8YG7

HSA Copper Indomethacin Complex

This is a non-PDB format compatible entry.

Summary for 8YG7

• Entry DOI: 10.2210/pdb8yg7/pdb
• Descriptor: Albumin, chlorido{N,N-dimethyl-N'-[2-methyl-1-(pyridin-2-yl-kappaN)propylidene]carbamohydrazonothioato-kappa~2~N',S}copper(2+), INDOMETHACIN, ... (5 entities in total)
• Functional Keywords: complex, protein binding
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 136919.06

Authors

Zhang, Z.L.,Yang, F. (deposition date: 2024-02-26, release date: 2025-03-12, Last modification date: 2026-08-12)

Primary citation

Man, X.,Li, S.,Xu, G.,Li, W.,Zhu, M.,Zhang, Z.,Liang, H.,Yang, F.
Developing a Copper(II) Isopropyl 2-Pyridyl Ketone Thiosemicarbazone Compound Based on the IB Subdomain of Human Serum Albumin-Indomethacin Complex: Inhibiting Tumor Growth by Remodeling the Tumor Microenvironment.
J.Med.Chem., 67:5744-5757, 2024

PubMed Abstract: To develop a next-generation metal agent and dual-agent multitargeted combination therapy, we developed a copper (Cu) compound based on the properties of the human serum albumin (HSA)-indomethacin (IND) complex to remodel the tumor microenvironment (TME). We optimized a series of Cu(II) isopropyl 2-pyridyl ketone thiosemicarbazone compounds to obtain a Cu(II) compound (C4) with significant cytotoxicity and then constructed an HSA-IND-C4 complex (HSA-IND-C4) delivery system. IND and C4 bind to the hydrophobic cavities of the IB and IIA domains of HSA, respectively. , the HSA-IND-C4 not only showed enhanced antitumor efficacy relative to C4 and C4 + IND but also improved their targeting ability and decreased their side effects. The antitumor mechanism of C4 + IND involved acting on the different components of the TME. IND inhibited tumor-related inflammation, while C4 not only induced apoptosis and autophagy of cancer cells but also inhibited tumor angiogenesis.

PubMed: 38553427
DOI: 10.1021/acs.jmedchem.3c02378

Experimental method

X-RAY DIFFRACTION (2.09 Å)