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
Nikolas Hoermann, Christina Kalchschmid, Patricia Grabher, Isabella Grassmayr, Paul Kapitza, Teresa Kaserer, Ronald Gust
Summary: This study identifies a promising therapeutic strategy for breast cancer by targeting both the ligand binding site and the coactivator binding site of estrogen receptor alpha. The synthesized compounds show strong inhibition of tumor growth and estrogen-induced activation, making them potential anti-cancer agents.
ARCHIV DER PHARMAZIE
(2023)
Article
Biochemistry & Molecular Biology
Kiminori Ohta, Asako Kaise, Takumi Ogawa, Yasuyuki Endo
Summary: In this study, a novel estrogen receptor modulator Az-01 was developed as an alternative to tamoxifen for breast cancer treatment. Az-01 exhibited similar estrogen receptor binding affinity to tamoxifen, but acted as a partial agonist and showed potent anti-estrogenic activity in the presence of estrogen. Furthermore, Az-01 demonstrated specific cell proliferation and inhibition activities in ER-expressing cells without affecting other cell proliferation signals.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Chih-Jung Chen, Ting-Hao Chen, Jason Lei, Ji-An Liang, Po-Sheng Yang, Chiun-Sheng Huang, Chia-Ming Hsieh, Ling-Ming Tseng, Liang-Chih Liu, Skye Hung-Chen Cheng, Kuan-Hui Shih
Summary: This study compared the biomarker expression and breast cancer subtyping results obtained by immunohistochemistry (IHC) and reverse transcriptase-polymerase chain reaction (RT-PCR). The results showed concordance between the two methods, and RT-PCR performed similarly to IHC in predicting 5-year survival.
BIOSCIENCE REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Alok Mishra, Anshuman Srivastava, Ankit Pateriya, Manendra Singh Tomar, Anand Kumar Mishra, Ashutosh Shrivastava
Summary: Breast cancer is the most common cancer among females, and endocrine therapy for ER-positive breast cancer can result in acquired resistance. The metabolic state of cancer cells plays a crucial role in their susceptibility to chemotherapeutic drugs, and understanding metabolic pathway alterations in TAMR cancer may offer potential therapeutic strategies.
CHEMICO-BIOLOGICAL INTERACTIONS
(2021)
Article
Chemistry, Medicinal
Alexandra K. Knox, Christina Kalchschmid, Daniela Schuster, Francesca Gaggia, Ronald Gust
Summary: The compound GW7604, a derivative of (Z)-4-hydroxy-tamoxifen, was linked to molecules that bind to the coactivator binding site, resulting in an optimized pharmacological profile. Thioxo-quinazolinone derivative 16 showed high affinity to estrogen receptor beta and acted as a pure estradiol antagonist, demonstrating selective ER degradation/downregulation.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Oncology
Nivida Shete, Jordan Calabrese, Debra A. Tonetti
Summary: Estrogen is a key driver of estrogen-receptor-positive breast cancers, and drugs that block estrogen signaling are commonly used for treatment. Surprisingly, estrogen was previously used to treat breast cancer before the introduction of tamoxifen. This review focuses on the insights, molecular mechanisms, and potential clinical application of this counterintuitive therapeutic approach.
Article
Pharmacology & Pharmacy
Faten Shehadeh-Tout, Heloisa H. Milioli, Suraya Roslan, Patric J. Jansson, Mahendiran Dharmasivam, Dinny Graham, Robin Anderson, Tharushi Wijesinghe, Mahan Gholam Azad, Des R. Richardson, Zaklina Kovacevic
Summary: This study investigates a new class of anti-cancer agents for the treatment of ER-positive breast cancer. These agents inhibit multiple growth factor receptors and down-stream signaling, leading to decreased expression of hormone receptors and key resistance pathways. In vivo experiments demonstrate that these agents effectively inhibit ER-positive breast cancer growth. This represents an innovative non-hormonal, multi-modal therapeutic approach.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Oncology
Craig Furman, Xiaoling Puyang, Zhaojie Zhang, Zhenhua J. Wu, Deepti Banka, Kiran B. Aithal, Lee A. Albacker, Ming-Hong Hao, Sean Irwin, Amy Kim, Meagan Montesion, Alyssa D. Moriarty, Karthikeyan Murugesan, Tuong-Vi Nguyen, Victoria Rimkunas, Tarek Sahmoud, Michael J. Wick, Shihua Yao, Xun Zhang, Hao Zeng, Frederic H. Vaillancourt, David M. Bolduc, Nicholas Larsen, Guo Zhu Zheng, Sudeep Prajapati, Ping Zhu, Manav Korpal
Summary: H3B-6545 is an ER alpha covalent antagonist that demonstrates promising preclinical activity against CDK4/6i naive and resistant ER alpha(WT) and ER alpha(MUT) tumors.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Oncology
Jonathan Welti, Adam Sharp, Nigel Brooks, Wei Yuan, Christopher McNair, Saswati N. Chand, Abhijit Pal, Ines Figueiredo, Ruth Riisnaes, Bora Gurel, Jan Rekowski, Denisa Bogdan, William West, Barbara Young, Meera Raja, Amy Prosser, Jordan Lane, Stuart Thomson, Jenny Worthington, Stuart Onions, Jonathan Shannon, Silvia Paoletta, Richard Brown, Don Smyth, Gareth W. Harbottle, Veronica S. Gil, Susana Miranda, Mateus Crespo, Ana Ferreira, Rita Pereira, Nina Tunariu, Suzanne Carreira, Antje J. Neeb, Jian Ning, Amanda Swain, David Taddei, Matthew J. Schiewer, Karen E. Knudsen, Neil Pegg, Johann S. de Bono
Summary: The resistance to AR blockade in CRPC is associated with sustained AR signaling through alternative splicing of AR (AR-SV). Inhibitors of transcriptional coactivators like p300/CBP are attractive therapeutic targets for lethal prostate cancer. CCS1477, a novel small-molecule inhibitor of p300/CBP, shows promise in inhibiting cell proliferation in prostate cancer cell lines and regulating AR and C-MYC signaling.
Article
Clinical Neurology
Carmen M. Avram, Barbara H. Brumbach, Amie L. Hiller
Summary: The findings suggest that exposure to tamoxifen in women with breast cancer may increase the risk of Parkinson's disease, but overall rates of PD in this population appear to be low. Further research is needed to clarify the role of estrogen and selective estrogen antagonism in PD.
MOVEMENT DISORDERS
(2021)
Article
Cell Biology
Ingrid Espinoza, Lin Yang, Travis Vander Steen, Luciano Vellon, Elisabet Cuyas, Sara Verdura, Lester Lau, Javier A. Menendez, Ruth Lupu
Summary: CCN1 promotes angiogenesis, tumor growth, and chemoresistance in endothelial and breast cancer cells by binding to its integrin receptor α(v)β(3). It also controls tissue regeneration by engaging its integrin receptor α(6)β(1) to induce fibroblast senescence. In estrogen receptor-positive breast cancer cells, CCN1 drives an endocrine resistance phenotype through its interaction with ER α.
Article
Medicine, Research & Experimental
Coralie Poulard, Thuy Ha Pham, Youenn Drouet, Julien Jacquemetton, Ausra Surmielova, Loay Kassem, Benoite Mery, Christine Lasset, Jonathan Reboulet, Isabelle Treilleux, Elisabetta Marangoni, Olivier Tredan, Muriel Le Romancer
Summary: Endocrine therapies targeting estrogen signaling have improved management of estrogen receptor alpha (ERα)-positive breast cancers. However, resistance to treatment remains a challenge. This study identifies nuclear PRMT5 expression as a predictive marker of sensitivity to tamoxifen in breast cancer patients, and reveals the mechanism of tamoxifen stimulating ERα methylation by PRMT5. This biomarker could be used to enhance response to tamoxifen in ERα-positive breast tumors.
EMBO MOLECULAR MEDICINE
(2023)
Article
Chemistry, Medicinal
Leah L. Lowder, Matthew Powell, Sean E. Miller, Rigel J. Kishton, Charles B. Kelly, Connor B. Cribb, Kelly Mastro-Kishton, Manoj Chelvanambi, Phat T. Do, Rajeshwar Reddy Govindapur, Suzanne E. Wardell, Donald P. McDonnell, Libero J. Bartolotti, Giridhar R. Akkaraju, Arthur R. Frampton, Sridhar Varadarajan
Summary: DNA-alkylating compounds selectively target breast cancer cells by facilitating ERα translocation to the nucleus and inducing ERα target gene expression; minor structural changes significantly impact DNA binding and methylating abilities of the compounds; this approach may overcome limitations of current chemotherapy agents.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Shaimaa Hamza, Ekaterina E. E. Garanina, Mohammad Alsaadi, Svetlana F. F. Khaiboullina, Gulcin Tezcan
Summary: NLRP3 may contribute to the growth and propagation of breast cancer, and the effects of ER-alpha, PR, and HER2 on NLRP3 activation in breast cancer are still unknown.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Ray Kreienkamp, Cyrielle Billon, Gonzalo Bedia-Diaz, Carolyn J. Albert, Zacharie Toth, Andrew A. Butler, Sara McBride-Gagyi, David A. Ford, Angel Baldan, Thomas P. Burris, Susana Gonzalo
Article
Multidisciplinary Sciences
Christina Chang, Chin-San Loo, Xuan Zhao, Laura A. Solt, Yuqiong Liang, Sagar P. Bapat, Han Cho, Theodore M. Kamenecka, Mathias Leblanc, Annette R. Atkins, Ruth T. Yu, Michael Downes, Thomas P. Burris, Ronald M. Evans, Ye Zheng
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Editorial Material
Cell Biology
Thomas P. Burris
NATURE CELL BIOLOGY
(2020)
Article
Multidisciplinary Sciences
Jinsai Shang, Sarah A. Mosure, Jie Zheng, Richard Brust, Jared Bass, Ashley Nichols, Laura A. Solt, Patrick R. Griffin, Douglas J. Kojetin
NATURE COMMUNICATIONS
(2020)
Article
Multidisciplinary Sciences
Ryan D. Welch, Cyrielle Billon, Amina Kameric, Thomas P. Burris, Colin A. Flaveny
Article
Pharmacology & Pharmacy
Zdenek Dvorak, Max Klapholz, Thomas P. Burris, Benjamin P. Willing, Antimo Gioiello, Roberto Pellicciari, Francesco Galli, John March, Stephen J. O'Keefe, R. Balfour Sartor, Chang H. Kim, Maayan Levy, Sridhar Mani
MOLECULAR PHARMACOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Mohamed Shahien, Mohamed Elagawany, Sadichha Sitaula, Shaimaa S. Goher, Sheryl L. Burris, Ryan Sanders, Amer Avdagic, Cyrielle Billon, Lamees Hegazy, Thomas P. Burris, Bahaa Elgendy
BIOORGANIC CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Paola Munoz-Tello, Hua Lin, Pasha Khan, Ian Mitchelle S. de Vera, Theodore M. Kamenecka, Douglas J. Kojetin
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Nelson E. Bruno, Jerome C. Nwachukwu, Sathish Srinivasan, Charles C. Nettles, Tina Izard, Zhuang Jin, Jason Nowak, Michael D. Cameron, Siddaraju V. Boregowda, Donald G. Phinney, Olivier Elemento, Xu Liu, Eric A. Ortlund, Rene Houtman, Diana A. Stavreva, Gordon L. Hager, Theodore M. Kamenecka, Douglas J. Kojetin, Kendall W. Nettles
Summary: The study found that ligand class analysis can predict the effects of glucocorticoid receptor ligands on myocyte metabolism and protein balance, identifying compounds with muscle-sparing and protein synthesis effects. This method provides a new approach to understand the link between the ligand-receptor interface and physiological outcomes.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jinsai Shang, Douglas J. Kojetin
Summary: By using nuclear magnetic resonance spectroscopy, isothermal titration calorimetry, and surface plasmon resonance analysis, it was shown that structurally distinct agonists bind to PPAR gamma through a two-step induced fit mechanism, involving an initial fast kinetic step followed by a slow conformational change. The findings suggest an activation mechanism for PPAR gamma where agonist binding proceeds through an initial encounter complex followed by a transition of the ligand into the final binding pose within the orthosteric pocket, inducing a transcriptionally active conformation.
Correction
Chemistry, Medicinal
Paola Munoz-Tello, Hua Lin, Pasha Khan, Ian Mitchelle S. de Vera, Theodore M. Kamenecka, Douglas J. Kojetin
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Mei Lan Chen, Xiangsheng Huang, Hongtao Wang, Courtney Hegner, Yujin Liu, Jinsai Shang, Amber Eliason, Huitian Diao, HaJeung Park, Blake Frey, Guohui Wang, Sarah A. Mosure, Laura A. Solt, Douglas J. Kojetin, Alex Rodriguez-Palacios, Deborah A. Schady, Casey T. Weaver, Matthew E. Pipkin, David D. Moore, Mark S. Sundrud
Summary: The study identified the nuclear xenobiotic receptor CAR as a regulator of MDR1 expression in T cells, protecting the small intestine from bile acid toxicity and inflammation. Activation of CAR in T-eff cells infiltrating the small intestine induced large-scale transcriptional reprogramming and promoted the expression of the anti-inflammatory cytokine IL-10.
Article
Multidisciplinary Sciences
Dilani G. Gamage, Kamran Melikov, Paola Munoz-Tello, Tanner J. Wherley, Leah C. Focke, Evgenia Leikina, Elliana Huffman, Jiajie Diao, Douglas J. Kojetin, Vikram Prasad, Leonid Chernomordik, Douglas P. Millay
Summary: Muscle cell fusion is a complex process involving the activity of Myomerger protein. The two alpha-helices of Myomerger possess unique characteristics and work together to achieve full protein activity. Externalized phosphatidylserine (PS) plays a crucial role in regulating Myomerger activity by inducing a conformational change in the alpha-helices and enhancing membrane interactions. These findings reveal the spatial and temporal regulation of Myomerger activity during the final steps of myoblast fusion.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Sarah A. Mosure, Timothy S. Strutzenberg, Jinsai Shang, Paola Munoz-Tello, Laura A. Solt, Patrick R. Griffin, Douglas J. Kojetin
Summary: Heme is an endogenous ligand for REV-ERB nuclear receptors, regulating their activity by binding with corepressor NCoR and influencing the thermodynamic interaction profile between NCoR and REV-ERBβ. This finding sheds light on the mechanism of heme-dependent REV-ERB activity.
Article
Biochemistry & Molecular Biology
Kristine Griffett, Gonzalo Bedia-Diaz, Lamees Hegazy, Ian Mitchelle S. de Vera, Udayanga S. Wanninayake, Cyrielle Billon, Thomas Koelblen, McKenna L. Wilhelm, Thomas P. Burris
CELL CHEMICAL BIOLOGY
(2020)