Streptonigrin

Streptonigrin (Bruneomycin) is an orally active antibiotic and pan-PAD inhibitor, inhibiting PAD1, PAD2, PAD3 and PAD4 with IC₅₀ of 48.3 μM, 26.1 μM, 0.43 μM and 2.5 μM, respectively. Streptonigrin inhibits SENP1 (IC₅₀ of 0.518 μM) and reduces HIF1α. Streptonigrin increases p53 and Apoptosis. Streptonigrin shows antiviral activity against Rauscher murine leukemia virus. Streptonigrin has immunosuppressive effects. Streptonigrin has antitumor activity against osteosarcoma^{[1][2][3][4][5][6][7][8][9][10]}. IC50 & Target:IC50: 48.3 µM (PAD1), 26.1 µM, (PAD2), 0.43 µM (PAD3), 2.5 µM (PAD4), 0.518 μM (SENP1) In Vitro: Streptonigrin (10 μM) shows cytotoxicity towards both cancerous U2OS and normal NIH 3T3 cell lines^[1].
Streptonigrin (0-5 μM; 24 h) inhibits the proliferation of SW480 cells, AGS cells and HEK293 cells transfected with β-catenin in a dose-dependent manner^[2].
Streptonigrin (0.1-5 μM) does not influence the basal activity of soluble guanylate cyclase but causes concentration-dependent inhibition of enzyme activation by SNP (IC₅₀ of 4.16 μM) and also by spermineNONO^[3].
Streptonigrin (0-1 μM; 10 min) inhibits SENP1 activity with an IC₅₀ of 0.518 μM when SUMO1 is used as a substrate^[4].
Streptonigrin (2 μM; 16 h) reduces HIF1α protein level in HCT116 cells transfected with HIF1α expression plasmid^[4].
Streptonigrin (1 nM-10 μM; 4 h) shows a concentration-dependent effect on nuclear morphology in NIH 3T3 cells, promoting heterochromatin formation^[5].
Streptonigrin (2.5-500 μM; 60 min) inhibits the catalytic activity of purified calf thymus DNA topoisomerase II by relaxation of pBR322 DNA^[6].
Streptonigrin (72 h) selectively suppresses B-cell proliferation induced by LPS, with an IC₅₀ value of 0.29 ng/mL^[8].
Streptonigrin (10-100 nM) increases p53 and Apoptosis in ACHN and CAKI-1 cells^[9].
In Vivo: Streptonigrin (0.2 mg/kg; i.p or 0.5 mg/kg; p.o.) shows antiviral activity in mice infected with the Rauscher murine leukemia virus, reducing the spleen weight^[7].
Streptonigrin (0.1-0.2 mg/kg; i.p.; on day 0, 2, 4, and 6; until day 7) significantly suppresses the proliferative response of T-cells rather than that of B-cells in C57BL/6 mice^[8].
Streptonigrin (0.1 mg/kg; p.o.; once a day; 5 days a week) increases the expression of p53 in tumors, and decreases the expression of Ki67 in the xenograft model of human renal cell carcinoma in BALB/c nude mice^[9].