Review
Biochemistry & Molecular Biology
Lulin Ma, Wenjing Zhao, Shiqian Huang, Feng Xu, Yafeng Wang, Daling Deng, Tianhao Zhang, Shaofang Shu, Xiangdong Chen
Summary: Pain, an important problem in medicine and public health, has significant research significance. Opioids are currently the main drugs used to relieve pain, but their use is limited due to obvious side effects. Therefore, there is an urgent need to develop new drugs for pain relief. Multiple studies have shown that the IGF/IGF-1R pathway plays a crucial role in the occurrence and development of pain. This review summarizes and discusses the therapeutic potential of the IGF/IGF-1R signal pathway for pain. It also highlights the regulation of pain by IGF/IGF-1R through actions on neuronal excitability, neuroinflammation, glial cells, apoptosis, and more. However, further research is still needed to fully understand the mechanisms of pain occurrence and development. In conclusion, while more in-depth studies are required, these findings suggest that the IGF/IGF-1R signal pathway holds promise as a therapeutic target for pain.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Review
Oncology
Upendra K. Soni, Liam Jenny, Rashmi S. Hegde
Summary: The insulin-like growth factor receptor (IGF-1R) has been extensively studied as a potential target in oncology, but the initial promise has not been fulfilled due to resistance mechanisms and toxicities. Lack of patient stratification based on biomarkers in previous clinical trials has been recognized as a limitation. There is now growing interest in revisiting IGF-1R targeted therapeutics with predictive biomarker-driven patient stratification. The sub-cellular localization of IGF-1R has emerged as a potential biomarker.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Cell Biology
Yu-Tzu Chan, Ruey-Jen Lin, Ya-Hui Wang, Tsai-Hsien Hung, Yenlin Huang, John Yu, Jyh-Cherng Yu, Alice L. Yu
Summary: This study reveals the crucial role of YAP in breast cancer stem cells. Knockdown of YAP reduces the viability and stemness of BCSCs in vitro and tumor formation in vivo. IGF-1R and IGF-1 regulate the expression and localization of YAP, and YAP overexpression increases the expression of IGF-1. Clinical analysis shows that high levels of YAP and IGF-1 are associated with shorter overall survival in basal-like breast cancer patients. In conclusion, the interplay between YAP and the IGF-1/IGF-1R pathway is clinically relevant for sustaining the properties of BCSCs.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Oncology
Yinqi Zhang, Chengqi Gao, Fei Cao, Ying Wu, Shuanggang Chen, Xue Han, Jingqin Mo, Zhiyu Qiu, Weijun Fan, Penghui Zhou, Lujun Shen
Summary: IGF-1 and IGF-1R show inconsistent gene expression levels in various cancer cell lines, with high expression typically detected in most malignant tumors. High expression of IGF-1 is closely associated with unfavorable overall survival in BLCA, CHOL, and LAML patients, while high expression of IGF-1R is closely linked to poor overall survival in BLCA, LIHC, and LUAD patients.
FRONTIERS IN ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Panpan Wang, Victor C. Y. Mak, Lydia W. T. Cheung
Summary: The insulin-like growth factor (IGF) axis plays important roles in cancer development and metastasis. The type 1 IGF receptor (IGF-1R) is a key member in the IGF axis and has been recognized for its oncogenic role in multiple cancer lineages. This article reviews the occurrence of IGF-1R aberrations and activation mechanisms in cancers, and discusses the available therapeutic agents for IGF-1R inhibition, including antisense oligonucleotide, tyrosine kinase inhibitors, and monoclonal antibodies. Combination therapy targeting IGF-1R and other oncogenic vulnerabilities has shown promise, and new concepts such as blockage of nuclear translocation of IGF-1R are being explored to improve therapeutic efficacy.
Article
Cell Biology
Maria Dobre, Vlad Herlea, Catalina Vladut, Mihai Ciocirlan, Vasile Daniel Balaban, Gabriel Constantinescu, Mircea Diculescu, Elena Milanesi
Summary: The study identified a panel of downregulated miRNAs in PDAC tissue, which could serve as potential therapeutic targets for the development of new miRNA-based therapies for PDAC.
Article
Cell Biology
Ming Xiu, Xia Huan, Yang Ou, Sha Ying, Jianmeng Wang
Summary: The study investigated the cellular behavior and characteristics of IGF-1/IGF-1R in intestinal cells, revealing that IGF-1 can internalize into the cytoplasm and transport into the cell nuclei. It was found that IGF-1R undergoes clathrin-mediated endocytosis and enters into Rab-5-positive endosomes before being transported to the cell nuclei along microtubules, promoting cell proliferation.
CELL PROLIFERATION
(2021)
Article
Cell Biology
Xinyu Wang, Pengcheng Zhou, Liangxin Lin, Bo Wu, Zhaoyu Fu, Xing Huang, Dong Zhu
Summary: IGF-1R inhibitors have been identified as a promising drug target for Ewing sarcoma. In this study, compounds capable of inhibiting IGF-1R function were screened using virtual technology. Two potential inhibitors, ZINC000014946303 and ZINC000006003042, were found with high binding affinity to IGF-1R. These compounds showed good toxicity profiles and could serve as a direction for future IGF-1R inhibitor development.
Review
Biochemistry & Molecular Biology
Syuan-Ling Lin, Chih-Yang Lin, Wei Lee, Chiao-Fang Teng, Woei-Cherng Shyu, Long-Bin Jeng
Summary: This review focuses on the role of IGF/IGF-1R signaling in cancer initiation and proliferation, maintenance of stem cell characteristics, and enhancement of stem cell-based therapeutics. It summarizes the current progress in preclinical IGF-targeted therapies and the function of IGF/IGF-1R signaling in stem cell self-renewal and regenerative medicine.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Yongsheng Liu, Shengze Yu, Tianqi Xu, Vitalina Bodenko, Anna Orlova, Maryam Oroujeni, Sara S. Rinne, Vladimir Tolmachev, Anzhelika Vorobyeva, Torbjorn Graslund
Summary: This study evaluated the use of Ga-68 and In-111-labeled affibody construct NODAGA-(HE)(3)-Z(IGF-1R:4551) for the imaging of IGF-1R expression using PET and SPECT techniques. The results showed that these imaging probes could specifically bind to IGF-1R both in vitro and in vivo, demonstrating their potential for visualizing IGF-1R expression in malignant tumors.
Article
Cell Biology
Zhang Weiwei, Xie Ya, Wang Wenwen, Jia Jia, Bai Jing, Zhang Ruitao, Wang Chunfang, Guo Ruixia
Summary: Ovarian cancer, the deadliest gynecological malignant tumor, is closely related to IGF-1R. The novel anti-idiotypic antibody B003-2A can inhibit IGF-1R signaling and proliferation of ovarian cancer cells, as well as enhance cisplatin sensitivity, showing potential for ovarian cancer treatment and IGF-1R antagonist development.
Article
Oncology
Han Koo, Sangwon Byun, Jieun Seo, Yuri Jung, Dong Chul Lee, Jung Hee Cho, Young Soo Park, Young Il Yeom, Kyung Chan Park
Summary: IGF-1R is commonly overexpressed in solid tumors, but gene amplification is rare. Research shows that PKM2 regulates IGF-1R protein expression by stabilizing the precursor protein through HSP90 binding. Inhibiting PKM2 reduces IGF-1R levels, inhibits AKT activation, and increases apoptotic cell death, suggesting PKM2 as a potential therapeutic target in cancers with dysregulated IGF signaling.
Article
Biochemistry & Molecular Biology
Ying Tang, Mengchun Zhou, Rongrong Huang, Ling Shen, Li Yang, Zhongqiu Zhou, Hui Ren, Ying Bai
Summary: The study demonstrates that HECTD1 is upregulated in primary mouse astrocytes after LPS treatment. Knockdown of HECTD1 inhibits LPS-induced astrocyte activation in vitro and in vivo, while overexpression of HECTD1 promotes LPS-induced astrocyte activation.
CELL AND BIOSCIENCE
(2021)
Article
Anatomy & Morphology
Cemile Merve Seymen, Atiye Seda Yar Saglam, Zubeyir Elmazoglu, Gokce Nur Arik, Gulnur Take Kaplanoglu
Summary: The study investigated the involvement of endometrial IGF-1R/IGF-1/Bcl-2 pathways and the potential regulatory effects of exogenously administered melatonin in PCOS. Results showed that melatonin administration could reverse the morphological changes induced by polycystic ovary induction.
Article
Agriculture, Dairy & Animal Science
Junyan Bai, Xinle Wang, Jingyun Li, Longwei Wang, Hongdeng Fan, Mengke Chen, Fanlin Zeng, Xiaoning Lu, Yuhan He
Summary: This study investigated the association between single nucleotide polymorphisms (SNPs) of the IGF-1R gene and egg quality and carcass traits in quails. Two SNPs (A57G and A72T) were found in three quail strains, with A57G associated with yolk width in one strain and A72T associated with egg shell thickness and other egg traits in different strains. Haplotypes based on the two SNPs also had significant effects on egg shell thickness and egg weight in the quail strains. Additionally, A72T was associated with liver weight and dressing percentage in all three strains. The IGF-1R gene may serve as a molecular genetic marker for improving egg quality and carcass traits in quails.
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)