Table 2. The preclinical pharmacological study of LLDT-8 as an immunosuppressant drug candidate.

Compounds	Disease	Models	Regimens	Reported responses	Possible mechanism	Refs
LLDT-8	Rheumatoid arthritis	Collagen-induced arthritis in DBA/1 mice	po administrations for 3 months (0.125, 0.25, and 0.5 mg/kg, starting from 1 d before booster immunization)	Attenuated the severity of CIA	Blockade of IFN-γ signaling, IFN-γ related cytokine and chemokine	33
	Multiple sclerosis	MOG 35-55 induced EAE in mice	1 mg·kg−1·d−1 LLDT-8 ip from the day of EAE induction	Reduced the incidence and severity of EAE	Suppression of T cell proliferation and activation	36
	GVHD	Allo-BMT murine model (BLAB/c, H-2d to C57BL/6, H-2b) of aGVHD	1 mg·kg−1·d−1 administered orally starting on day of allo-BMT until the end of experiment	Prevented weight loss and death, extended survival of allo-BMT mice	Increased the CD4+CD25+T cells and up-regulated Foxp3 expression	32
	Transplantation	Balb/c to C57BL/6 murine cardiac transplantation model	LLDT-8 (1, 0.25 mg·kg−1·d−1) was administered orally starting on the transfer day until the end of experiment	Induced the survival prolongation of allogeneic cardiac graft	Reduced expression of chemokines and its receptor	38
	Acute Hepatitis	ConA-induced hepatitis in mice	Pretreatment with 0.5, 1, or 2 mg/kg LLDT-8 (by ip) four times (on d -3, -2, −1, and 1 h before conA injection)	Significantly increased the survival rates to 83%, 86% and 100%, respectively.	Blockade of IFN-γ/STAT1/IRF−1 signaling- and inflammatory mediators	37
	Lung fibrosis	Bleomycin-induced lung fibrosis	LLDT-8 (0.5, 1, and 2 mg/kg, ip) administered once daily for 7 or 14 consecutive days	Protective against bleomycin-induced lung fibrosis, alleviated the body weight loss and lung index increase caused by bleomycin, reduced neutrophils and lymphocytes in the BALF	Anti-inflammation, antioxidant, and cytokine inhibition	39