Table 2: Development status of SMIs that target TLR signaling pathway for SLE treatment.

From: Toll-like receptors: potential targets for lupus treatment

CompoundTargetChemical structureIndicationClinical phaseDosage regimenRef
HCQTLR7, TLR8 and TLR9 antagonistMalaria; Rheumatoid arthritis; SLELaunched-1956200-400 mg, once daily, po (patients)76,77,78,79,80,81
CpG-52364TLR7, TLR8 and TLR9 antagonistRheumatoid Arthritis; SLEPhase I1-100 mg, po(healthy objects, safety and tolerability study)82,83
SM934TLR7/9 signal transduction modulatorAutoimmune diseases; SLEIND Filed12.5 and 5 mg/kg, ig (MRL/lpr mice);
10 mg·kg−1·d−1, ig (NZB/W F1 mice)
84,85,86,87
E-6446TLR7, TLR9, and IL-6 antagonistAntimalarials; Sepsis;
Multiple sclerosis;
Rheumatoid arthritis; SLE
Preclinical20 and 60 mg/kg, ig (MRL/lpr mice)88
AT-791TLR7, TLR9, and IL-6 antagonistMultiple sclerosis;
Sepsis;
Rheumatoid arthritis; SLE
Preclinical20 mg/kg, ig (BALB/c mice)88
VTX-763TLR8 antagonist-Inflammation;
Autoimmune diseases
Preclinical--
TMX-302TLR7 antagonist-Antipsoriatics;
Autoimmune diseases
Preclinical--
IMO-9200TLR7, TLR8 and TLR9 antagonist-Autoimmune diseasesPhase I5 and 10 mg/kg, once/week, sc (MRL/lpr mice);
1.5 and 9 mg/kg, once/2 week, sc (monkeys)
89,90
ST-2825MyD88 dimerization inhibitorCancer; Viral infection;
Transplant rejection;
Arthritis; Autoimmune disease
Biological testing100 and 200 mg/kg, ig (C57BL/6 mice)91,92
AS-2444697IRAK4 inhibitorArthritis; Gout;
Sepsis; SLE
Preclinical0.3-3 mg/kg, bid, ig (5/6 Nx rats)93
PF-05387252IRAK4 inhibitorRheumatoid arthritis;
SLE
Preclinical--
PF-05388169IRAK4 inhibitorRheumatoid arthritis;
SLE
Preclinical--
PF-06650833IRAK4 inhibitor-SLEPhase I1-1000 mg of immediate release
10-500 mg of modified release (healthy objects, safety and tolerability study)
94
DZ2002TLR signal transduction modulator SLEPreclinical50 mg·kg−1·d−1, ip (BXSB mice);
50 mg·kg−1·d−1, ip (MRL/lpr mice);
0.5 mg·kg−1·d−1, ig (NZB/W F1 mice)
95,96
  1. 1IND: Investigational New Drug Application