Article
Biochemistry & Molecular Biology
Qi-Yin Chen, Ranjala Ratnayake, Rafael Hortiguela, Gustavo M. Seabra, Michael D. Cameron, J. Fernando Diaz, Maria Angela Oliva, Hendrik Luesch
Summary: Microtubules are important targets for anticancer drug discovery. Gatorbulin-1 is a new microtubule inhibitor that targets a new site at the tubulin intradimer interface. Through chemical synthesis, simplified gatorbulins were obtained and their structure-activity relationship was investigated. Some specific structural modifications were found to be functionally relevant.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Review
Immunology
Xiaoyan Zhan, Qiang Li, Guang Xu, Xiaohe Xiao, Zhaofang Bai
Summary: NLRP3 is a cytosolic pattern recognition receptor that recognizes various molecular patterns associated with pathogens and damage. Its activation leads to the assembly of the inflammasome and cleavage of IL-1 beta and IL-18. Aberrant NLRP3 activation is linked with multiple inflammatory diseases, and efforts are being made to develop inhibitors. This review summarizes the latest advances in the mechanism of NLRP3 inflammasome activation and the development of pharmacological inhibitors.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Noelle E. Gillis, Joseph R. Boyd, Jennifer A. Tomczak, Seth Frietze, Frances E. Carr
Summary: Transcriptional regulation in response to thyroid hormone is important for maintaining cellular homeostasis and identity. In this study, we used genomics to analyze TR beta and found that T-3 induces changes in genomic occupancy, chromatin accessibility, and the recruitment of chromatin remodelers. Additionally, we discovered the selective recruitment of BAF and PBAF SWI/SNF complexes to TR beta binding sites. These findings reveal the diverse modes of TR beta interaction with chromatin and the coordination of coregulator activity.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Kin H. Lau, Althea N. Waldhart, Holly Dykstra, Tracey Avequin, Ning Wu
Summary: Brown adipose tissue (BAT) has the ability to burn calories as heat, which is an attractive way to combat obesity. However, the transcriptional network resulting in the lipid synthesis to oxidation shift during thermogenesis is not completely understood.
Article
Environmental Sciences
Qi Xu, Jian Li, Shang Cao, Guangcai Ma, Xianglong Zhao, Qiuyi Wang, Xiaoxuan Wei, Haiying Yu, Zhiguo Wang
Summary: In this study, 18 OH-PBDEs with neutral and anionic forms were selected to estimate their binding interactions with the ligand binding domain (LBD) of thyroid hormone receptor O (TRO) through molecular dynamics simulations. The results indicate that most OH-PBDEs have stronger binding affinities to TRO-LBD compared to their anionic counterparts, and the hydroxyl dissociation of ligands plays a major role in their binding. Additionally, 5 hydrophobic residues (Met313, Leu330, Ile276, Leu346, and Phe272) are identified to have important contributions to binding OH-PBDEs. These findings provide a solid theoretical basis for accurately assessing the thyroid hormone disrupting effects of these chemicals.
Article
Biochemistry & Molecular Biology
Christodoula Kourtidou, Konstantinos Tziomalos
Summary: Polycystic ovary syndrome (PCOS) is a common hormonal disorder in women of reproductive age, and excess body weight worsens its symptoms. Recent studies have evaluated various pharmacological agents for managing obesity in PCOS patients, with glucagon-like peptide-1 receptor agonists showing promising results in reducing body weight. Limited data suggest that sodium-glucose cotransporter-2 inhibitors and phosphodiesterase-4 inhibitors may also be effective. This review discusses the current evidence on the safety and efficacy of these agents in overweight and obese patients with PCOS.
Article
Biochemistry & Molecular Biology
Ahmed Temirak, Jonathan G. Schlegel, Jan H. Voss, Victoria J. Vaassen, Christin Vielmuth, Tobias Claff, Christa E. Mueller
Summary: In this study, a series of irreversible A(2B)AR antagonists based on an 8-p-sulfophenylxanthine scaffold were designed and synthesized. Among them, p-(1-propylxanthin-8-yl)benzene sulfonyl fluoride (6a, PSB-21500) was identified as the most potent and selective antagonist. However, these irreversible antagonists did not interact with K269 (7.32) as previously speculated.
Article
Biochemical Research Methods
Peter Bults, Anna van der Voort, Coby Meijer, Gabe S. Sonke, Rainer Bischoff, Nico C. van de Merbel
Summary: A liquid chromatography-tandem mass spectrometry method was developed for quantifying the in vivo deamidation of biopharmaceutical proteins trastuzumab and pertuzumab. The study found significant differences between total and non-deamidated concentrations, indicating substantial deamidation in plasma. Additionally, a correlation was observed between the degree of deamidation and pharmacological activity, with deamidated trastuzumab losing its capability to inhibit the growth of breast cancer cells.
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Rashad Haidar, Frank Henkler, Josephine Kugler, Aline Rosin, Doris Genkinger, Peter Laux, Andreas Luch
Summary: This study found that the stable compartmentalization of activated AHR in the nucleus does not depend on interactions with DNA or ARNT, and ARNT does not play a role in the intracellular trafficking of AHR.
SCIENTIFIC REPORTS
(2021)
Article
Chemistry, Medicinal
Eric Breinlinger, Stacy Van Epps, Michael Friedman, Maria Argiriadi, Ellen Chien, Gekleng Chhor, Marlon Cowart, Theresa Dunstan, Candace Graff, David Hardee, J. Martin Herold, Andrew Little, Richard Mccarthy, Julie Parmentier, Matthew Perham, Wei Qiu, Michael Schrimpf, Thomas Vargo, Matthew P. Webster, Fei Wu, Dawn Bennett, Jeremy Edmunds
Summary: TYK2 is a nonreceptor tyrosine kinase that regulates autoimmune diseases. Targeting the pseudokinase domain of TYK2 allows for selective inhibition of its isoforms.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Toru Iijima, Makoto Katoh, Kei Takedomi, Yasuo Yamamoto, Hidenori Akatsuka, Naritoshi Shirata, Akito Nishi, Misae Takakuwa, Yoshinori Watanabe, Hitomi Munakata, Naomi Koyama, Tomoko Ikeda, Taku Iguchi, Harutoshi Kato, Kohei Kikkawa, Takayuki Kawaguchi
Summary: Overactivation of the mineralocorticoid receptor is involved in various diseases. A novel nonsteroidal mineralocorticoid receptor antagonist, apararenone, showed higher selectivity and stronger antihypertensive and organ-protective activity compared to the already marketed steroidal antagonist eplerenone.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Thiruventhan Karunakaran, Kok Zhuo Ngew, Ahmad Alif Danial Zailan, Vivien Yi Mian Jong, Mohamad Hafizi Abu Bakar
Summary: Mitragynine is a naturally occurring indole alkaloid extracted from the leaves of the medicinal plant Mitragyna speciosa, which shows promising analgesic effects with limited adverse effects compared to morphine. This review discusses the pharmacological and toxicological properties of mitragynine and its diastereomers, speciogynine, speciociliatine, and mitraciliatine, and explores the structure-activity relationship of these compounds.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Joerg Duschmale, Adrian Schaeublin, Erik Funder, Steffen Schmidt, Lukasz J. Kielpinski, Helle Nymark, Klaus Jensen, Troels Koch, Martina Duschmale, Erich Koller, Marianne Ravn Moller, Simone Schadt, Christophe Husser, Andreas Brink, Sabine Sewing, Tanja Minz, Jesper Wengel, Konrad Bleicher, Meiling Li
Summary: The introduction of sulfur into chemically synthesized oligonucleotides creates stereocenters on phosphorus atoms. Only recently has it become possible to synthesize fully stereodefined antisense oligonucleotides. This article describes the application of symmetrical non-bridging PS2 linkages in the context of stereodefined locked nucleic acids (LNAs) antisense oligonucleotides, aiming to reduce chiral complexity and ultimately result in single molecules.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Biochemistry & Molecular Biology
Min Wang, Li Lan, Yu-Wei Wang, Jin-Yang Zhang, Lei Shi, Li-Ping Sun
Summary: Aberrant FGF19/FGFR4 signaling is a driver of growth and survival in hepatocellular carcinoma. Selective FGFR4 inhibitors are being researched as potential drugs for targeted therapy, but none have been approved by the FDA. In this study, a series of arylurea derivatives were designed and synthesized as novel irreversible covalent FGFR4 inhibitors. Compound 6v demonstrated significant inhibition of FGFR4 phosphorylation and downstream signaling in Hep3B cells, indicating its potential for further research and optimization.
BIOORGANIC & MEDICINAL CHEMISTRY
(2023)
Article
Cell Biology
Christopher C. Pan, Raquel Maeso-Diaz, Tylor R. Lewis, Kun Xiang, Lianmei Tan, Yaosi Liang, Liuyang Wang, Fengrui Yang, Tao Yin, Calvin Wang, Kuo Du, De Huang, Seh Hoon Oh, Ergang Wang, Bryan Jian Wei Lim, Mengyang Chong, Peter B. Alexander, Xuebiao Yao, Vadim Y. Arshavsky, Qi-Jing Li, Anna Mae Diehl, Xiao-Fan Wang
Summary: Cellular senescence is a stable cell cycle arrest phenotype induced by stress, which creates a pro-inflammatory microenvironment and contributes to chronic inflammation and age-associated diseases. The molecular pathway involving thrombomodulin (THBD) signaling plays a crucial role in determining the fate of senescent cells, and inhibiting this pathway can effectively eliminate senescent cells and restore tissue homeostasis. These findings provide a potential target for developing senolytic agents to treat senescence-associated diseases.
Article
Medicine, Research & Experimental
M. S. Rashid Roni, Guanguan Li, Brandon N. Mikulsky, Daniel E. Knutson, Md Yeunus Mian, Nicolas M. Zahn, James M. Cook, Douglas C. Stafford, Leggy A. Arnold
MOLECULAR PHARMACEUTICS
(2020)
Article
Biochemistry & Molecular Biology
Olivia B. Yu, Tania R. Mutchie, Elliot S. Di Milo, Leggy A. Arnold
Article
Biochemical Research Methods
May Fern Toh, Julie M. Brooks, Tim Strassmaier, Rodolfo J. Haedo, Corey B. Puryear, Bruce L. Roth, Kosalvisal Ouk, Sokhom S. Pin
Meeting Abstract
Biochemistry & Molecular Biology
Abdelfattah Faouzi, Saheem Zaidi, Tao Che, Chad Kormos, Tiffany Zhang, Manish Madasu, Shainnel Eans, Chloe Simons, Ying-Xian Pan, Jay McLaughlin, Ivy Carroll, Ream Al Hassani, Bryan Roth, Vsevolod Katritch, Susruta Majumdar
Meeting Abstract
Biochemistry & Molecular Biology
Grant Glatfelter, Reed Stein, Hye Kang, Anthony Jones, John Irwin, Bryan Roth, Brian Shoichet, Margarita Dubocovich
Article
Multidisciplinary Sciences
David E. Gordon, Gwendolyn M. Jang, Mehdi Bouhaddou, Jiewei Xu, Kirsten Obernier, Kris M. White, Matthew J. O'Meara, Veronica V. Rezelj, Jeffrey Z. Guo, Danielle L. Swaney, Tia A. Tummino, Ruth Huttenhain, Robyn M. Kaake, Alicia L. Richards, Beril Tutuncuoglu, Helene Foussard, Jyoti Batra, Kelsey Haas, Maya Modak, Minkyu Kim, Paige Haas, Benjamin J. Polacco, Hannes Braberg, Jacqueline M. Fabius, Manon Eckhardt, Margaret Soucheray, Melanie J. Bennett, Merve Cakir, Michael J. McGregor, Qiongyu Li, Bjoern Meyer, Ferdinand Roesch, Thomas Vallet, Alice Mac Kain, Lisa Miorin, Elena Moreno, Zun Zar Chi Naing, Yuan Zhou, Shiming Peng, Ying Shi, Ziyang Zhang, Wenqi Shen, Ilsa T. Kirby, James E. Melnyk, John S. Chorba, Kevin Lou, Shizhong A. Dai, Inigo Barrio-Hernandez, Danish Memon, Claudia Hernandez-Armenta, Jiankun Lyu, Christopher J. P. Mathy, Tina Perica, Kala Bharath Pilla, Sai J. Ganesan, Daniel J. Saltzberg, Ramachandran Rakesh, Xi Liu, Sara B. Rosenthal, Lorenzo Calviello, Srivats Venkataramanan, Jose Liboy-Lugo, Yizhu Lin, Xi-Ping Huang, YongFeng Liu, Stephanie A. Wankowicz, Markus Bohn, Maliheh Safari, Fatima S. Ugur, Cassandra Koh, Nastaran Sadat Savar, Quang Dinh Tran, Djoshkun Shengjuler, Sabrina J. Fletcher, Michael C. O'Neal, Yiming Cai, Jason C. J. Chang, David J. Broadhurst, Saker Klippsten, Phillip P. Sharp, Nicole A. Wenzell, Duygu Kuzuoglu-Ozturk, Hao-Yuan Wang, Raphael Trenker, Janet M. Young, Devin A. Cavero, Joseph Hiatt, Theodore L. Roth, Ujjwal Rathore, Advait Subramanian, Julia Noack, Mathieu Hubert, Robert M. Stroud, Alan D. Frankel, Oren S. Rosenberg, Kliment A. Verba, David A. Agard, Melanie Ott, Michael Emerman, Natalia Jura, Mark von Zastrow, Eric Verdin, Alan Ashworth, Olivier Schwartz, Christophe D'Enfert, Shaeri Mukherjee, Matt Jacobson, Harmit S. Malik, Danica G. Fujimori, Trey Ideker, Charles S. Craik, Stephen N. Floor, James S. Fraser, John D. Gross, Andrej Sali, Bryan L. Roth, Davide Ruggero, Jack Taunton, Tanja Kortemme, Pedro Beltrao, Marco Vignuzzi, Adolfo Garcia-Sastre, Kevan M. Shokat, Brian K. Shoichet, Nevan J. Krogan
Article
Biochemistry & Molecular Biology
Reid H. J. Olsen, Jeffrey F. DiBerto, Justin G. English, Alexis M. Glaudin, Brian E. Krumm, Samuel T. Slocum, Tao Che, Ariana C. Gavin, John D. McCorvy, Bryan L. Roth, Ryan T. Strachan
NATURE CHEMICAL BIOLOGY
(2020)
Article
Neurosciences
Yuji Nagai, Naohisa Miyakawa, Hiroyuki Takuwa, Yukiko Hori, Kei Oyama, Bin Ji, Manami Takahashi, Xi-Ping Huang, Samuel T. Slocum, Jeffrey F. DiBerto, Yan Xiong, Takuya Urushihata, Toshiyuki Hirabayashi, Atsushi Fujimoto, Koki Mimura, Justin G. English, Jing Liu, Ken-ichi Inoue, Katsushi Kumata, Chie Seki, Maiko Ono, Masafumi Shimojo, Ming-Rong Zhang, Yutaka Tomita, Jin Nakahara, Tetsuya Suhara, Masahiko Takada, Makoto Higuchi, Jian Jin, Bryan L. Roth, Takafumi Minamimoto
NATURE NEUROSCIENCE
(2020)
Article
Chemistry, Applied
Daniel E. Knutson, M. S. Rashid Roni, Md Yeunus Mian, James M. Cook, Douglas C. Stafford, Leggy A. Arnold
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2020)
Article
Biochemistry & Molecular Biology
Xi-Ping Huang, Terrence P. Kenakin, Shuo Gu, Brian K. Shoichet, Bryan L. Roth
Article
Chemistry, Medicinal
Ho Shin Kim, Jared T. Hammill, Daniel C. Scott, Yizhe Chen, Amy L. Rice, William Pistel, Bhuvanesh Singh, Brenda A. Schulman, R. Kiplin Guy
Summary: This study has improved the pharmacokinetic performance of inhibitors targeting cullin-RING ubiquitin ligases and established the impact of the inhibitor on tumor cell growth.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Olivia B. Yu, Daniel A. Webb, Elliot S. Di Milo, Tania R. Mutchie, Kelly A. Teske, Taosheng Chen, Wenwei Lin, Carole Peluso-Iltis, Natacha Rochel, Moritz Helmstaedter, Daniel Merk, Leggy A. Arnold
Summary: The study focused on the synthesis and analysis of CTA as a VDR ligand, showing similarities in conformation and function with 1,25(OH)(2)D-3, confirming its ability to activate VDR and interact with specific genes. CTA demonstrated anti-inflammatory properties by reducing gene transcription and nitric oxide production in mouse macrophages, comparable to the effects of 1,25(OH)(2)D-3.
BIOORGANIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Heli Fan, Muhammad Asad Uz Zaman, Wenbing Chen, Taufeeque Ali, Anahit Campbell, Qi Zhang, Nurul Islam Setu, Eron Saxon, Nicolas M. Zahn, Anna M. Benko, Leggy A. Arnold, Xiaohua Peng
Summary: These two prodrugs can effectively inhibit the tumor growth of TNBC cell lines, demonstrating stronger cytotoxicity compared to traditional drugs. Pharmacokinetic properties such as drug conversion rate and half-life also influence the efficacy of the drugs.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2021)
Article
Chemistry, Organic
Kamal P. Pandey, Md Zubair Ahmed Khan, Lalit K. Golani, Prithu Mondal, Md Yeunus Mian, Farjana Rashid, V. V. N. Phani Babu Tiruveedhula, Daniel E. Knutson, Dishary Sharmin, Taukir Ahmed, Sepideh Rezvanian, Nicolas M. Zahn, Leggy A. Arnold, Jeffrey M. Witkin, James M. Cook
Article
Chemistry, Medicinal
Nicolas M. Zahn, Brandon N. Mikulsky, M. S. Rashid Roni, Gene T. Yocum, Md Yeunus Mian, Daniel E. Knutson, James M. Cook, Charles W. Emala, Douglas C. Stafford, Leggy A. Arnold
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2020)