CD31 antibody showed that E7820 significantly reduced microvessel density in orthotopically implanted KP-1 tumor. E7820 reduced integrin alpha2 expression on a megakaryocytic cell line, Dami cells, induced by phorbol 12-myristate 13-acetate treatment. It also decreased the expression level of integrin alpha2 on platelets withdrawn from mice bearing s.c. KP-1 tumor at a dosage close to that affording antitumor activity. These data demonstrate that E7820 showed a broad-spectrum antitumor effect in mice through inhibition of angiogenesis and indicate that the decrease of integrin alpha2 on platelets might serve as a biological marker for the antitumor efficacy of E7820. see http://www.ncbi.nlm.nih.gov/pubmed/14977846
