1.MOA

Target X, a novel target, is mainly expressed in bone marrow and lymphatic tissue，especially in NK cells, T cells, B cells, monocytes, DC cells and Hofbauer cells

The levels of Th1 cells and Th 17 cells are upregulated and the levels of Th2 cells and Treg cells are decreased in Target X mutantmice and Target X knockout mice；

ASSET can reduce the levels of Th1 cells and Th 17 cells and upregulate the levels of Th 1 cells and Treg cellsin Target X mutant mice, but has no effect in Target X knockout mice；

2. Data and results

The efficacy of ASSET on SLE in mice
ASSET improved general condition and decreased mortality of SLE mice.
ASSET significantly reduced the level of serum dsDNA antibody with dose dependent manner and better efficacy the positive control；
ASSET significantly reduce and even eliminate the subcutaneous nodules in SLE
ASSET significantly alleviated renal injury, reduced renal inflammatory cell infiltration.
ASSET decreased the urinary protein and improved renal function;
ASSET significantly improved mesangial cell proliferation and basement membrane thickening.
ASSET significantly reduced the deposition of antigen-antibody complex on glomerular basement membrane.

The efficacy of ASSET on Ankylosing spondylitis in SKG mice
ASSET alleviates the clinical symptoms, improves survival rate and increases bone mineral density of mice with mandatory spondylitis.;

CT imaging scores

The efficacy of ASSET on acute UC
ASSET increased body weight, survival rate and significantly reduced DAI score of mice with Ulcerative colitis；
ASSET can significantly reduce colon shortening and swelling in mice with acute colitis；
ASSET significantly inhibited the decrease of Occludin in acute ulcerative colitis mice, restoring the intestinal barrier, with a better efficacy than positive drugs；

The efficacy of ASSET on chronic UC
ASSET can reduce the weight loss and DAI score of mice with chronic colitis.
ASSET can significantly reduce colon shortening and swelling in mice with chronic colitis
ASSET significantly alleviated the pathological changes of colon in mice with chronic UC, with a better efficacy than positive drug
ASSET significantly inhibited the decrease of Occludin in chronic ulcerative colitis mice, restoring the intestinal barrier, with a better efficacy than positive drug；

SignificantSafety
Subacute toxicity: Asset at 5/10/20 mg/kg, and no target organ toxicity or weight loss was observed
Replication at higher dosage: 25mg/kg, 75 mg/kg, 150mg/kg per day, repeated by gavage for 28 days
Mortality: no deaths or dying rats in all doses
The main toxic reactions(mostly occurring in the high-dose group)

Bowed back，emaciation，bristle，and lose weight and food intake in the high-dose group
NEUT% increases，WBC count, LYMPH%, MONO% and EO% decreased

The maximum tolerable dose(MTD) is 150mg/kg, and the NOEAL about 20 mg/kg（at least 10 times higher than the therapeutic dose）