8J8E

Human serum albumin-palladium(II) agent complex

Summary for 8J8E

• Entry DOI: 10.2210/pdb8j8e/pdb
• Descriptor: Serum albumin, PALMITIC ACID, ~{N},~{N}-dimethyl-7-phenyl-3-thia-1$l^{4},5,6$l^{4}-triaza-2$l^{3}-palladatricyclo[6.4.0.0^{2,6}]dodeca-1(12),4,6,8,10-pentaen-4-amine, ... (4 entities in total)
• Functional Keywords: complex, hormone
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 136999.11

Authors

Zhang, Z.L.,Zhang, J.Z. (deposition date: 2023-05-01, release date: 2024-05-01, Last modification date: 2025-08-20)

Primary citation

Li, W.,Li, S.,Zhang, Z.,Xu, G.,Man, X.,Yang, F.,Liang, H.
Developing a Multitargeted Anticancer Palladium(II) Agent Based on the His-242 Residue in the IIA Subdomain of Human Serum Albumin.
J.Med.Chem., 66:8564-8579, 2023

PubMed Abstract: To obtain next-generation metal drugs that can overcome the deficiencies of platinum (Pt) drugs and treat cancer more effectively, we proposed to develop a multitargeted palladium (Pd) agent to the tumor microenvironment (TME) based on the specific residue(s) of human serum albumin (HSA). To this end, we optimized a series of Pd(II) 2-benzoylpyridine thiosemicarbazone compounds to obtain a Pd agent (5b) with significant cytotoxicity. The HSA-5b complex structure revealed that 5b bound to the hydrophobic cavity in the HSA IIA subdomain and then His-242 replaced a leaving group (Cl) of 5b, coordinating with the Pd center. The results showed that the 5b/HSA-5b complex had significant capacity of inhibiting tumor growth, and HSA optimized the therapeutic behavior of 5b. In addition, we confirmed that the 5b/HSA-5b complex inhibited tumor growth through multiple actions on different components of TME: killing cancer cells, inhibiting tumor angiogenesis, and activating T cells.

PubMed: 37321208
DOI: 10.1021/acs.jmedchem.3c00248

Experimental method

X-RAY DIFFRACTION (2.5 Å)