Methimazole (Synonyms: NSC 38608)

Methimazole (MMI) is an inhibitor of ICAM-1 (intercellular adhesion molecule-1) gene transcription via modulating the function of STAT1 (signal transducer and activator of transcription 1) [1].
ICAM-1 (intercellular adhesion molecule-1), also named as CD54, is a member of IGSF (immunoglobulin super-family adhesion molecule) which is expressed on endothelial cells and immune system cells [2]. It is encoded by ICAM-1 gene, ICAM-1 functions via binding to LFA-1 (lymphocyte function associated molecule-1) or Mac-1. It has shown that ICAM-1 abnormally expressed in patients with autoimmune thyroid diseases. Through modulating the function of STAT1 (signal transducer and activator of transcription 1), methimazole could inhibit the transcription of ICAM-1[1].
Methimazole is an inhibitor of ICAM-1 expression while H2O2 and IFN-γ both could heavily enhance the expression of ICAM-1. When tested with the modified FRTL-5 rat thyroid cells, using 500 μM methimazole pretreated the cells could inhibit the induction of ICAM-1 RNA by H2O2 and IFN-γ [1].
In tadpoles with methimazole treatment, the gene expression of thyroid hormone response was increased [3]. Through administering rats with methimazole, the CH (congenital hypothyroidism) offspring could be obtained for further research [4]. In the study, Sprague Dawley rats could be made as hypothyroid model for further research via giving 0.025% methimazole [5]. Using pregnant C57Bl/6 mice model, it was shown that methimazole could be used for mice or rat without causing gross external malformations [6].
References:
1.Kim, H., et al., Methimazole as an antioxidant and immunomodulator in thyroid cells: mechanisms involving interferon-gamma signaling and H(2)O(2) scavenging. Mol Pharmacol, 2001. 60(5): p. 972-80.
2.Kojima, R., M. Kawachi, and M. Ito, Butein suppresses ICAM-1 expression through the inhibition of IkappaBalpha and c-Jun phosphorylation in TNF-alpha- and PMA-treated HUVEC. Int Immunopharmacol, 2014. 19(14): p. 00484-6.
3.Choi, J., et al., Unliganded thyroid hormone receptor alpha regulates developmental timing via gene repression as revealed by gene disruption in Xenopus tropicalis. Endocrinology, 2014. 2.
4.O'Hare, E., et al., Effects of thyroxine treatment on histology and behavior using the methimazole model of congenital hypothyroidism in the rat. Neuroscience, 2014. 20: p. 128-138.
5.Herwig, A., et al., A thyroid hormone challenge in hypothyroid rats identifies t3 regulated genes in the hypothalamus and in models with altered energy balance and glucose homeostasis. Thyroid, 2014. 24(11): p. 1575-93.
6.Mallela, M.K., et al., Evaluation of developmental toxicity of propylthiouracil and methimazole. Birth Defects Res B Dev Reprod Toxicol, 2014. 101(4): p. 300-7.