SM 934

• Ethanamine, 2-[(decahydro-3,6,9-trimethyl-3,12-epoxy-12H-pyrano[4,3-j]-1,2-benzodioxepin-10-yl)oxy]-, [3R-(3α,5aβ,6β,8aβ,9α,10α,12β,12aR*)]-, (Z)-2-butenedioate (1:1)
• 3,12-Epoxy-12H-pyrano[4,3-j]-1,2-benzodioxepin, ethanamine deriv.
• SM 934
• β-Aminoarteether maleate

TLR7/9 signal transduction modulator

IND FILED

2.5 and 5 mg/kg, ig (MRL/lpr mice);
10 mg·kg⁻¹·d⁻¹, ig (NZB/W F1 mice)

Autoimmune diseases; SLE

SM934, an artemisinin derivative, possesses potent antiproliferative and antiinflammatory properties.

In the present study, we investigated the immunosuppressive effects and underlying mechanisms of beta-aminoarteether maleate (SM934), a derivative of artemisinin, against T cell activation in vitro and in vivo. In vitro, SM934 significantly inhibited the proliferation of splenocytes induced by concanavalin A (Con A), lipopolysaccharide (LPS), mixed lymphocyte reaction (MLR), and anti-CD3 plus anti-CD28 (anti-CD3/28). SM934 significantly inhibited interferon (IFN)-gamma production and CD4(+) T cell division stimulated by anti-CD3/28. SM934 also promoted apoptosis of CD69(+) population in CD4(+) T cells stimulated by anti-CD3/28. Furthermore, SM934 inhibited interleukin (IL)-2 mediated proliferation and survival through blocking Akt phosphorylation in activated T cells. In ovalbumin (OVA)-immunized mice, oral administration of SM934 suppressed OVA-specific T cell proliferation and IFN-gamma production. SM934 treatment also significantly inhibited the sheep red blood cell (SRBC)-induced delayed type hypersensitivity (DTH) reactions in mice. Taken together, SM934 showed potent immunosuppressive activities in vitro and in vivo. Our results demonstrated that SM934 might be a potential therapeutic agent for immune-related diseases.

PATENT

http://www.google.co.in/patents/EP0362730A1?cl=en

PAPER

Volume 9, Issues 13–14, December 2009, Pages 1509–1517

Inflammatory Mediators Long Term after Sulfur Mustard Exposure (Sardasht-Iran Cohort Study)

SM934, a water-soluble derivative of arteminisin, exerts immunosuppressive functions in vitro and in vivo

• Li-Fei Hou^a,
• Shi-Jun He^a,
• Jun-Xia Wang^a,
• Yang Yang^c,
• Feng-Hua Zhu^a,
• Yu Zhou^a,
• Pei-Lan He^a,
• Yu Zhang^b,
• Yi-Fu Yang^c,
• Ying Li^{b, ,} ,
• Wei Tang^{a, ,} ,
• Jian-Ping Zuo^{a, c, ,}

• ^a State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China
• ^b Department of Synthetic Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People’s Republic of China
• ^c Laboratory of Immunology and Virology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, People’s Republic of China

• Hou LF, He SJ, Wang JX, Yang Y, Zhu FH, Zhou Y, et al. SM934, a water-soluble derivative of arteminisin, exerts immunosuppressive functions in vitro and in vivo. Int Immunopharmacol 2009; 9: 1509–17. | Article |
• Hou LF, He SJ, Li X, Yang Y, He PL, Zhou Y, et al. Oral administration of artemisinin analog SM934 ameliorates lupus syndromes in MRL/lpr mice by inhibiting Th1 and Th17 cell responses. Arthritis Rheum 2011; 63: 2445–55. | Article
• Hou LF, He SJ, Li X, Wan CP, Yang Y, Zhang XH, et al. SM934 treated lupus-prone NZB x NZW F1 mice by enhancing macrophage interleukin-10 production and suppressing pathogenic T cell development. PLoS One 2012; 7: e 32424.
• Wu Y, He S, Bai B, Zhang L, Xue L, Lin Z, et al. Therapeutic effects of the artemisinin analog SM934 on lupus-prone MRL/lpr mice via inhibition of TLR-triggered B-cell activation and plasma cell formation. Cell Mol Immunol 2015 Mar 16. doi: 10.1038/cmi.2015.13. [Epub ahead of print].

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