Article
Chemistry, Multidisciplinary
Nirmalya Pradhan, Nasim Akhtar, Barnali Nath, Jorge Pena-Garcia, Anjali Gupta, Horacio Perez-Sanchez, Sachin Kumar, Debasis Manna
Summary: Quinine derivatives effectively inhibit the activity of IDO1 by competing with heme, providing a potential avenue for immunotherapy-based drug discovery strategies.
CHEMICAL COMMUNICATIONS
(2021)
Review
Oncology
Yu Yao, Heng Liang, Xin Fang, Shengnan Zhang, Zikang Xing, Lei Shi, Chunxiang Kuang, Barbara Seliger, Qing Yang
Summary: IDO1, a heme-containing enzyme, plays a crucial role in the kynurenine pathway of tryptophan metabolism, with implications in immunity and neuronal function. Despite potential applications in cancer and neurodegenerative diseases, cautionary notes from clinical trials indicate a need for better understanding of IDO1 inhibition mechanisms.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Carlos Gutierrez-Merino, Oscar H. Martinez-Costa, Maria Monsalve, Alejandro K. Samhan-Arias
Summary: Membrane cytochrome b(5) reductase is an oxidoreductase that reduces multiple acceptors localized in cellular membranes using NADH as an electron donor. The understanding of the electron transfer process of the reductase towards potential acceptors is still only partially understood. Computational analysis of protein structures provides a potential method to further investigate the roles of different domains within the reductase structure.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Tabish Iqbal, Debasis Das
Summary: The purification and biochemical characterization of plant cytochrome b5 and cytochrome b5 reductase provide important insights into their function and mechanism.
Review
Biochemistry & Molecular Biology
Leila Sawada, Antonio Carlos Rosario Vallinoto, Igor Brasil-Costa
Summary: EBV is an oncovirus associated with various types of cancer, with the reason for cancer development in only some infected individuals still unknown. EBV-associated cancers are more aggressive and resistant to treatment compared to EBV-negative cancers, making monoclonal antibodies targeting immune checkpoints a potential therapy.
Article
Biochemistry & Molecular Biology
Freeborn Rwere, Sangchoul Im, Lucy Waskell
Summary: By altering the 140s FMN binding loop of CYPOR, the activity with cyt P450s can be affected, with the mutant activity primarily determined by its ability to reduce ferric cyt P450. The different behaviors of the mutants are mainly due to the altered structure and mobility of the loop.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Chemistry, Medicinal
Rahul Singh, Deepak B. Salunke
Summary: IDO1 enzyme catalyzes the initial step of kynurenine pathway and is implicated in immune modulation, antioxidation, and cancer progression. Overexpression of IDO1 plays a pivotal role in immune evasion and cancer development. Research and development of IDO1 inhibitors holds significant potential in immunotherapy and disease treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Editorial Material
Biochemistry & Molecular Biology
F. Peter Guengerich
Summary: The paper introduces the concept of cytochrome b(5) as an auxiliary protein facilitating cytochrome P450 reactions, providing important insights for future research.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2022)
Review
Pharmacology & Pharmacy
Ana Dolsak, Stanislav Gobec, Matej Sova
Summary: This review discusses the key step of tryptophan metabolism and the importance of relevant enzymes in pathological conditions. In recent years, many inhibitors targeting these enzymes have been developed, and these inhibitors have entered clinical trials.
PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Engineering, Biomedical
Yixuan Guo, Yu Liu, Wei Wu, Daishun Ling, Qiao Zhang, Peng Zhao, Xi Hu
Summary: This article will discuss different types of IDO inhibitors and relevant clinical trials, especially feasible combined therapeutic modalities. In addition, it will also review cutting-edge nanomedicines that combine IDO inhibitors with other therapeutic modalities to effectively enhance the effectiveness of cancer therapy. Finally, the prospects of IDO inhibitors in clinical application and potential breakthroughs will be briefly discussed.
Article
Microbiology
Thiara Manuele Alves de Souza, Caroline Fernandes-Santos, Jessica Araujo da Paixao de Oliveira, Larissa Cristina Teixeira Tome, Victor Edgar Fiestas-Solorzano, Priscila Conrado Guerra Nunes, Gabriel Macedo Costa Guimaraes, Juan Camilo Sanchez-Arcila, Iury Amancio Paiva, Luis Jose de Souza, Paulo Vieira Damasco, Valber da Silva Frutuoso, Manoela Heringer, Luzia Maria De Oliveira-Pinto, Roberta Olmo Pinheiro, Flavia Barreto dos Santos, Elzinandes Leal de Azeredo
Summary: This study evaluated the activity of IDO-1 and the patterns of cytokines/chemokines in CHIKV patients. It was found that IDO-1 activity increased during the early acute phase of infection and decreased in the chronic phase. In the acute phase, concentrations of TNF-alpha, IL-6, IFN-gamma, CCL2/MCP-1, and CXCL10/IP-10 were increased. In the chronic phase, concentrations of CCL4/MIP-1 beta were increased, especially in patients with arthritis.
Article
Chemistry, Medicinal
Kai Tang, Bo Wang, Bin Yu, Hong-Min Liu
Summary: Indoleamine 2,3-dioxygenase 1 (IDO1) is an important immunosuppressive enzyme in cancer therapy. Multiple IDO1 inhibitors have entered clinical trials, and PROTAC-based degraders also show promise for cancer treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Daojing Yan, Jiakun Xu, Xiang Wang, Jiaxing Zhang, Gang Zhao, Yingwu Lin, Xiangshi Tan
Summary: This study systematically investigated the SAR405838 analogs as potential IDO inhibitors for cancer immunotherapy. The results showed that inhibitor 3 exhibited the highest IDO1 inhibitory activity among all inhibitors and demonstrated effective inhibition in MCF-7 cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Arina Kozlova, Leopold Thabault, Maxime Liberelle, Simon Klaessens, Julien R. C. Prevost, Caroline Mathieu, Luc Pilotte, Vincent Stroobant, Benoit Van den Eynde, Raphael Frederick
Summary: In this study, a new scaffold of TDO2 inhibitors, 6-(1H-indol-3-yl)-benzotriazole, was developed through rational design, leading to the synthesis of stable compounds with nanomolar cellular potency. The rigidification of the initial scaffold provided a better understanding of the structural modulations inside the active site of hTDO2.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Donghak Kim, Vitchan Kim, Yasuhiro Tateishi, F. Peter Guengerich
Summary: High-affinity binding of cytochrome b(5) (b(5)) (K-d < 100 nM) was observed with many drug-metabolizing cytochrome P450 (P450) enzymes. Evidence is provided for a ternary P450 3A4-b(5)-NADPH-P450 reductase complex, indicating the importance of ternary complexes in P450 reactions.
DRUG METABOLISM AND DISPOSITION
(2021)