Article
Chemistry, Medicinal
Inhwan Bae, Daejin Kim, Jaeyul Choi, Jisook Kim, Minjeong Kim, Bokyung Park, Young Hoon Kim, Young Gil Ahn, Ha Hyung Kim, Dae Kyong Kim
Summary: The newly designed and synthesized bivalent analogue 27 showed significant increase in cellular activity and caused substantial tumor regressions in MDA-MB-231 xenograft model, indicating its promising potential as an effective anti-tumor agent.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Hematology
Naveen Pemmaraju, Bing Z. Carter, Prithviraj Bose, Nitin Jain, Tapan M. Kadia, Guillermo Garcia-Manero, Carlos E. Bueso-Ramos, Courtney D. DiNardo, Sharon Bledsoe, Naval G. Daver, Uday Popat, Marina Y. Konopleva, Lingsha Zhou, Sherry Pierce, Zeev E. Estrov, Gautam M. Borthakur, Maro Ohanian, Wei Qiao, Lucia Masarova, Xuemei Wang, Po Yee Mak, Jorge Cortes, Elias Jabbour, Srdan Verstovsek
Summary: Treatment with SMAC mimetic LCL161 in high-risk and treatment-resistant MF patients showed a 30% objective response rate, with 6 patients achieving clinical improvement in anemia. The median overall survival was 34 months, and while there were some adverse events, two deaths during the study period were unrelated to the study drug.
Article
Cell Biology
Lidia F. Hernandez, Angie B. Dull, Soumya Korrapati, Christina M. Annunziata
Summary: Ovarian cancer, the most lethal gynecological cancer in the US, is characterized by resistance to chemotherapy. Low Caspase 8 expression levels are associated with resistance to apoptotic chemotherapy in ovarian cancers. Combination treatment with a Smac-mimetic can increase cell death in tumor cells with low Caspase 8, leading to decreased tumor growth and enhanced overall survival in mouse models. Timing of drug administration is crucial for optimizing treatment outcomes.
CELL DEATH DISCOVERY
(2021)
Article
Biochemistry & Molecular Biology
David Reigada, Rodrigo M. Maza, Teresa Munoz-Galdeano, Maria Asuncion Barreda-Manso, Altea Soto, Dan Lindholm, Rosa Navarro-Ruiz, Manuel Nieto-Diaz
Summary: Mechanical trauma to the spinal cord leads to neuronal death and loss of sensory-motor and autonomic functions. Overexpression of XIAP in neurons can improve survival and functional recovery after SCI by inhibiting caspase activity and apoptosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Surgery
Ruping Xiang, Juan Xu, Huiyun Yu, Yujuan Huang, Zhi Li, Cheng Yu, Li Wang, Min Fu, Qiong Chen
Summary: This study investigates the effects of butylphthalide on the expression of Smac and XIAP in the ischemic semidark area of rats. The results demonstrate that butylphthalide significantly reduces neuronal apoptosis induced by ischemia-reperfusion injury and has neuroprotective effects.
JOURNAL OF SURGICAL RESEARCH
(2023)
Article
Biology
David Cerna, Bora Lim, Yusuf Adelabu, Stephen Yoo, Donna Carter, Ahmed Fahim, Yasuhiro Mitsuuchi, Beverly A. Teicher, Eric Bernhard, C. Norman Coleman, Naoko Takebe, Mansoor M. Ahmed
Summary: Research has shown that birinapant can enhance the radiosensitivity of glioblastoma cell lines, with particularly significant effects observed in the U-251 cell line. The combination treatment of birinapant and radiation therapy demonstrated tumor growth delay and a survival benefit in both in vitro and in vivo models, warranting further investigation into this potential treatment approach.
RADIATION RESEARCH
(2021)
Article
Chemistry, Medicinal
Seungbeom Lee, Jisu Kim, Jeyun Jo, Jae Won Chang, Jaehoon Sim, Hwayoung Yun
Summary: Bivalent kinase inhibitors have emerged as a promising approach for targeting specific kinases with enhanced selectivity and affinity through increased interactions with target enzymes. Recent developments have led to the creation of bivalent compounds with high kinase affinity, biological and chemical stability in vivo, offering significant potential for therapeutic applications. This review provides a comprehensive overview of hetero-bivalent kinase inhibitors and discusses their advantages, limitations, and future prospects compared to monovalent kinase inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Shaikh Maryam Ghufran, Sachin Sharma, Sampa Ghose, Subhrajit Biswas
Summary: TNF alpha induces cell survival in activated hepatic stellate cells (HSCs) through NF-kappa B signaling, and cIAP2 plays a regulatory role in this process. Inhibition of cIAP2 can attenuate TNF alpha-induced cell viability and activation of the NF-kappa B signaling pathway, and it has anti-proliferative effects on activated HSCs. Targeting cIAP2 in the NF-kappa B signaling pathway may be a promising approach for the treatment of liver fibrosis.
MOLECULAR BIOLOGY REPORTS
(2023)
Article
Medicine, General & Internal
Ning Jiang, Wei-Quan Zhang, Hong Dong, Ying-Tao Hao, Li-Ming Zhang, Lei Shan, Xiao-Dong Yang, Chuan-Liang Peng
Summary: LCL161, an SMAC analog, inhibits proliferation and induces apoptosis in esophageal cancer cells by regulating the expression of IAP family members, suggesting its potential as an effective treatment for esophageal squamous cell carcinoma.
WORLD JOURNAL OF CLINICAL CASES
(2021)
Article
Biology
Sahar Rafat, Prabhakar Singh, Kamlesh Kumar Pandey, Saleh A. Almatroodi, Mohammed A. Alsahli, Ahmad Almatroudi, Arshad Husain Rahmani, Kapil Dev
Summary: This study investigates the role of SMAC mimetic compound BV6 in regulating cell death mechanisms and its potential anti-cancer effect in combination with TRAIL and TNFα in breast cancer cells. The study suggests that BV6 alone and in combination with TRAIL and TNFα show promising results in inhibiting cancer growth. Additionally, IAPs and autophagic proteins may serve as important targets for the development of novel anti-cancer drugs.
Article
Biochemistry & Molecular Biology
Takuya Otani, Yasunao Hattori, Kenichi Akaji, Kazuya Kobayashi
Summary: In this study, a cross-linked structure between the P1 and P3 side chains was introduced in the inhibitor of BACE1 to enhance inhibitory activity. Through the synthesis and evaluation of fragments with different side chain lengths, a 13-membered ring with a dimethyl branched substituent at the P3 beta-position was found to be optimal and significantly more active. The introduction of a 4-carboxymethylphenyl group at the P1' position further improved the activity of the inhibitor.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Hua Chen, Xi Liu, Yun Wu, Xiayin Wu, Xiaoli Wen, Yanan Lu, Xingsheng Zhao
Summary: Atherosclerosis is a serious disease, and miR-616-3p promotes endothelial cell apoptosis by inhibiting the expression of XIAP mRNA, thus playing a role in the development of atherosclerosis.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Article
Oncology
Chuanhui Lu, Ming Hong, Bo Chen, Kaihua Liu, You Lv, Xin Zhou, Guoqiang Su
Summary: The study demonstrated that miR-215 promotes apoptosis in colon cancer cells by inhibiting XIAP expression. There is an interaction mechanism between miR-215 and XIAP.
CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
(2021)
Review
Engineering, Chemical
Yung-Chih Kuo, Rajendiran Rajesh
Summary: Tumor malignancy poses a serious threat to human survival and lacks a systematic cure. Overexpression of inhibitor of apoptosis protein (IAP) hinders treatment efficacy and increases the difficulty in medication. Innovative strategies using drugs and genes to suppress IAP expression, particularly through polymeric nanoparticles and liposomes, show promising results in accelerating cancer cell apoptosis and retarding tumor propagation. These advancements have great potential for clinical trials in the near future.
JOURNAL OF THE TAIWAN INSTITUTE OF CHEMICAL ENGINEERS
(2022)
Article
Oncology
Karl Knipper, Su Ir Lyu, Heike Goebel, Alexander I. Damanakis, Yue Zhao, Christiane J. Bruns, Thomas Schmidt, Hamid Kashkar, Alexander Quaas, Lars M. Schiffmann, Felix C. Popp
Summary: This study examined the role of XIAP in patients with PDAC in relation to the inflammatory microenvironment. The results showed that XIAP-positive patients had significantly better survival in lymph node-positive subgroups and in T-cell-rich or neutrophil-rich tumors. However, there was no correlation between XIAP expression and survival in the total population.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Oncology
Steven Kregel, Chao Wang, Xin Han, Lanbo Xiao, Ester Fernandez-Salas, Pushpinder Bawa, Brooke L. McCollum, Kari Wilder-Romans, Ingrid J. Apel, Xuhong Cao, Corey Speers, Shaomeng Wang, Arul M. Chinnaiyan
Article
Chemistry, Medicinal
Mingliang Wang, Jianfeng Lu, Mi Wang, Chao-Yie Yang, Shaomeng Wang
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Xinrui Yuan, Hong Bu, Jinpei Zhou, Chao-Yie Yang, Huibin Zhang
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Chemistry, Medicinal
Haibin Zhou, Longchuan Bai, Renqi Xu, Donna McEachern, Krishnapriya Chinnaswamy, Ruiting Li, Bo Wen, Mi Wang, Chao-Yie Yang, Jennifer L. Meagher, Duxin Sun, Jeanne A. Stuckey, Shaomeng Wang
Summary: SD-91 is a potent, highly selective, and efficacious STAT3 degrader that effectively induces degradation of STAT3 protein with high selectivity, demonstrating complete and long-lasting tumor regression in preclinical models. It has the potential for extensive evaluations in the treatment of human cancers and diseases where STAT3 plays a critical role.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Multidisciplinary Sciences
Haibin Zhou, Jianfeng Lu, Krishnapriya Chinnaswamy, Jeanne A. Stuckey, Liu Liu, Donna McEachern, Chao-Yie Yang, Denzil Bernard, Hong Shen, Liangyou Rui, Yi Sun, Shaomeng Wang
Summary: The study identifies two potent and selective covalent DCN1 inhibitors that selectively inhibit cullin-3 neddylation in cells, leading to increased NRF2 protein levels and protection of mice from liver damage.
NATURE COMMUNICATIONS
(2021)
Article
Hematology
Simona Pagliuca, Carmelo Gurnari, Hassan Awada, Ashwin Kishtagari, Sunisa Kongkiatkamon, Laila Terkawi, Misam Zawit, Yihong Guan, Thomas LaFramboise, Babal K. Jha, Bhumika J. Patel, Betty K. Hamilton, Navneet S. Majhail, Sofie Lundgren, Satu Mustjoki, Yogen Saunthararajah, Valeria Visconte, Timothy A. Chan, Chao-Yie Yang, Tobias L. Lenz, Jaroslaw P. Maciejewski
Summary: Idiopathic aplastic anemia (IAA) is a rare autoimmune bone marrow failure disorder. The molecular analysis of HLA complexes in a cohort of IAA patients revealed specific patterns affecting self-presentation and T-cell dysfunction, potentially contributing to the disease pathogenesis and clinical outcomes. Low HED in HLA genotypes was associated with increased risk of malignant progression and worse survival, suggesting reduced tumor surveillance and potential involvement in other autoimmune disorders.
Article
Chemistry, Medicinal
Rohan Kalyan Rej, Changwei Wang, Jianfeng Lu, Mi Wang, Elyse Petrunak, Kaitlin P. Zawacki, Donna McEachern, Chao-Yie Yang, Lu Wang, Ruiting Li, Krishnapriya Chinnaswamy, Bo Wen, Duxin Sun, Jeanne A. Stuckey, Yunlong Zhou, Jianyong Chen, Guozhi Tang, Shaomeng Wang
Summary: The discovery of exceptionally potent and efficacious EED inhibitors has demonstrated significant potential for the treatment of human cancers and other diseases. Through optimization and structural studies, a promising compound, EEDi-5273, has shown excellent inhibitory effects on tumor growth in experiments.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Rajib Bhuniya, Xinrui Yuan, Longchuan Bai, Kathryn L. Howie, Rui Wang, Wei Li, Frank Park, Chao-Yie Yang
Summary: CDC20 overexpression is associated with poor prognosis in breast and other cancers. By designing new CDC20 inhibitors and improving their chemical structure, the antitumor activity can be enhanced. The most effective inhibitor, 22, shows promise for further development.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Hematology
Upendra Mahat, Bhavuk Garg, Chao-Yie Yang, Hrishikesh Mehta, Rabi Hanna, Heesun J. Rogers, Aron Flagg, Andrei I. Ivanov, Seth J. Corey
Summary: This study describes a new gene involved in granulopoiesis, called LCP1. The study found that mutations in this gene can cause neutropenia and abnormal granulocyte development in children. Additionally, the mutant form of LCP1 leads to aberrant actin dynamics. This research is important for understanding the mechanism of neutropenia caused by abnormal actin regulation.
Article
Chemistry, Physical
Xinrui Yuan, Krishnapriya Chinnaswamy, Jeanne A. Stuckey, Chao-Yie Yang
Summary: Cytokine signaling mediated by cytokine receptors plays a crucial role in immune regulation and diseases. This study demonstrates the inhibition of ST2 and IL33 binding by small molecules containing an aromatic ring and a charged group, suggesting a potential mechanism for modulating extracellular cytokine receptors and cytokine interaction.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Correction
Chemistry, Medicinal
Xinrui Yuan, Kathryn L. Howie, Mona Kazemi Sabzvar, Krishnapriya Chinnaswamy, Jeanne A. Stuckey, Chao-Yie Yang
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Medicinal
Xinrui Yuan, Kathryn L. Howie, Mona Kazemi Sabzvar, Krishnapriya Chinnaswamy, Jeanne A. Stuckey, Chao-Yie Yang
Summary: RNA splicing is a crucial biological process involving the removal of introns and joining of exons to generate mature mRNA. Mutations in splicing factors containing the UHM domain are frequently observed in myeloid neoplasms. Our study aimed to assess the binding activities between UHM domains and ULM peptides, as well as small-molecule inhibitors, to guide the development of selective UHM domain inhibitors in the future.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Medicinal
Madison N. Sluter, Rajib Bhuniya, Xinrui Yuan, Andhavaram Ramaraju, Yu Chen, Ying Yu, Keyur R. Parmar, Zaid H. Temrikar, Ashish Srivastava, Bernd Meibohm, Jianxiong Jiang, Chao-Yie Yang
Summary: Our findings showed that our thiazole-based mPGES-1 inhibitors, UT-11 and compound 19, were able to suppress PGE2 production in human and murine cells. We selected UT-11 for evaluation in a lipopolysaccharide (LPS)-induced inflammation model based on in vitro and in vivo pharmacokinetic data. Our compound significantly suppressed proinflammatory cytokines and chemokines in the hippocampus, indicating its potential in treating neuroinflammatory conditions.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2023)
Article
Chemistry, Medicinal
Canhui Zheng, Rohan Kalyan Rej, Mi Wang, Liyue Huang, Ester Fernandez-Salas, Chao-Yie Yang, Shaomeng Wang
Summary: In this study, a new class of highly potent and reversible LSD1 inhibitors, pyrrolo[2,3-c]pyridines, were discovered. Compound 46 showed significant inhibition of LSD1 enzymatic activity and cell growth, making it a promising lead compound for further optimization.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Physiology
Mallory Swanson, Jiyoung Yun, Daniel M. Collier, Connor Seif, Chao-Yie Yang, Kevin R. Regner, Frank Park
Summary: The expression levels and distribution of CDC20 in the kidney are influenced by injurious stimuli, and inhibiting CDC20 function can alleviate and reverse kidney injury.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2023)