9BNQ
N-(4-(isothiocyanatomethyl)phenyl)methanesulfonamide complexed with Macrophage Migration Inhibitory Factor
これはPDB形式変換不可エントリーです。
9BNQ の概要
エントリーDOI | 10.2210/pdb9bnq/pdb |
分子名称 | Macrophage migration inhibitory factor, N-{[4-(methanesulfonamido)phenyl]methyl}methanethioamide, SULFATE ION, ... (5 entities in total) |
機能のキーワード | cytokine, tautomerase, isomerase, isothiocyanate, isomerase inhibitor complex |
由来する生物種 | Homo sapiens (human) |
タンパク質・核酸の鎖数 | 3 |
化学式量合計 | 38398.68 |
構造登録者 | Fellner, M.,Rutledge, M.T.,Putha, L.,Kok, L.K.,Gamble, A.B.,Wilbanks, S.M.,Vernall, A.J.,Tyndall, J.D.A. (登録日: 2024-05-02, 公開日: 2024-07-24, 最終更新日: 2024-11-20) |
主引用文献 | Putha, L.,Kok, L.K.,Fellner, M.,Rutledge, M.T.,Gamble, A.B.,Wilbanks, S.M.,Vernall, A.J.,Tyndall, J.D.A. Covalent Isothiocyanate Inhibitors of Macrophage Migration Inhibitory Factor as Potential Colorectal Cancer Treatments. Chemmedchem, 19:e202400394-e202400394, 2024 Cited by PubMed Abstract: Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with roles in innate and adaptive human immune responses, as well as inflammation. MIF exerts its biological activity by binding to the cell surface receptor CD74 as well as intracellular signalling proteins. MIF also possesses keto-enol tautomerase activity. Inhibition of the tautomerase activity has been associated with loss of biological activity of MIF and a potential anticancer target. Isothiocyanates (ITCs) are a class of compounds present in cruciferous vegetables that inhibit the MIF tautomerase activity via covalent modification of the N-terminal proline. A range of substituted ITCs featuring benzyl, phenethyl and phenyl propyl isothiocyanates were designed, synthesised and tested to determine any structure activity relationship for inhibiting MIF. Crystal structures of covalent compounds 8 and 9 in complex with rhMIF revealed key hydrogen bonding and edge-to-face π stacking interactions. Compound 9 and 11 with sub micromolar activity were tested in the NCI60 cancer cell lines panel. Both compounds showed tissue-specific reduced growth in colon and renal cancer cell lines, while one of these showed potent, dose-dependent inhibition of growth against all seven colon cancer cell lines (GI50 < 2.5 µM) and all eight renal cancer cell lines (GI50 < 2.2 µM). PubMed: 38977403DOI: 10.1002/cmdc.202400394 主引用文献が同じPDBエントリー |
実験手法 | X-RAY DIFFRACTION (1.09 Å) |
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