Article
Chemistry, Multidisciplinary
Zhimei Lin, Bingyang Chu, Ying Qu, Xue Wei, Jingcao Huang, Fangfang Wang, Yu Feng, Xin Wang, Hongmei Luo, Xinyu Zhai, Juan Xu, Xiang Liu, Li Zhang, Fengjiao Chen, Yu Wu, Yuhuan Zheng
Summary: In this study, the researchers loaded melphalan into a liposomal capsule to create liposomal melphalan (liposomal MEL). The liposomal MEL showed stable properties and efficient uptake by multiple myeloma cells in vitro. In animal models, liposomal MEL exhibited reduced organ toxicity and demonstrated strong anti-myeloma activity in vivo.
Article
Oncology
Xuejie Gao, Bo Li, Anqi Ye, Houcai Wang, Yongsheng Xie, Dandan Yu, Zhijian Xu, Bingqing Shi, Hui Zhang, Qilin Feng, Ke Hu, Yong Zhang, Cheng Huang, Guang Yang, Jumei Shi, Weiliang Zhu
Summary: DCZ0805 effectively inhibited multiple myeloma cell survival by inducing apoptosis, suppressing the activation of the NF-kappa B signaling pathway, and inhibiting cell proliferation. Additionally, it significantly reduced tumor burden in a xenograft mouse model without noticeable toxicity.
CANCER CELL INTERNATIONAL
(2021)
Article
Chemistry, Medicinal
Zhanhui Li, Yongjin Hao, Chengkui Yang, Qing Yang, Shuwei Wu, Haikuo Ma, Sheng Tian, Haohao Lu, Jingrui Wang, Tao Yang, Sudan He, Xiaohu Zhang
Summary: This study reports a series of potent RIPK1 inhibitors, with compound 70 being highly active and stable in blocking necroptosis in inflammatory signaling and cell death. Compound 70 exhibits excellent properties and activity in both in vitro and in vivo experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Lin-Hao Zhang, Ming-Yue Li, Da-Yuan Wang, Xue-Jun Jin, Fen-Er Chen, Hu-Ri Piao
Summary: The study synthesized 23 mollugin derivatives, among which compound 6d exhibited the most promising inhibitory activity against NF-kappa B without significant cytotoxicity. Most compounds showed potent anti-inflammatory activity, with compound 4f being the most effective after intraperitoneal administration, exhibiting good pharmacokinetics and drug-like behavior.
Article
Plant Sciences
Jiyoon Park, Jiseong Kim, Sunghoon Hwang, Daehyun Oh, Young Eun Du, Sang-Jip Nam, Hyeung-geun Park, Min Jae Lee, Dong-Chan Oh
Summary: New sulfur-bearing natural products, sadopeptins A and B, were discovered from Streptomyces sp. YNK18 through a targeted search using the isotopic signature of sulfur. The compounds were determined to be new cyclic heptapeptides with specific functional groups through NMR spectroscopy and other analyses. The findings also revealed the presence of a biosynthetic gene cluster and proposed a potential biosynthetic pathway. The sadopeptins showed proteasome-inhibitory activity without affecting cellular autophagic flux.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Microbiology
Sherman Chu, Lisa Long, Thomas S. McCormick, Katyna Borroto-Esoda, Stephen Barat, Mahmoud A. Ghannoum
Summary: Echinocandins are a first-line therapy for Candida infections due to their ability to inhibit the synthesis of polymer beta-(1,3)-d-glucan. SCY-247, a second-generation glucan synthase inhibitor, has shown promising results in combating invasive fungal infections caused by Candida albicans, with decreased fungal burden and improved survival rates observed in murine models. This study suggests that SCY-247 is a potential novel anti-fungal agent with significant activity against Candida infections, indicating potential for further development and clinical application.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Kazuki Ishikawa, Masaki Ishii, Takashi Yaguchi, Toshiaki Katada, Koji Ichinose, Shinya Ohata
Summary: The nuclear factor-kappa B (NF-kappa B) signaling pathway plays a crucial role in inflammatory responses and cancer pathogenesis. In this study, the alkaloid aszonalenin and its analog epi-aszonalenin B were identified as inhibitors of NF-kappa B activity, making them potential therapeutic compounds for supratentorial ependymomas (ST-EPN-RELA).
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Chemistry, Analytical
Yi Qu, Zhongsheng Xu, Jiemen Wang, Wei Liu, Anam Iqbal, Kanwal Iqbal, Yaling Su, Yuping Cao, Jilu Yang, Wenwu Qin, Yun Liu
Summary: A novel fluorescent probe NBD-3 was developed to detect endogenous chymotrypsin. Through computation and spectral testing, the best probe NBD-3 with rare bright red fluorescence was screened. The presence of endogenous chymotrypsin was discovered for the first time in the liver of mice through confocal imaging, in vivo imaging, and in vitro imaging of organs. NBD-3's strong performance allows real-time detection of chymotrypsin medications.
SENSORS AND ACTUATORS B-CHEMICAL
(2023)
Article
Chemistry, Medicinal
Weilin Chen, Xin Chen, Dongdong Li, Xianghan Wang, Guanlu Long, Zhengyu Jiang, Qidong You, Xiaoke Guo
Summary: The MLL1-WDR5 interaction is crucial for the formation of the MLL core complex and its H3K4 methyltransferase activity. Disrupting this interaction has been suggested as a potential therapeutic approach for leukemia. By developing a novel MLL1-WDR5 interaction blocker, the research team successfully identified the best inhibitor 24 with high binding affinity and improved drug-like properties.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Kathryn M. Pflug, Dong W. Lee, Ashutosh Tripathi, Vytas A. Bankaitis, Kevin Burgess, Raquel Sitcheran
Summary: The study suggests that Crizotinib holds potential as a treatment for GBM, although its effectiveness is limited due to poor penetration of the blood brain barrier. Additionally, conjugation of Crizotinib with a dye showed improved inhibition of glioma cell proliferation and survival. Furthermore, IR-Crizotinib demonstrated effective tumor localization and growth inhibition in mice.
MOLECULAR PHARMACEUTICS
(2023)
Article
Chemistry, Medicinal
Xufen Yu, Jia Xu, Yudao Shen, Kaitlyn M. Cahuzac, Kwang-Su Park, Brandon Dale, Jing Liu, Ramon E. Parsons, Jian Jin
Summary: In this study, we reported a potent AKT degrader MS21 and its structure-activity relationship (SAR) studies. Additionally, we discovered another VHL-recruiting AKT degrader MS143 with similar efficacy as MS21, as well as a novel CRBN-recruiting PROTAC MS5033. These compounds effectively degraded AKT by hijacking the ubiquitin-proteasome system and showed significant inhibition of cell growth in multiple cancer cell lines. Furthermore, they exhibited good plasma exposure levels in mice and were suitable for in vivo studies.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Danli Zhou, Yingying Zuo, Zhengying Pan
Summary: This study reports the development of cereblon-recruiting ITK proteolysis targeting chimeras based on a structure-based design strategy, which holds great therapeutic potential for human autoimmune diseases and T-cell malignant lymphomas. Two representative compounds, 23 and 28, demonstrated potent ITK degradation and IL-2 inhibition activities in Jurkat cells. Global proteomic profiling assays confirmed the high selectivity of compounds 23 and 28 as ITK degraders. Compound 28 exhibited efficient, rapid, and prolonged ITK degradation in mice, along with significant suppression of IL-2 secretion. It is the first effective and highly selective ITK degrader, serving as a valuable tool compound for further investigation of ITK degradation in human diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Yongjin Hao, Chengkui Yang, Chang Shu, Zhanhui Li, Kaijiang Xia, Shuwei Wu, Haikuo Ma, Sheng Tian, Yuting Ji, Jingjing Li, Sudan He, Xiaohu Zhang
Summary: This study identified compound 36 as an inhibitor of necroptosis and optimized its scaffold to obtain a series of potent compounds. Among them, compound 56 showed excellent pharmacological properties, effectively binding and inhibiting RIPK1, and had the potential for treating inflammation-related diseases.
BIOORGANIC CHEMISTRY
(2022)
Review
Oncology
Xin Li, Yinling Hu
Summary: CHUK/IKK alpha has emerged as a novel tumor suppressor in several human and mouse organs, with a strong association with NF-kappa B. However, the roles of IKK alpha and NF-kappa B in normal organ development, disease, and cancer pathogenesis require further investigation.
Article
Oncology
Jie Liu, Shengjun Sun, Cheng Zhou, Zhihong Sun, Qin Wang, Chengming Sun
Summary: NF-kappa B transcription factors play a critical role in important cellular processes. This study identified Lycorine as an inhibitor of the NF-kappa B signaling pathway, with potential anticancer activity against prostate cancer.
Article
Oncology
Eyal Lebel, Christine Chen, Harminder Paul, Suzanne Trudel, Rodger Tiedemann
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2021)
Article
Biophysics
Georgina Daher-Reyes, TaeHyung Kim, Igor Novitzky-Basso, Kyuoung Ha Kim, Adam Smith, Tracy Stockley, Jose-Mario Capochichi, Zeyad Al-Shaibani, Ivan Pasic, Arjun Law, Wilson Lam, Fotios V. Michelis, Armin Gerbitz, Auro Viswabandya, Jeffrey Lipton, Rajat Kumar, Jonas Mattsson, Aaron Schimmer, Caroline McNamara, Tracy Murphy, Dawn Maze, Vikas Gupta, Hassan Sibai, Steven Chan, Karen Yee, Mark Minden, Zhaolei Zhang, Andre Schuh, Dennis D. H. Kim
Summary: The study found that adverse molecular-genetic profiles significantly affect the outcomes of acute myeloid leukemia patients following allogeneic hematopoietic stem cell transplantation, with TP53 mutation, MK, CK, and monosomy 7 being associated with poorer survival and higher relapse rates.
BONE MARROW TRANSPLANTATION
(2021)
Review
Oncology
Yue Feng, Kazem Nouri, Aaron D. Schimmer
Summary: Changes in cellular metabolism, bioenergetics, oxidative stress, and ROS levels are characteristics of cancer development. ATP-dependent proteases, especially ClpXP, play a crucial role in regulating mitochondrial function and are being investigated as a potential therapeutic target for certain malignancies. Targeting ClpXP can disrupt mitochondrial protein homeostasis and affect cancer cell viability.
Article
Biochemistry & Molecular Biology
Alfonso Rivera Duarte, Donna Reece, Xuan Li, Wei Xu, Harminder Paul, Esther Masih-Khan, Andrew Winter, Rodger Tiedemann, Anca Prica, Christine Chen, Suzanne Trudel, Vishal Kukreti
Summary: Extended duration treatment in patients with systemic light chain amyloidosis is associated with better progression free survival (PFS) and deeper organ responses. However, the impact on overall survival (OS) is not significant, and further prospective studies are needed to analyze this correlation.
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2022)
Article
Biochemical Research Methods
Ali Mahdipour-Shirayeh, Natalie Erdmann, Chungyee Leung-Hagesteijn, Rodger E. Tiedemann
Summary: This study presents a high-throughput analysis pipeline that provides paired CNV profiles and transcriptomes for single cells, enabling the investigation of the effects of CNVs on cellular programs. The authors describe new normalization methods and a tool for inferring CNVs from scRNA-seq data, which show improved sensitivity and specificity compared to existing methods. Using these tools, they demonstrate the cellular effects of CNVs in multiple myeloma.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Oncology
Safa Majeed, Mansi K. Aparnathi, Kevin C. J. Nixon, Vidhyasagar Venkatasubramanian, Fariha Rahman, Lifang Song, Jessica Weiss, Ranya Barayan, Vijithan Sugumar, Samir H. Barghout, Joel D. Pearson, Rod Bremner, Aaron D. Schimmer, Ming S. Tsao, Geoffrey Liu, Benjamin H. Lok
Summary: TAK-243 exhibits efficacy in preclinical models of small cell lung cancer (SCLC), with associations to various gene sets. TAK-243 synergizes with cisplatin/etoposide chemotherapy (C/E) and PARP inhibitor olaparib. TAK-243 is a potential therapeutic strategy to improve SCLC patient outcomes.
CLINICAL CANCER RESEARCH
(2022)
Article
Hematology
Eyal Lebel, Xuan Li, Harminder Paul, Esther Masih-Khan, Sita Bhella, Christine Chen, Anca Prica, Donna Reece, Rodger Tiedemann, Suzanne Trudel, Vishal Kukreti
Summary: The study found that the time to best response to second-line therapy is predictive of a favorable outcome, while it is not a predictor for first-line therapy. Patients with IgA-MM clear their M-spike faster than IgG-MM, but the clearance of LC is similar in both subtypes. Prospective analysis may provide more insights into unresolved questions.
EUROPEAN JOURNAL OF HAEMATOLOGY
(2022)
Correction
Chemistry, Medicinal
David E. Uehling, Babu Joseph, Kim Chan Chung, Andrew X. Zhang, Spencer Ler, Michael A. Prakesch, Gennady Poda, Julie Grouleff, Ahmed Aman, Taira Kiyota, Chungyee Leung-Hagesteijn, John David Konda, Richard Marcellus, Carly Griffin, Ratheesh Subramaniam, Ayome Abibi, Craig A. Strathdee, Methvin B. Isaac, Rima Al-Awar, Rodger E. Tiedemann
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Letter
Hematology
Baolin Tang, Jong Bok Lee, Siqi Cheng, Tianzhong Pan, Wen Yao, Dongyao Wang, Meijuan Tu, Zhiqiang Xiang, Xiandeng Chu, Liangquan Geng, Ping Qiang, Pingping Teng, Guangyu Sun, Huilan Liu, Jian Wang, Aaron D. Schimmer, Liming Yang, Zimin Sun, Li Zhang, Xiaoyu Zhu
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Article
Medicine, General & Internal
Lindsay A. Jibb, Stephanie M. Nanos, Sarah Alexander, Carmine Malfitano, Anne Rydall, Sumit Gupta, Aaron D. Schimmer, Camilla Zimmermann, Sarah Hales, Rinat Nissim, Charles Marmar, Katharina Schultebraucks, Kenneth Mah, Gary Rodin
Summary: This study aims to determine the prevalence, severity, longitudinal course, and predictors of traumatic stress symptoms in family caregivers of patients with acute leukemia and to understand their lived experience of traumatic stress and support needs.
Article
Medicine, Research & Experimental
Danielle C. Croucher, Anup Joseph Devasia, Dor D. Abelman, Ali Mahdipour-Shirayeh, Zhihua Li, Natalie Erdmann, Rodger Tiedemann, Trevor J. Pugh, Suzanne Trudel
Summary: Genomic characterization of cancer has led to advances in personalized medicine, but precision medicine in multiple myeloma has been limited due to subclonal molecular targets. Targeting FGFR3 in MM has been under development, and a clinical trial evaluating the small-molecule FGFR1-4 inhibitor erdafitinib was conducted. The study found that single-cell genomics revealed the intended molecular response and highlighted the utility of this approach in guiding personalized and targeted therapies.
COLD SPRING HARBOR MOLECULAR CASE STUDIES
(2023)
Article
Oncology
Eyal Lebel, Katherine Lajkosz, Esther Masih-Khan, Donna Reece, Suzanne Trudel, Rodger Tiedemann, Anca Prica, Vishal Kukreti, Christine Chen
Summary: Higher yields of stem-cells collected for autologous transplantation may indicate improved outcomes in multiple myeloma (MM). However, some of the most efficient mobilizers have worse progression-free survival, possibly due to treatment variables related to both collection yields and myeloma outcomes.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Article
Immunology
Ioannis D. Dimitriou, David Meiri, Yulia Jitkova, Alisha R. Elford, Marianne Koritzinsky, Aaron D. Schimmer, Pamela S. Ohashi, Nahum Sonenberg, Robert Rottapel
Summary: In this study, the researchers found that 4E-BP1/2 proteins play a critical role in the proliferation of mouse CD8(+) T cells and the development of antiviral effector function. They also discovered that the translation of genes related to mitochondrial biogenesis is impaired in T cells derived from 4E-BP1/2-deficient mice.
JOURNAL OF IMMUNOLOGY
(2022)
Correction
Biochemistry & Molecular Biology
Qi Zhang, Bridget Riley-Gillis, Lina Han, Yannan Jia, Alessia Lodi, Haijiao Zhang, Saravanan Ganesan, Rongqing Pan, Sergej N. Konoplev, Shannon R. Sweeney, Jeremy A. Ryan, Yulia Jitkova, Kenneth Dunner, Shaun E. Grosskurth, Priyanka Vijay, Sujana Ghosh, Charles Lu, Wencai Ma, Stephen Kurtz, Vivian R. Ruvolo, Helen Ma, Connie C. Weng, Cassandra L. Ramage, Natalia Baran, Ce Shi, Tianyu Cai, Richard Eric Davis, Venkata L. Battula, Yingchang Mi, Jing Wang, Courtney D. DiNardo, Michael Andreeff, Jeffery W. Tyner, Aaron Schimmer, Anthony Letai, Rose Ann Padua, Carlos E. Bueso-Ramos, Stefano Tiziani, Joel Leverson, Relja Popovic, Marina Konopleva
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)
Article
Endocrinology & Metabolism
Mathepan Jeya Mahendralingam, Hyeyeon Kim, Curtis William McCloskey, Kazeera Aliar, Alison Elisabeth Casey, Pirashaanthy Tharmapalan, Davide Pellacani, Vladimir Ignatchenko, Mar Garcia-Valero, Luis Palomero, Ankit Sinha, Jennifer Cruickshank, Ronak Shetty, Ravi N. Vellanki, Marianne Koritzinsky, Vid Stambolic, Mina Alam, Aaron David Schimmer, Hal Kenneth Berman, Connie J. Eaves, Miquel Angel Pujana, Thomas Kislinger, Rama Khokha
Summary: Cancer cells adapt their metabolic network from the tissue of origin. Normal mammary cells exhibit diverse metabolic programs, with basal cells enriched in glycolysis and luminal progenitors in oxidative phosphorylation. Targeting these metabolic vulnerabilities in mammary progenitors could potentially advance breast cancer therapy, as breast cancer subtypes retain metabolic features of their putative cell of origin.