Drug repositioning and the candidates' mechanism of action for vitiligo

Aim: Vitiligo is a complex disease with hypochromic or achromic spots [۱]. Topicaltreatment drugs are not ۱۰۰% effective and are also associated with side effects [۱–۳]. Method: Tointroduce new drug candidates for vitiligo, we have made a systematic search in the GEO Ncbi. Arraydata were selected and filtered by parameters of lesional and non-lesional samples. Meta-analysis wasperformed using the ImaGEO online tool [۴]. Differentially expressed genes were used as signaturesfor screening against drugs in the connectivity map database. Finally, the results were filtered based onthe highest Z score and MOA classification [۵,۶]. The highest reverse Z score (z score<-۸۰) was usedfor target prediction using Swiss target prediction. The drug-target network was constructed, and thetarget nodes with the highest degree were identified. Findings: Twenty-eight genes were significantafter a meta-analysis of the two datasets of GSE۷۵۸۱۹ and GSE۶۵۱۲۷ with a total of ۳۸ samples. ۱۰۰۲compounds were identified with reverse profiles. The compound with the highest z score includes CDK,DNA synthesis, HDAC, IGF-۱, JAK, JNK, MEK, mTOR inhibitors, and Glucocorticoid receptoragonists. The highest degree nodes in the constructed target-compound network were enriched in themost significant pathways in cancer, PI۳K-Akt signaling pathway, Ras signaling pathway, and EGFRTyrosine Kinase Inhibitor Resistance.Conclusion: There are a couple of candidates that have not previously been proposed for vitiligotreatment and as therapy candidates worth examining. Based on the drug target network, some cancerpathways are also involved in vitiligo, which indicates the shared pathways of cancer and vitiligo.

کلیدواژه ها:

Vitiligo ، Drug repositioning ، Connectivity map