DZ2002

Research use only, not for human use.

DZ2002, an orally active, reversible, and low-cytotoxic type III SAHH inhibitor (Ki=17.9 nM), exhibits significant immunosuppressive activity.

DZ2002 is an orally active, reversible and low-cytotoxic type III SAHH inhibitor (Ki=17.9 nM), with good immunosuppressive activity. DZ2002 prevents the development of experimental dermal fibrosis by reversing the profibrotic phenotype of various cell types. DZ2002 can be used in studies of autoimmune diseases such as lupus syndrome and systemic sclerosis.

DZ2002 (0.1, 1, 10 μM; 96 h) inhibits the mixed lymphocyte reaction (MLR) response.DZ2002 (0.1, 1, 10 μM; 24 h) inhibits IL-12 and TNF-α production from both mouse peritoneal exudate cells and humanTHP-1 Cells.DZ2002 (0.1, 1, 10 μM; 64 h) inhibits expression of B7 (CD80/CD86) on differentiated THP-1 cells.Cell Proliferation Assay Cell Line:BALB/c and C57BL/6 splenocytes (Mitomycin C-pretreated; mixed lymphocyte)Concentration:0.1, 1, 10 μM Incubation Time:96 h Result:Suppressed the MLR by 24.5, 42.3, and 46.0% at dosages of 0.1, 1, and 10 μM, respectively.Cell Viability Assay Cell Line:TG-stimulated mouse peritoneal macrophages and human THP-1 cells Concentration:0.1, 1, 10 μM Incubation Time:24 h Result:Significantly blocked IL-12 p40 production from ~1800 pg/mL in untreated cells to ~850 pg/ml at 10 μM, and drastically reduced the active p70 form from ~1200 pg/mL in untreated cells to ~50 pg/mL.Reduced TNF-α level by 45%.Cell Viability Assay Cell Line:THP-1 cells Concentration:0.1, 1, 10 μM Incubation Time:64 h Result:Dramatically down-regulated CD80 and, in particular, CD86 expression in a dose-dependent manner.

DZ2002 (2, 10, 50 mg/kg; i.p.; twice) blocks the DNFB-induced DTH response. (DNFB-induced DTH is a Th1 cell-mediated immune response, in which IL-12 is highly expressed and macrophages have been shown to play an important role).DZ2002 (0.08, 2 mg/kg; i.p.; single daily for 7 days) significantly suppresses a delayed-type hypersensitivity reaction as well as antibody secretion.DZ2002 (50, 100 mg/kg; p.o.; single daily for 4 weeks) exerts a potent anti-fibrotic effect on dermal fibrosis by reducing the production of collagen, facilitating its degradation and regulating expression of various soluble factors in SSc mice model.Animal Model:Male and female BALB/c and C57BL/6 mice (6 to 8-week-old; DNFB-induced ear swelling model).Dosage:2, 10, 50 mg/kg Administration:Intraperitoneal injection; twice (1 h before and 24 h after challenge)Result:Suppressed ear swelling by 19.1, 28.7, and 33.1%, respectively and in a dose-dependent manner.Animal Model:Male and female BALB/c and C57BL/6 mice (6 to 8-week-old; DNFB-induced ear swelling model).Dosage:0.08, 2 mg/kg Administration:Intraperitoneal injection; single daily for 7 days.Result:Inhibited hemolysis by 24.5 and 18.4% at doses of 0.08 and 2 mg/kg, respectively, thus decreasing anti-SRBC antibody production in vivo.Animal Model:Wild-type C57BL/6 mice (8 to 12-week-old; BLM-induced mice model of SSc).Dosage:50, 100 mg/kg Administration:Oral gavage; single daily for 4 weeks.Result:Significantly decreased skin thickness and dermal thickness in BLM-induced mice.Significantly reduced collagen accumulation and α-SMA expression in the dermis of mice and suppressed the mRNA expression of vascular endothelial growth factor (VEGF) in mice skin tissue.Notably reduced collagen content and mRNA expression of the Col1a1 and Col1a2 while promoting that of the matrix metalloproteinase-13 (MMP-13) in the lesional skin of BLM-induced mice.

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Others

Other Targets

Others

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33231-14-0

251.24

C10H13N5O3

>98% (HPLC)

In Vitro:?DMSO : ≥ 61 mg/mL (242.80 mM )

COC(=O)C(O)CCn1cnc2c(N)ncnc12

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(-20℃)

With Ice Pack

≥ 2 years