Article
Biology
Jingyi Tang, Patrick J. Casey, Mei Wang
Summary: DNA damage has a dual impact on cancer cells: inducing genomic instability to promote cancer development while compromising proliferation and survival. Inhibiting ICMT reduces MAPK signaling activity, impairs DNA damage repair machinery, leading to cell cycle arrest and apoptosis in cancer cells. ICMT inhibition transforms cancer cells into a BRCA-like state, sensitizing them to PARP inhibitor and other DNA-damaging agents, particularly in anchorage-independent or in vivo conditions.
LIFE SCIENCE ALLIANCE
(2021)
Article
Andrology
Xiaodan Teng, Yang Liu, Liping Wang, Guonian Wang
Summary: The study found that lidocaine exerts anti-tumor effects in bladder cancer by down-regulating the expression of ICMT, and that high expression of ICMT is closely related to the clinical phenotype of bladder cancer. In addition, lidocaine treatment significantly inhibited the proliferation of bladder cancer cells, promoted apoptosis, and inhibited tumor growth.
TRANSLATIONAL ANDROLOGY AND UROLOGY
(2021)
Article
Oncology
Weifeng Wan, Wenfeng Xiao, Wen Pan, Ligang Chen, Zhiyong Liu, Jianguo Xu
Summary: This study demonstrates that the upregulation of ICMT expression is associated with glioblastoma, and its pharmacological inhibitors effectively suppress glioblastoma growth and act synergistically with chemotherapy drugs. Therefore, ICMT represents a promising target for the treatment of glioblastoma.
CANCER CHEMOTHERAPY AND PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Jiguo Xie, Xiaofei Zhao, Peng Zhang, Yueyue Zhang, Ru Cheng, Zhiyuan Zhong, Chao Deng
Summary: This study adopts phenylboronic acid-functionalized polypeptide nanovehicles for co-delivery of BCL2 (ABT199) and MCL1 (TW37) inhibitors to achieve synergistic and potent treatment of AML. The nanovehicles exhibit efficient and robust drug coencapsulation using dynamic boronic ester bonds, B-N coordination, and pi-pi stacking. In both mouse and cell models, the nanoparticles show significant anti-tumor activity and hold great potential for AML treatment.
Article
Biochemistry & Molecular Biology
Qiang Qiu, Yuanyuan Sun, Linyu Yang, Qingqing Li, Yunyu Feng, Mengyuan Li, Yuexia Yin, Li Zheng, Ning Li, Huandi Qiu, Xue Cui, Wei He, Bochuan Wang, Cong Pan, Zi Wang, Juan Huang, Klarke M. M. Sample, Zhihui Li, Yiguo Hu
Summary: We have identified TSPAN32 as a key factor in the development of Philadelphia chromosome-positive (Ph+) leukemia. BCR-ABL suppresses the expression of TSPAN32, while ectopic expression of TSPAN32 inhibits the proliferation of Ph+ cell lines upon Imatinib treatment. Overexpression of TSPAN32 in a murine model significantly hinders the progression of BCR-ABL-induced leukemia and impairs the proliferation of leukemia stem cells (LSCs). These findings suggest that targeting TSPAN32 and the associated signaling axis may provide a novel therapeutic strategy for CML treatment.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Qiuping Xiang, Tianbang Wu, Cheng Zhang, Chao Wang, Hongrui Xu, Qingqing Hu, Jiankang Hu, Guolong Luo, Xiaoxi Zhuang, Xishan Wu, Yan Zhang, Yong Xu
Summary: This study reports the discovery of a 1-(indolizin-3-yl)ethan-1-one derivative as a potent and selective CBP bromodomain inhibitor for AML drug development.
BIOORGANIC CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Atsunori Kaneshige, Longchuan Bai, Mi Wang, Donna McEachern, Jennifer L. Meagher, Renqi Xu, Paul D. Kirchhoff, Bo Wen, Duxin Sun, Jeanne A. Stuckey, Shaomeng Wang
Summary: We discovered a potent and selective STAT5 degrader with strong antitumor activity in vivo. Using PROTAC technology, we transformed small-molecule ligands into selective STAT5 degraders, with AK-2292 as the best compound. AK-2292 effectively induced degradation of STAT5 proteins in AML cell lines and showed strong antitumor activity in mice.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Alberto Blanco Sanchez, Rodrigo Gil Manso, Gonzalo Carreno-Tarragona, Diana Paredes Ruiz, Jesus Gonzalez Olmedo, Joaquin Martinez-Lopez, Carmen Diaz Pedroche, Rosa Ayala
Summary: This study demonstrates the importance of assessing cardiovascular risk and effectively managing risk factors in patients with CML treated with tyrosine kinase inhibitors. Follow-up in a specialized cardiovascular risk consultation can lead to a reduction in cardiovascular adverse events and improve patients' overall cardiovascular health.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Hematology
Zhi Wen, Grant Yun, Alexander Hebert, Guangyao Kong, Erik A. Ranheim, Remington Finn, Adhithi Rajagoplan, Shuyi Li, Yun Zhou, Mei Yu, Alisa Damnernsawad, Jeroen P. Roose, Joshua J. Coon, Renren Wen, Demin Wang, Jing Zhang
Summary: ETP-ALL is characterized by hyperactivation of cytokine receptor/Ras signaling, with downregulation of WT KRAS and Rasgrp1 serving as negative regulators of Ras/ERK pathway, contributing to cell proliferation in oncogenic Nras-driven ETP-like leukemia.
Article
Pharmacology & Pharmacy
Tingting Lu, Jiangyan Cao, Fengming Zou, Xixiang Li, Aoli Wang, Wenliang Wang, Huamin Liang, Qingwang Liu, Chen Hu, Cheng Chen, Zhenquan Hu, Wenchao Wang, Lili Li, Jian Ge, Yang Shen, Tao Ren, Jing Liu, Ruixiang Xia, Qingsong Liu
Summary: CHMFL-48 is a novel type II kinase inhibitor that potently inhibits the wild-type BCR-ABL kinase and a panel of imatinib-resistant mutants. This drug shows strong inhibitory activity in a cellular context, blocking autophosphorylation of BCR-ABL kinase, affecting downstream signaling mediators, and inducing cell cycle progression blockade and apoptosis.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yu-Jun Dai, Si-Yuan He, Fang Hu, Xue-Ping Li, Jian-Ming Zhang, Si-Liang Chen, Wei-Na Zhang, Hai-Min Sun, Da-Wei Wang
Summary: The proportion of NK cells in the bone marrow could predict the prognosis of ND-AML patients, and combination of MCL1 inhibitor with NK cell-based immunotherapy could effectively improve therapeutic efficiency.
Article
Multidisciplinary Sciences
Shikha Nayar, Joshua K. Morrison, Mamta Giri, Kyle Gettler, Ling-Shiang Chuang, Laura A. Walker, Huaibin M. Ko, Ephraim Kenigsberg, Subra Kugathasan, Miriam Merad, Jaime Chu, Judy H. Cho
Summary: NOD2 deficiency contributes to fibrosis and stricturing complications in Crohn's disease through dysregulated homeostasis of activated fibroblasts and macrophages, which can be ameliorated by gp130 blockade. Carriers of NOD2 risk alleles exhibit dysregulated homeostasis of activated fibroblasts and macrophages, suggesting a potential role for gp130 blockade in rescuing the activated program caused by NOD2 mutations.
Article
Pharmacology & Pharmacy
Yahong Liu, Ying Cheng, Gongchao Huang, Xiangying Xia, Xingkai Wang, Hongqi Tian
Summary: Tunlametinib is a novel MEK inhibitor with higher selectivity and anti-proliferation activity compared to current MEK inhibitors. It exhibits significant tumor suppression and cell cycle regulation in vivo. Furthermore, combination therapy of tunlametinib with other inhibitors or chemotherapeutic agents enhances the treatment response.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Peng Zhao, Linghang Zhuang, Xiangzhu Wang, Song Huang, Heping Wu, Yu Zhou, Yuna Yan, Fan Zhang, Ru Shen, Jing Li, Suxing Liu, Rumin Zhang, Ping Dong, Yuchang Mao, Yuanmin Fan, Chunyong He, Jiakang Sun, Lei Zhang, Qiyue Hu, Hong Wan, Jun Feng, Chang Bai, Feng He, Weikang Tao
Summary: A molecule called SHR902275 (or molecule 33) has been discovered with significantly improved potency and solubility, which shows potential for targeting cancers with mutant RAS and wild type RAF activity. In vivo experiments have demonstrated dose dependent efficacy of molecule 33.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Daniela Damiani, Mario Tiribelli
Summary: The prognosis of acute myeloid leukemia (AML) remains unsatisfactory due to poor response to therapy or relapse, which can be attributed to the over-expression of multidrug resistance (MDR) proteins. ABCG2, an efflux transporter responsible for inducing MDR in leukemic cells, has the ability to extrude many antineoplastic drugs, leading to AML resistance and/or relapse. This review focuses on the expression and role of ABCG2, as well as its regulation and potential inhibition to counteract drug resistance and improve outcomes in AML patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Alba Angelina, Mario Perez-Diego, Jacobo Lopez-Abente, Beate Ruckert, Ivan Nombela, Mubeccel Akdis, Mar Martin-Fontecha, Cezmi Akdis, Oscar Palomares
Summary: Cannabinoids have been found to promote tolerogenic dendritic cells and generate functional FOXP3(+) Tregs, demonstrating immunomodulatory effects in different inflammatory diseases. The mechanism involves metabolic rewiring towards increased mitochondrial activity and oxidative phosphorylation through the activation of CB1 and PPAR alpha.
MUCOSAL IMMUNOLOGY
(2022)
Article
Allergy
Alba Angelina, Rodrigo Jimenez-Saiz, Mario Perez-Diego, Angel Maldonado, Beate Ruckert, Mubeccel Akdis, Mar Martin-Fontecha, Cezmi A. Akdis, Oscar Palomares
Summary: The synthetic cannabinoid WIN55212-2 has anti-inflammatory properties and can intervene in the sensitization process of peanut allergy, promoting tolerogenic responses. This finding provides new possibilities for the development of preventive and therapeutic strategies for peanut allergy.
CLINICAL AND EXPERIMENTAL ALLERGY
(2022)
Article
Biochemistry & Molecular Biology
Maria Raics, Alex Kalman Balogh, Chandan Kishor, Istvan Timari, Francisco J. Medrano, Antonio Romero, Rob Marc Go, Helen Blanchard, Laszlo Szilagyi, Katalin E. Kover, Krisztina Feher
Summary: In this study, the binding affinities of two selenium-containing hGal-3 inhibitors to hGal-3 were investigated using NMR spectroscopy and fluorescence anisotropy titrations. The results showed that these derivatives bind to hGal-3 at a specific site, but with weaker interaction strength.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Dolores Linde, Elena Santillana, Elena Fernandez-Fueyo, Alejandro Gonzalez-Benjumea, Juan Carro, Ana Gutierrez, Angel T. Martinez, Antonio Romero
Summary: This study successfully crystallized two UPO enzymes, rMroUPO and rCviUPO, from different fungal groups through sequence optimization and Escherichia coli expression, revealing their crystal structures and dimeric protein characteristics.
Article
Chemistry, Medicinal
Nora Khiar-Fernandez, Debora Zian, Henar Vazquez-Villa, R. Fernando Martinez, Andrea Escobar-Pena, Roman Foronda-Sainz, Manisha Ray, Maria Puigdomenech-Poch, Giovanni Cincilla, Melchor Sanchez-Martinez, Yasuyuki Kihara, Jerold Chun, Ruben Lopez-Vales, Maria L. Lopez-Rodriguez, Silvia Ortega-Gutierrez
Summary: Spinal cord injuries permanently disrupt spinal connectivity and cause neurological disabilities. Current treatments are limited, so inhibiting the LPA(2) receptor has emerged as a potential therapeutic strategy for reducing SCI-associated damage. A new series of LPA(2) antagonists, including compound 54 (UCM-14216), showed efficacy in an in vivo mouse model, confirming the potential of LPA(2) inhibition for treating SCI.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Jose M. Andreu, Sonia Huecas, Lidia Araujo-Bazan, Henar Vazquez-Villa, Mar Martin-Fontecha
Summary: The global spread of bacterial antimicrobial resistance has created an urgent need for developing new antibiotics. Inhibition of bacterial cell division by targeting the key protein FtsZ, which organizes division in most bacteria, has shown potential. However, developing effective FtsZ-targeting antibiotics has proven challenging. This review discusses research on small molecule inhibitors of bacterial division, focusing on methods to characterize synthetic inhibitors and the potential for discovering new FtsZ-targeting antibiotics.
Review
Biochemistry & Molecular Biology
Pedro Aguilar-Garrido, Alvaro Otero-Sobrino, Miguel Angel Navarro-Aguadero, Maria Velasco-Estevez, Miguel Gallardo
Summary: Hematological malignancies present a challenge due to treatment resistance. RNA-binding proteins have been identified as potential biomarkers and therapeutic targets, and understanding their regulatory mechanisms can help in identifying novel therapeutic approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Bellinda Benhamu, Mar Martin-Fontecha, Henar Vazquez-Villa, Maria L. Lopez-Rodriguez, Silvia Ortega-Gutierrez
Summary: Aging, considered a major risk factor for chronic diseases, is being questioned by recent research that suggests removing senescent cells can ameliorate aging phenotype and associated diseases. This opens the door to tailored therapeutic interventions for extending healthspan and treating aging as a chronic disease.
Article
Oncology
Ana Jimenez-Ubieto, Maria Poza, Alejandro Martin-Munoz, Yanira Ruiz-Heredia, Sara Dorado, Gloria Figaredo, Juan Manuel Rosa-Rosa, Antonia Rodriguez, Carmen Barcena, Laura Parrilla Navamuel, Jaime Carrillo, Ricardo Sanchez, Laura Rufian, Alexandra Juarez, Margarita Rodriguez, Chongwu Wang, Paula de Toledo, Carlos Grande, Manuela Mollejo, Luis-Felipe Casado, Maria Calbacho, Tycho Baumann, Inmaculada Rapado, Miguel Gallardo, Pilar Sarandeses, Rosa Ayala, Joaquin Martinez-Lopez, Santiago Barrio
Summary: In this study, we screened follicular lymphoma patients for liquid biopsy MRD biomarkers using NGS panel and found trackable mutations in a majority of the samples. We used ultra-deep sequencing to track these mutations in follow-up samples and found that positive LiqBio-MRD correlated with a higher risk of progression during treatment. The combination of LiqBio-MRD and PET/CT provided a sensitive and specific identification of patients who progressed in less than two years. This non-invasive approach should be considered in future clinical trials.
Article
Oncology
Larissa Haertle, Natalia Buenache, Hipolito Nicolas Cuesta Hernandez, Michal Simicek, Renata Snaurova, Inmaculada Rapado, Nerea Martinez, Nieves Lopez-Munoz, Jose Maria Sanchez-Pina, Umair Munawar, Seungbin Han, Yanira Ruiz-Heredia, Rafael Colmenares, Miguel Gallardo, Margarita Sanchez-Beato, Miguel Angel Piris, Mehmet Kemal Samur, Nikhil C. Munshi, Rosa Ayala, Klaus Martin Kortum, Santiago Barrio, Joaquin Martinez-Lopez
Summary: Compared to other neoplasias, Multiple Myeloma is highly responsive to proteasome inhibitors due to its sensitivity to changes in protein homeostasis. Genetic alterations of PSMC genes affect the susceptibility of Multiple Myeloma to proteasome inhibitors, playing a significant role in disease development and resistance. These alterations can serve as biomarkers to predict and monitor patient response, guiding treatment decisions.
Review
Biochemistry & Molecular Biology
Juan Kochen Rossi, Cristina Nuevo-Tapioles, Mark R. Philips
Summary: RAS proteins are small GTPases that transmit signals regulating growth and differentiation. KRAS, among the three RAS genes, is the most frequently mutated oncogene in human cancer. It has two splice variants, KRAS4A and KRAS4B, which encode proto-oncoproteins differing mainly in their C-terminal hypervariable regions. KRAS4A has non-overlapping functions with KRAS4B and has been found to play a role in tumors, such as specific regulation of hexokinase I.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Editorial Material
Biochemistry & Molecular Biology
Silvia Ortega-Gutierrez
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Antonio Garcia-Espana, Mark R. R. Philips
Summary: KRAS, HRAS and NRAS proto-oncogenes belong to a family of highly homologous genes encoding small GTPases. KRAS is the ancestral RAS gene and its duplication generated HRAS, while a second duplication of HRAS generated NRAS. Another RAS gene, KRASBL, is absent in mammals and birds. The evolutionary conservation of these RAS isoforms indicates differential functions.
Review
Biochemistry & Molecular Biology
Alvaro Otero-Sobrino, Pablo Blanco-Carlon, Miguel Angel Navarro-Aguadero, Miguel Gallardo, Joaquin Martinez-Lopez, Maria Velasco-Estevez
Summary: Mechanosensitive ion channels play a crucial role in sensing mechanical changes and regulating cellular functions, with significant implications for cancer research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)