ISO-1 (Synonyms: ISO1, Macrophage Migration Inhibitory Factor)

ISO-1 inhibited MIF tautomerase activity in a dose-dependent manner with an IC50 of about 7 uµ^[1].

Treatment of the transfected cells with ISO-1 inhibited the release of arachidonic acid in a dose-dependent manner, the MIF inhibitory activities of ISO-1 and its derivatives were not the result of cell toxicity^[1]. In monocytes, ISO-1 caused marked suppression of TLR4-induced proinflammatory cytokine production, and to a lesser extent suppression of TLR2-induced responses^[6].

ISO-1 inhibits tumor necrosis factor release from macrophages isolated from LPStreated wild type mice but has no effect on cytokine release from MIFdeficient macrophages^[2]. ISO-1 exerts anti-cancer effects on PANC-1 cell proliferation, migration and invasion in vitro, and inhibited PANC-1 cell-induced tumour growth in xenograft mice in vivo^[3]. ISO-1 treatment alleviated pathological damage in pancreatic and renal tissues, and reduced the serum levels of amylase, lipase, creatinine, uric acid, IL-6 and TNF-α. ISO-1 also reduced protein expression of NLRP3, ASC, caspase-1 and IL-1β, mRNA expression of MIF, IL-6, TNF-α, IL-1β and IL-18, and the infiltration of MPO-positive neutrophils in kidney tissue^[4]. ISO-1 may protect the IBD cells, reduce pathological injuries, and reduce the inflammatory response in SAP rats. Its mechanisms may be via inhibiting the expression of MIF and then blocking the activation of p38-MAPK and NF-κB signaling pathway^[5]. ISO-1 remarkably improved the histological findings of APAP-induced liver injury in mice. The increases in serum levels of alanine aminotransferase (ALT), and macrophage inflammatory protein-2 (MIP-2) by APAP were inhibited by ISO-1^[7].

References:
[1]. Lubetsky JB, Dios A, et,al.The tautomerase active site of macrophage migration inhibitory factor is a potential target for discovery of novel anti-inflammatory agents. J Biol Chem. 2002 Jul 12;277(28):24976-82. doi: 10.1074/jbc.M203220200. Epub 2002 May 7. PMID: 11997397.
[2]. Al-Abed Y, Dabideen D, et,al. ISO-1 binding to the tautomerase active site of MIF inhibits its pro-inflammatory activity and increases survival in severe sepsis. J Biol Chem. 2005 Nov 4;280(44):36541-4. doi: 10.1074/jbc.C500243200. Epub 2005 Aug 22. PMID: 16115897.
[3]. Cheng B, Wang Q, et,al.MIF inhibitor, ISO-1, attenuates human pancreatic cancer cell proliferation, migration and invasion in vitro, and suppresses xenograft tumour growth in vivo. Sci Rep. 2020 Apr 21;10(1):6741. doi: 10.1038/s41598-020-63778-y. PMID: 32317702; PMCID: PMC7174354.
[4]. Liu Y, Liu Y, et,al. MIF inhibitor ISO-1 alleviates severe acute pancreatitis-associated acute kidney injury by suppressing the NLRP3 inflammasome signaling pathway. Int Immunopharmacol. 2021 Jul;96:107555. doi: 10.1016/j.intimp.2021.107555. Epub 2021 Apr 3. PMID: 33823428.
[5]. Wang B, Zhao K, et,al. Protective Mechanism of MIF Inhibitor ISO-1 on Intrahepatic Bile Duct Cells in Rats with Severe Acute Pancreatitis. Dig Dis Sci. 2021 Oct;66(10):3415-3426. doi: 10.1007/s10620-020-06674-9. Epub 2020 Oct 29. PMID: 33123939.
[6]. West PW, Parker LC, et,al. Differential and cell-type specific regulation of responses to Toll-like receptor agonists by ISO-1. Immunology. 2008 Sep;125(1):101-10. doi: 10.1111/j.1365-2567.2008.02825.x. Epub 2008 Mar 18. PMID: 18355244; PMCID: PMC2526264.
[7]. Ohkawara T, Okubo N, et,al. Protective effect of ISO-1 with inhibition of RIPK3 up-regulation and neutrophilic accumulation on acetaminophen-induced liver injury in mice. Toxicol Lett. 2021 Mar 15;339:51-59. doi: 10.1016/j.toxlet.2020.12.015. Epub 2020 Dec 25. PMID: 33370591.