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Identification of 8-(2-methyl phenyl)-9H-benzo[f]indeno[2,1-c]quinolin-9-one (C-5635020) as a novel and selective TGFβ RII kinase inhibitor for breast cancer therapy.
Biochem Biophys Res Commun
January 2025
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia. Electronic address:
Objective And Significance: Transforming growth factor-beta (TGF-β) plays a pivotal role in breast development by modulating tissue composition during the developmental phase. The TGFβ type II receptor (TGFβ RII) is implicated in breast cancer and represents a valuable therapeutic target. Due to the off-target side effects of many existing TGFβI/TGFβ RII inhibitors, a more targeted approach to drug discovery is necessary.
View Article and Find Full Text PDFCell-Penetrating Peptide Like Anti-Programmed Cell Death-Ligand 1 Peptide Conjugate-Based Self-Assembled Nanoparticles for Immunogenic Photodynamic Therapy.
ACS Nano
January 2025
BK21 Program, Department of Applied Life Science, Konkuk University, Chungju 27478, Republic of Korea.
The tumor-specific efficacy of the most current anticancer therapeutic agents, including antibody-drug conjugates (ADCs), oligonucleotides, and photosensitizers, is constrained by limitations such as poor cell penetration and low drug delivery. In this study, we addressed these challenges by developing, a positively charged, amphiphilic Chlorin e6 (Ce6)-conjugated, cell-penetrating anti-PD-L1 peptide nanomedicine (CPPD1) with enhanced cell and tissue permeability. The CPPD1 molecule, a bioconjugate of a hydrophobic photosensitizer and strongly positively charged programmed cell death-ligand 1 (PD-L1) binding cell-penetrating peptide (CPP), is capable of self-assembling into nanoparticles with an average size of 199 nm in aqueous solution without the need for any carriers.
View Article and Find Full Text PDFTargeting KAT6A/B as a New Therapeutic Strategy for Cancer Therapy.
J Med Chem
January 2025
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
The lysine acetyltransferase 6A (KAT6A, MOZ, MYST3) is a member of the MYST family of protein acetyltransferases, which are essential for different biological processes such as craniofacial, embryonic, stem cell development, and hematopoiesis. KAT6A is an oncogene in human acute myeloid leukemia (AML), and KAT6A overexpression in AML is associated with metastases and poor prognoses. Furthermore, KAT6A mutations play an important role in cancer formation and progression and result in therapeutic resistance in both hematopoietic malignancies and solid tumors.
View Article and Find Full Text PDFIsoferulic acid facilitates effective clearance of hypervirulent Klebsiella pneumoniae through targeting capsule.
PLoS Pathog
January 2025
Department of Respiratory Medicine, Center for Pathogen Biology and Infectious Diseases, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun, China.
Hypervirulent Klebsiella pneumoniae (hvKP) poses an alarming threat in clinical settings and global public health owing to its high pathogenicity, epidemic success and rapid development of drug resistance, especially the emergence of carbapenem-resistant lineages (CR-hvKP). With the decline of the "last resort" antibiotic class and the decreasing efficacy of first-line antibiotics, innovative alternative therapeutics are urgently needed. Capsule, an essential virulence determinant, is a major cause of the enhanced pathogenicity of hvKP and represents an attractive drug target to prevent the devastating clinical outcomes caused by hvKP infection.
View Article and Find Full Text PDFAn Acetylcholine M1 Receptor-Positive Allosteric Modulator (TAK-071) in Parkinson Disease With Cognitive Impairment: A Phase 2 Randomized Clinical Trial.
JAMA Neurol
January 2025
Takeda Development Center Americas, Inc, Cambridge, Massachusetts.
Importance: Fall risk and cognitive impairment are prevalent and burdensome in Parkinson disease (PD), requiring efficacious, well-tolerated treatment.
Objective: To evaluate the safety and efficacy of TAK-071, a muscarinic acetylcholine M1 positive allosteric modulator, in participants with PD, increased fall risk, and cognitive impairment.
Design, Setting, And Participants: This phase 2 randomized double-blind placebo-controlled crossover clinical trial was conducted from October 21, 2020, to February 27, 2023, at 19 sites in the US.
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