E7820 (ER68203-00), an orally active aromatic sulfonamide derivative, is a unique angiogenesis inhibitor that suppresses the expression of the integrin alpha2 subunit on endothelial cells. It inhibits angiogenesis in rat aorta with an IC50 of 0.11 µg/ml and affects the expression of α-1, α-2, α-3, and α-5 integrin mRNA. E7820 displays antiangiogenic and antitumor activity[1][2].
体内研究
E7820 (ER68203-00) administered at 50-200 mg/kg, orally twice daily for 14 days, delays the growth of subcutaneously inoculated WiDr cells[1].
E7820, given at 200-400 mg/kg orally once daily for four days, strongly inhibits angiogenesis induced by WiDr cells[1].
体外研究
E7820 inhibits both bFGF- and VEGF-driven tube formation in human umbilical vascular endothelial cells (HUVEC) in a dose-dependent manner with IC50 values of 0.20 µg/ml and 0.24 µg/ml, respectively[1].
E7820 suppresses HUVEC proliferation induced by bFGF or VEGF in serum-free medium (SFM), with IC50 values of 0.10 and 0.081 μg/ml, respectively. Compared to its effect on HUVEC, E7820 demonstrates minimal antiproliferative activity against WiDr and LoVo cells, with IC50 values of 29 and 15 μg/ml, respectively[1].
E7820 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HUVECs
50 ng/ml
17 hours
E7820 decreased integrin α2 expression in HUVECs
BMC Cancer. 2021 May 18;21(1):571
MC3T3 cells
50 ng/ml
17 hours
E7820 increased integrin α2 expression in MC3T3 cells
BMC Cancer. 2021 May 18;21(1):571
H1650 cells
3 μM
96 hours
To evaluate the effect of E7820 in combination with erlotinib on proliferation and apoptosis of H1650 cells. Results showed that the combination significantly inhibited H1650 cell growth and enhanced apoptosis.
Cancer Sci. 2014 Aug;105(8):1023-31
H1975 cells
3 μM
96 hours
To evaluate the effect of E7820 in combination with erlotinib on proliferation and apoptosis of H1975 cells. Results showed that the combination did not significantly inhibit H1975 cell growth or induce apoptosis.
Cancer Sci. 2014 Aug;105(8):1023-31
A549 cells
3 μM
96 hours
To evaluate the effect of E7820 in combination with erlotinib on proliferation and apoptosis of A549 cells. Results showed that the combination did not significantly inhibit A549 cell growth or induce apoptosis.
Cancer Sci. 2014 Aug;105(8):1023-31
HUVECs
3 μM
48 hours
To evaluate the effect of E7820 in combination with erlotinib on proliferation and apoptosis of HUVECs. Results showed that the combination significantly inhibited HUVEC growth and enhanced apoptosis.
Cancer Sci. 2014 Aug;105(8):1023-31
eEnd2 cells
50 ng/ml
17 hours
E7820 did not significantly alter integrin α2 expression in eEnd2 cells
BMC Cancer. 2021 May 18;21(1):571
Saos-2 cells
50 ng/ml
17 hours
E7820 did not significantly alter integrin α2 expression in Saos-2 cells
BMC Cancer. 2021 May 18;21(1):571
DLD1-KO (BRCA2 knockout)
1 µM
72 hours
Evaluate DNA double-strand break induction and sensitivity of E7820 in BRCA2-deficient cells. Results showed significant γH2AX induction and RBM39 degradation in DLD1-KO cells with higher sensitivity than parental cells.
NPJ Precis Oncol. 2024 May 24;8(1):117
HCT116 cells
1 μM
12 hours
E7820 suppressed ARNT levels and promoted proteasomal degradation of ARNT through interaction with DCAF15.
Mol Cells. 2020 Nov 30;43(11):935-944
HEK293T cells
1 μM
12 hours
E7820 suppressed ARNT levels and promoted proteasomal degradation of ARNT through interaction with DCAF15.
Mol Cells. 2020 Nov 30;43(11):935-944
Kelly cells
10 μM
5 hours
To evaluate the degradation effect of E7820 on RBM39 and RBM23
Nat Chem Biol. 2020 Jan;16(1):7-14
NCI-H1299 cells
1 µM
72 hours
Suppressed MTX-induced EMT-related phenotypic changes, such as morphology and mRNA and protein expression of α-smooth muscle actin
Toxicol Res. 2022 Mar 16;38(4):449-458
A549 cells
1 µM
72 hours
Suppressed MTX-induced EMT-related phenotypic changes, such as morphology and mRNA and protein expression of α-smooth muscle actin
Toxicol Res. 2022 Mar 16;38(4):449-458
E7820 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
NOG mice
Patient-derived xenograft (PDX) models
Oral
100 mg/kg or 200 mg/kg
Daily for 21 days
Evaluate antitumor efficacy of E7820 in diverse solid tumor PDX models. Overall response rate was 38.1% (16/42), with highest sensitivity in bile duct cancer (58.3%). Loss-of-function mutations in HRR genes (e.g., ATM) significantly correlated with sensitivity (p=4.5×10^-3).
NPJ Precis Oncol. 2024 May 24;8(1):117
Nude mice
Non-small-cell lung cancer xenograft models
Oral
E7820: 25 or 50 mg/kg; erlotinib: 60 mg/kg
E7820: twice daily; erlotinib: once daily; for 3 weeks
To evaluate the antitumor activity of E7820 in combination with erlotinib in EGFR-TKI-resistant non-small-cell lung cancer xenograft models. Results showed that the combination exhibited a synergistic antitumor effect in three xenograft models, significantly decreasing microvessel density and increasing apoptosis of tumor-associated endothelial cells.
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