The discovery and exploitation of new drug targets is a key focus for both the pharmaceutical industry and academic biomedical research. To provide an insight into trends in the exploitation of new drug targets, we have analysed the drugs that were approved by the US Food and Drug Administration during the past three decades and examined the interactions of these drugs with therapeutic targets that are encoded by the human genome, using the DrugBank database and extensive manual curation. We have identified 435 effect-mediating drug targets in the human genome, which are modulated by 989 unique drugs, through 2,242 drug-target interactions. We also analyse trends in the introduction of drugs that modulate previously unexploited targets, and discuss the network pharmacology of the drugs in our data set.
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http://dx.doi.org/10.1038/nrd3478 | DOI Listing |
J Transl Med
January 2025
Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China.
Background: Psoriasis is a common chronic, recurrent, immune-mediated disease involved in the skin or joints or both. However, deeper insight into the genetic susceptibility of psoriasis is still unclear.
Methods: Here we performed the largest multi-ancestry meta-analysis of genome-wide association study including 28,869 psoriasis cases and 443,950 healthy controls.
J Transl Med
January 2025
Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
Background: Drug resistance constitutes one of the principal causes of poor prognosis in breast cancer patients. Although cancer cells can maintain viability independently of mitochondrial energy metabolism, they remain reliant on mitochondrial functions for the synthesis of new DNA strands. This dependency underscores a potential link between mitochondrial energy metabolism and drug resistance.
View Article and Find Full Text PDFMol Med
January 2025
Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, 8174673461, Iran.
Acute myeloid leukemia (AML) is caused by altered maturation and differentiation of myeloid blasts, as well as transcriptional/epigenetic alterations, all leading to excessive proliferation of malignant blood cells in the bone marrow. Tumor heterogeneity due to the acquisition of new somatic alterations leads to a high rate of resistance to current therapies or reduces the efficacy of hematopoietic stem cell transplantation (HSCT), thus increasing the risk of relapse and mortality. Single-cell RNA sequencing (scRNA-seq) will enable the classification of AML and guide treatment approaches by profiling patients with different facets of the same disease, stratifying risk, and identifying new potential therapeutic targets at the time of diagnosis or after treatment.
View Article and Find Full Text PDFNat Commun
January 2025
Olivia Newton-John Cancer Research Institute, Heidelberg, Melbourne, Australia.
Cas12a is a next-generation gene editing tool that enables multiplexed gene targeting. Here, we present a mouse model that constitutively expresses enhanced Acidaminococcus sp. Cas12a (enAsCas12a) linked to an mCherry fluorescent reporter.
View Article and Find Full Text PDFNat Commun
January 2025
College of Pharmaceutical Sciences, National Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang University, Hangzhou, China.
Nicotinamide (NAM), a main precursor of NAD+, is essential for cellular fuel respiration, energy production, and other cellular processes. Transporters for other precursors of NAD+ such as nicotinic acid and nicotinamide mononucleotide (NMN) have been identified, but the cellular transporter of nicotinamide has not been elucidated. Here, we demonstrate that equilibrative nucleoside transporter 1 and 2 (ENT1 and 2, encoded by SLC29A1 and 2) drive cellular nicotinamide uptake and establish nicotinamide metabolism homeostasis.
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