9VGT
Crystal structure of Peroxiredoxin I in complex with compound 19-150
This is a non-PDB format compatible entry.
Summary for 9VGT
| Entry DOI | 10.2210/pdb9vgt/pdb |
| Descriptor | Peroxiredoxin-1, methyl (2~{S})-2-[[(2~{R},4~{a}~{S},6~{a}~{S},6~{a}~{R},13~{S},14~{a}~{S},14~{b}~{R})-13-bromanyl-2,4~{a},6~{a},6~{a},9,14~{a}-hexamethyl-10-oxidanyl-11-oxidanylidene-1,3,4,5,6,13,14,14~{b}-octahydropicen-2-yl]carbamoylamino]propanoate (3 entities in total) |
| Functional Keywords | prdx1, inhibitor, complex, oxidoreductase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 2 |
| Total formula weight | 39303.76 |
| Authors | |
| Primary citation | Li, M.Y.,Li, Y.,Wang, X.,Shang, F.F.,Long, Y.,Li, Y.L.,Wang, Z.,Zhang, A.,Zhang, H.,Ding, C.,Sun, Z. Synthesis and pharmacological evaluation of brominated derivatives of natural product celastrol for treatment of hepatic fibrosis. Eur.J.Med.Chem., 309:118765-118765, 2026 Cited by PubMed Abstract: Effective therapeutic agents against hepatic fibrosis remain scarce. Natural product Celastrol has demonstrated promising anti-hepatic fibrosis activity. However, further clinical development is impaired by its toxicity. We performed a bromination modification at the C-ring, an unexplored moiety of Celastrol, leading to a series of brominated derivatives. Among them, derivative 5 effectively suppressed various stimulus-induced activation of NLRP3 inflammasome to block the activation of HSCs, thus reducing the collagen deposition. Meanwhile, 5 was identified as a covalent PRDX1 inhibitor with high isoform selectivity, which accelerated ROS accumulation to induce apoptosis of the activated HSCs. Derivative 5 at a dose of 20 mg/kg exhibited superior safety profile with no significant weight loss or hepatotoxicity. At 1 mg/kg, it significantly ameliorates CCl-induced hepatic damage and fibrosis in mice. Taken together, our work provided a novel brominated derivative of Celastrol as promising lead compound against hepatic fibrosis. PubMed: 41844113DOI: 10.1016/j.ejmech.2026.118765 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.79 Å) |
Structure validation
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