Fig. 6
From: Discovery of a novel and highly selective JAK3 inhibitor as a potent hair growth promoter
Preclinical safety and toxicity profile of MJ04. A Experimental Overview: The dorsal skin of C57BL/6J mice was shaved, and subsequent treatments were applied to the dorsal skin surface on the following day. B Acute Dermal Toxicity Assessment: Signal dose acute dermal toxicity tests were conducted in C57BL/6 mice. C Experimental overview of Median Lethal Dose (LD50) Determination: Acute dermal toxicity tests were conducted in Wistar rats. Limited testing included a single dose at 2 g/kg body weight. D Mean Weekly Body Weight: Monitoring of mean weekly body weight during the acute dermal toxicity assessment of MJ04. E Histopathological Analysis of dorsal skin tissue: Haematoxylin and eosin images depict the dorsal skin of mice (n = 5 mice per group). The histopathology images are presented at 10× magnification and show the skin of the control (a and b) and MJ04 treated group (2000 mg/kg) (c and d). F Mean serum biochemistry of acute dermal toxicity of MJ04. The values are expressed as mean ± SD (n = 3); *Significant difference from the control group at P < 0.05; b.w.: Body weight; GLU: Glucose, ALP: Alkaline Phosphatase, ALT: Alanine Transaminase, AST: Aspartate Amino Transferase, TB: Total Bilirubin, TG: Triglycerides, TP: Total Protein, ALB: Albumin, GLB: Globulin, CR: Creatinine, BUN: Blood Urea Nitrogen, Ca: Calcium, P: Phosphorus, Na: Sodium; No significant difference in the means of treatment groups and control group at 0.05 level. G Represents the metabolic stability of MJ04 in human liver microsomes. H–L shows the effect of MJ04 on hERG channel currents. Representative current traces show the effect of control (0.1% DMSO, black traces), 0.1 µM E-4031 (red traces), 10 µM Tofacitinib (green traces, H), 10 µM MJ04 (green traces, I). The recording protocol employed is shown in inset. J Mean tail current % inhibition for each drug is plotted. K, and L shows the summary dose response for 5 concentrations of the Tofacitinib (K) and MJ04 (L) ranging from 0.3 µm to 30 µM. Data points are the mean ± SEM (n = 3)