Article
Agriculture, Dairy & Animal Science
Guoyan Wang, Jun Zhang, Shengru Wu, Senlin Qin, Yining Zheng, Chao Xia, Huijun Geng, Junhu Yao, Lu Deng
Summary: Cattle have a unique mechanism for efficient hepatic gluconeogenesis, involving the high expression of specific genes and the activation of the mTORC1 signaling pathway. These findings are important for understanding the mechanism underlying the quantitative differences in hepatic gluconeogenesis efficiency between cattle and non-ruminant animals.
Review
Pharmacology & Pharmacy
Ya-Na Yang, Mao-Qing Zhang, Feng-Lin Yu, Bing Han, Ming-Yue Bao, Xing Li, Yuan Zhang
Summary: Neurodegenerative disorders (NDDs) are characterized by progressive loss of vulnerable neuronal populations and myelin sheath, leading to behavioral and cognitive dysfunction. Peroxisome proliferator-activated receptor-? coactivator-1a (PGC-1a) has shown a strong connection with NDDs and its understanding is important for the development of therapeutic strategies. This review provides an overview of PGC-1a, its role in various NDDs, and the mechanisms through which it exerts neuroprotective effects.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Yanhao Qiu, Mailin Gan, Xingyu Wang, Tianci Liao, Qiuyang Chen, Yuhang Lei, Lei Chen, Jinyong Wang, Ye Zhao, Lili Niu, Yan Wang, Shunhua Zhang, Li Zhu, Linyuan Shen
Summary: Excessive expansion of adipocytes can lead to ectopic fat deposition, increasing the risk of metabolic diseases. Peroxisome proliferator-activated receptor gamma (PPARγ) plays a crucial role in fat cell differentiation and adipogenesis.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Pharmacology & Pharmacy
Chang Wang, Fei Peng, Bohua Zhong, Ying Shi, Xiaomei Wang, Xueyuan Jin, Junqi Niu
Summary: The study showed that MBT1805 has therapeutic effects on ANIT-induced cholestasis, improving abnormal biochemical indicators, gallbladder enlargement, and histopathological changes. By regulating bile acid synthesis, biotransformation, and transport, MBT1805 helps relieve cholestasis.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ye Liu, Yan Duan, Nan Zhao, Xinxin Zhu, Xiaoting Yu, Shiyu Jiao, Yanting Song, Li Shi, Yutao Ma, Xia Wang, Baoqi Yu, Aijuan Qu
Summary: The study reveals that PPAR alpha plays a critical protective role in Ang II-induced hypertension by attenuating ROS production in VSMCs, providing a potential therapeutic target for hypertensive diseases.
Review
Oncology
Wei-Yi Huang, Peng-Ming Sun
Summary: ERRα and PPARγ are two nuclear receptors that play important roles in human physiological functions through regulating gene transcription and ligand-dependent mechanisms, respectively. They are both associated with energy metabolism and tumorigenesis.
MOLECULAR MEDICINE REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Mahesha Gangadhariah, Triveni Pardhi, Jahnavi Ravilla, Subhash Chandra, Sridevi Annapurna Singh
Summary: PPAR gamma agonists are effective in treating type 2 diabetes but have severe side effects. Lemon contains eriocitrin, which may have potential as a PPAR gamma agonist.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Neurosciences
Riham M. Mansour, Nesrine S. El Sayed, Maha A. E. Ahmed, Ayman E. El-Sahar
Summary: This study aimed to explore the neuroprotective effect of telmisartan in 3-nitropropionic acid-induced neurotoxicity. The results showed that telmisartan improved motor and cognitive functioning, reduced neuronal inflammation and apoptosis, and promoted mitochondrial biogenesis through PPAR gamma activation.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Immunology
Xiaohua Wu, Bei Cheng, Xiaojuan Guo, Qinqin Wu, Shan Sun, Ping He
Summary: The biochemical mechanisms of Chlamydia pneumoniae (Cpn)-induced foam cell formation in early atherosclerosis involve upregulation of SR-A1 and ACAT1, as well as downregulation of ABCA1/G1 expression by both PPAR alpha and PPAR gamma pathways.
MICROBIAL PATHOGENESIS
(2021)
Review
Cell Biology
Iason Psilopatis, Kleio Vrettou, Florian Nima Fleckenstein, Stamatios Theocharis
Summary: Preeclampsia is a common hypertensive disorder in pregnancy, and PPARs play a significant role in its pathophysiology. Studies have shown contradictory conclusions regarding PPAR expression in preeclamptic placentae, but PPAR gamma agonists have been identified as a novel and potent anti-preeclamptic treatment option.
Review
Biochemistry & Molecular Biology
Iason Psilopatis, Kleio Vrettou, Constantinos Troungos, Stamatios Theocharis
Summary: Endometrial carcinoma is the most common malignant tumor of the female genital tract in the United States. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptor proteins which regulate gene expression. In our literature review of 27 relevant studies published between 2000 and 2023, it was found that PPAR alpha and PPAR beta/delta isoforms were upregulated in endometrial cancer cells, while PPAR gamma levels were significantly lower. Interestingly, PPAR agonists were found to be potent anti-cancer therapeutic alternatives. Overall, PPARs seem to play a significant role in endometrial cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Xin-xin Zhu, Xia Wang, Shi-yu Jiao, Ye Liu, Li Shi, Qing Xu, Jing-jing Wang, Yun-er Chen, Qi Zhang, Yan-ting Song, Ming Wei, Bao-qi Yu, Jens Fielitz, Frank J. Gonzalez, Jie Du, Ai-juan Qu
Summary: Cardiac dysfunction is a key component in sepsis-induced multi-organ failure. The peroxisome proliferator-activated receptor (PPAR) signaling pathway, especially PPARa, is significantly decreased in septic cardiomyopathy. Cardiomyocyte-specific PPARa deficiency exacerbates mitochondrial dysfunction and fatty acid metabolism impairment, leading to cardiac dysfunction. Targeting PPARa may be a therapeutic strategy for the treatment of septic cardiomyopathy.
ACTA PHARMACOLOGICA SINICA
(2023)
Review
Pharmacology & Pharmacy
Lara Senn, Anna-Maria Costa, Rossella Avallone, Katarzyna Socala, Piotr Wlaz, Giuseppe Biagini
Summary: The peroxisome proliferator-activated receptor gamma (PPAR gamma), known for its role in metabolic disorders, has been increasingly investigated for its potential involvement in neurological diseases, particularly in epilepsy. Epilepsy, a chronic neurological disorder, has a significant impact on patients' psychological, social, and economic well-being. With a global prevalence of 0.5%-1.0%, epilepsy ranks fourth in importance among neurological disorders. This review focuses on recent findings regarding the intracellular processes dependent on PPAR gamma and their potential anti-seizure effects, as well as promising results from clinical investigations involving PPAR gamma agonists and the ketogenic diet in epilepsy rodent models.
PHARMACOLOGY & THERAPEUTICS
(2023)
Review
Biochemistry & Molecular Biology
Hiroyuki Miyachi
Summary: Recent progress in understanding the structure and pharmacology of hPPAR gamma has allowed for investigation of various ligands and their effects on biological responses. These ligands serve as valuable tools for studying hPPAR gamma function and potential drugs for hPPAR gamma-related diseases. This review summarizes the medicinal chemistry research on the design, synthesis, and evaluation of hPPAR gamma antagonists based on the induction/inhibition concept of helix 12 (H12) and presents X-ray crystallographic analyses of their unique binding modes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Fisheries
Xiang-Yu Wu, Li Nie, Xin-Jiang Lu, Chen-Jie Fei, Jiong Chen
Summary: In this study, the role of PPAR gamma in immune regulation in teleost fish was investigated. Results showed that the expression of LcPPAR gamma changed during infection and DHA treatment, and was associated with the expression of immune-related genes.
FISH & SHELLFISH IMMUNOLOGY
(2022)
Article
Chemistry, Organic
Thanh-Hao Huynh, Gene-Hsiang Lee, Junichi Tanaka, Hsing-Pang Hsieh, Lun Kelvin Tsou, Mingzi M. Zhang, Tsu-Jen Kuo, Zhi-Hong Wen, Chung-Kuang Lu, Ping-Jyun Sung
Summary: Six chlorine-containing briarane analogues, including two new compounds, briarenols U (1) and V (2), and four known metabolites were isolated from an octocoral identified as Briareum stechei. The structures of compounds 1-6 were elucidated using spectroscopic methods, with the stereochemistry of solenolide B (3) being revised. Briarane 1 was found to induce significant in vitro inflammatory activity in LPS-induced RAW264.7 macrophage cells.
TETRAHEDRON LETTERS
(2021)
Article
Chemistry, Multidisciplinary
M. Ramya Chandar Charles, Mu-Chun Li, Hsing-Pang Hsieh, Mohane Selvaraj Coumar
Summary: The study explores a novel inhibitor design strategy for G9a protein methyltransferase, showing that incorporating a guanidine group in the inhibitor can improve its potency and binding affinity towards G9a.
Article
Chemistry, Medicinal
Ya-Hui Chi, Teng-Kuang Yeh, Yi-Yu Ke, Wen-Hsing Lin, Chia-Hua Tsai, Wan-Ping Wang, Yen-Ting Chen, Yu-Chieh Su, Pei-Chen Wang, Yan-Fu Chen, Zhong-Wei Wu, Jen-Yu Yeh, Ming-Chun Hung, Mine-Hsine Wu, Jing-Ya Wang, Ching-Ping Chen, Jen-Shin Song, Chuan Shih, Chiung-Tong Chen, Chun-Ping Chang
Summary: The study describes the design and synthesis of pyrimidine-based derivatives that can inhibit Aurora A kinase activity and reduce levels of MYC-family oncoproteins. Compound 25, resulting from pharmacokinetic optimization, demonstrated oral bioavailability and effectively reduced cMYC protein levels, showing potential for treatment of MYC-amplified cancers.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Chiung-Yi Huang, Shu-Yu Lin, Tsu-An Hsu, Hsing-Pang Hsieh, Ming-Hsi Huang
Summary: This study investigates the use of AB-type diblock copolymers PEG-PLA for dispersing the chemotherapeutic agent DBPR114 and demonstrates its potential for cancer therapy. In vitro experiments show that replacing DMSO with PEG-PLA polymeric micelles can maintain the anti-proliferative effect of DBPR114 on leukemia cell lines. Furthermore, in vivo experiments in tumor-bearing mice indicate that co-delivery of antitumor drug and antigen agents can synergistically enhance the efficacy of cancer therapy.
Article
Chemistry, Medicinal
Mu-Chun Li, Wen-Hsing Lin, Pei-Chen Wang, Yu-Chieh Su, Pei-Yi Chen, Chu-Min Fan, Ching-Ping Chen, Chen-Lung Huang, Chun-Hsien Chiu, Ling Chang, Chiung-Tong Chen, Teng-Kuang Yeh, Hsing-Pang Hsieh
Summary: The rare oncogenic NTRK gene fusions result in uncontrolled TRK signaling, leading to various solid tumors in adults and children. Compound 39, designed and synthesized based on the architecture of the multi-targeted clinical candidate BPR1K871, showed high selectivity for TRKA, potent cellular activity, good oral bioavailability, and in vivo efficacy in a xenograft model, making it a promising next-generation, selective, orally-administered type II TRK inhibitor.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Kun-Hung Lee, Wan-Ching Yen, Wen-Hsing Lin, Pei-Chen Wang, You-Liang Lai, Yu-Chieh Su, Chun-Yu Chang, Cai-Syuan Wu, Yu-Chen Huang, Chen-Ming Yang, Ling-Hui Chou, Teng-Kuang Yeh, Chiung-Tong Chen, Chuan Shih, Hsing-Pang Hsieh
Summary: The study describes the discovery of orally active and selective CSF1R inhibitors, demonstrating their potent anti-tumor effects through in vivo experiments. By utilizing molecular docking and structural studies, the researchers were able to enhance the potency of the inhibitors and alter the tumor microenvironment to increase the M1/M2 ratio.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Richard Kuan-Lin Lee, Tian-Neng Li, Sui-Yuan Chang, Tai-Ling Chao, Chun-Hsien Kuo, Max Yu-Chen Pan, Yu-Ting Chiou, Kuan-Ju Liao, Yi Yang, Yi-Hsuan Wu, Chen-Hao Huang, Hsueh-Fen Juan, Hsing-Pang Hsieh, Lily Hui-Ching Wang
Summary: This study developed a new method to detect the molecular interaction between the receptor-binding domain (RBD) of SARS-CoV-2 and the ACE2 receptor, and identified two drugs, Etravirine and Dolutegravir, as effective entry inhibitors against SARS-CoV-2. These drugs showed similar neutralizing activities against different variants of the virus.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Chemistry, Multidisciplinary
Chih-Ming Chen, Hsing-Pang Hsieh
Summary: The Diels-Alder adducts of masked ortho-benzoquinone (MOB) exhibit high regio- and stereoselectivity and can be formed under mild conditions. MOB has various functional groups, is easily accessible, and can be used for complex structure construction through chemical transformations. Therefore, MOB is considered an important intermediate for total synthesis of natural products.
JOURNAL OF THE CHINESE CHEMICAL SOCIETY
(2022)
Article
Chemistry, Medicinal
Mu-Chun Li, Mohane Selvaraj Coumar, Shu-Yu Lin, Yih-Shyan Lin, Guan-Lin Huang, Chun-Hwa Chen, Tzu-Wen Lien, Yi-Wen Wu, Yen-Ting Chen, Ching-Ping Chen, Yu-Chen Huang, Kai-Chia Yeh, Chen-Ming Yang, Bikashita Kalita, Shiow-Lin Pan, Tsu-An Hsu, Teng-Kuang Yeh, Chiung-Tong Chen, Hsing-Pang Hsieh
Summary: The development of orally bioavailable, furanopyrimidine-based double-mutant (L858R/T790M) EGFR inhibitors is discussed. The selectivity for mutant EGFR was achieved by replacing the (S)-2-phenylglycinol moiety with either an ethanol or an alkyl substituent. The optimized lead compound 52 displayed selective inhibition of cancer cells overexpressing EGFRL858R/T790M and showed in vivo antitumor effects in mouse xenograft models.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Ying-Ting Hsu, Shen-Ren Chen, Yung-Chiao Chang, Hsiao-Fu Chang, Teng-Kuang Yeh, Jian-Ying Chuang, Horace H. Loh, Hsing-Pang Hsieh, Shau-Hua Ueng, Shiu-Hwa Yeh
Summary: The demand for a non-addictive analgesic medication is increasing due to clinical misuse. Compound 14 is a dual agonist of the mu opioid receptor (MOR) and nociceptin-orphanin FQ opioid peptide (NOP) receptor, providing pain relief at very small doses and reducing unwanted side effects. Evaluating its effects in wild type and humanized mice can help develop a safer prescription analgesic drug.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Chih-Ming Chen, Sheng-Kuo Lin, Chi-Tien Hsieh, Julakanti Satyanarayana Reddy, Yi Ning Teoh, Mu-Jeng Cheng, Hsing-Pang Hsieh
Summary: An acyl radical reaction of bicyclo[2.2.2]octenone is described, which can yield rearranged or cyclized isotwistane products. The influence of ring strain on the reaction was demonstrated. DFT calculations showed that the reaction is under thermodynamic control and proceeds via a 5-exo-trig cyclization intermediate, which can undergo either hydrogen-atom transfer to give a cyclized product or rearrangement via a twistane intermediate to give a rearranged product.
Article
Chemistry, Medicinal
Mu -Chun Li, Mohane Selvaraj Coumar, Shu-Yu Lin, Yih-Shyan Lin, Guan-Lin Huang, Chun-Hwa Chen, Tzu-Wen Lien, Yi-Wen Wu, Yen-Ting Chen, Ching-Ping Chen, Yu-Chen Huang, Kai-Chia Yeh, Chen -Ming Yang, Bikashita Kalita, Shiow-Lin Pan, Tsu-An Hsu, Teng-Kuang Yeh, Chiung-Tong Chen, Hsing-Pang Hsieh
Summary: This article describes the development of orally bioavailable, furanopyrimidine-based double-mutant (L858R/T790M) EGFR inhibitors. Selectivity for mutant EGFR was achieved by replacing the (S)-2-phenylglycinol moiety of compound 12 with either an ethanol or an alkyl substituent. The lead compound 52 showed 8-fold selectively inhibition of H1975 (EGFR(L858R/T790M) overexpressing) cancer cells and displayed in vivo antitumor effects in two mouse xenograft models with TGI = 74.9% and 97.5% after oral administration (F = 27%).
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Cell Biology
Monika Kumari, Ruei-Min Lu, Mu-Chun Li, Jhih-Liang Huang, Fu-Fei Hsu, Shih-Han Ko, Feng-Yi Ke, Shih-Chieh Su, Kang-Hao Liang, Joyce Pei-Yi Yuan, Hsiao-Ling Chiang, Cheng-Pu Sun, I-Jung Lee, Wen-Shan Li, Hsing-Pang Hsieh, Mi-Hua Tao, Han-Chung Wu
Summary: The COVID-19 pandemic continues to be a global health crisis, and while vaccines and therapeutics have been developed, challenges remain in addressing the effectiveness against new variants and supporting clinical trials.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
Article
Cell Biology
Jai-Shin Liu, Wei-Kai Fang, Shan-Min Yang, Meng-Chen Wu, Tsan-Jan Chen, Chih-Ming Chen, Tung-Yueh Lin, Kai-Lun Liu, Chien-Ming Wu, Yun-Ching Chen, Chih-Pin Chuu, Ling-Yu Wang, Hsing-Pang Hsieh, Hsing-Jien Kung, Wen-Ching Wang
Summary: Myricetin, identified as a potent alpha-ketoglutarate-type inhibitor, blocks the demethylation activity by KDM4s and reduces the proliferation of both androgen-dependent and androgen-independent CRPC cells. A synergistic cytotoxic effect is observed for the combination of myricetin and enzalutamide on CRPC cells. PLGA-encapsulated myricetin in combination with enzalutamide shows significant antitumor activity in a CRPC xenograft model, suggesting its potential effectiveness for CRPC.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
Article
Cell Biology
You-Liang Lai, Kai-Hung Wang, Hsing-Pang Hsieh, Wan-Ching Yen
Summary: DBPR114 showed activity against HCC tumor cell proliferation in vitro regardless of p53 alteration status and tumor grade. It induced growth inhibition in HCC cells through apoptosis induction, cell cycle arrest, and polyploidy formation. DBPR114 also exhibited anti-angiogenic effects and significantly inhibited tumor growth in multiple HCC tumor xenograft models.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)