UNASSIGNED: Cancer is a prominent cause of death globally, triggered by both non-genetic and genetic alterations in genes influenced by various environmental factors. The tetrahydroisoquinoline (THIQ), specifically 1,2,3,4-tetrahydroisoquinoline serves as fundamental element in various alkaloids, prevalent in proximity to quinoline and indole alkaloids.
UNASSIGNED: In this review, the therapeutic applications of THIQ derivatives as an anticancer agent from 2016 to 2024 have been examined. The patents were gathered through comprehensive searches of the Espacenet, Google patent, WIPO, and Sci Finder databases. The therapeutic areas encompassed in the patents include numerous targets of cancer.
UNASSIGNED: THIQ analogues play a crucial role in medicinal chemistry, with many being integral to pharmacological processes and clinical trials. Numerous THIQ compounds have been synthesized for therapeutic purposes, notably in cancer treatment. They show great promise for developing anticancer drugs, demonstrating strong affinity and efficacy against various cancer targets. The creation of multi-target ligands is a compelling avenue for THIQ-based anticancer drug discovery.

UNASSIGNED: Protein arginine methyltransferase 5 (PRMT5) belongs to type II arginine methyltransferases. Since PRMT5 plays an essential role in mammalian cells, it can regulate various physiological functions, including cell growth and differentiation, DNA damage repair, and cell signal transduction. It is an epigenetic target with significant clinical potential and may become a powerful drug target for treating cancers and other diseases.
UNASSIGNED: This review provides an overview of small-molecule inhibitors and their associated combined treatment strategies targeting PRMT5 in cancer treatment patents published since 2018, and also summarizes the progress made by several biopharmaceutical companies in the development, application, and clinical trials of small-molecule PRMT5 inhibitors. The data in this review come from WIPO, UniProt, PubChem, RCSB PDB, National Cancer Institute, and so on.
UNASSIGNED: Many PRMT5 inhibitors have been developed with good inhibitory activities, but most of them lack selectivities and are associated with adverse clinical responses. In addition, the progress was almost all based on the previously established skeleton, and more research and development of a new skeleton still needs to be done. The development of PRMT5 inhibitors with high activities and selectivities is still an essential aspect of research in recent years.

Protein arginine methyltransferases (PRMTs), enzymes catalyzing the methylation of target proteins, play an essential role in maintaining functional homeostasis in normal physiology. Aberrant expressions and enhanced enzymatic activities of PRMTs have been closely associated with pathological states such as cancer, inflammatory, immune, metabolic, and neurodegenerative diseases. Therefore, the development of inhibitors targeting PRMTs has attracted a great deal of attention in both pharmaceutical industries and academic community. This review focuses on the small-molecule inhibitors targeting PRMTs in cancer therapy in the patents published since 2019. The recent clinical development is also discussed here. In recent years, the discovery of small-molecule PRMT inhibitors, especially PRMT5 inhibitors has become a rapidly expanding research area for cancer therapy. Although a number of potent PRMT inhibitors with different chemical scaffolds have been developed and nine of them have entered into clinical trials, their scaffolds are relatively less diverse. Sub-type selectivity should be considered in drug discovery as nonselective inhibition of PRMTs may cause undesirable pharmacological effects. Hence, the development of new effective inhibitors with isoform-specific and tumor-biased distributions remains an important area for further studies.

Protein arginine methyltransferase 5 (PRMT5) inhibitors are a new class of antineoplastic agents showing promising preliminary clinical efficacy. Targeting an enzyme involved in a wide array of cellular and transcriptional pro-oncogenic processes, this class offers multifaceted tumor-suppressive effects. Partial response has been seen in adenoid cystic carcinoma from both GSK3326595 and JNJ-64619178, with four cases of stable disease seen with PRT543. Highly significant is a durable complete response in isocitrate dehydrogenase 1-mutated glioblastoma multiforme with PRT811. Both alone and in combination with existing chemotherapies and immunotherapies, this class shows promising preliminary data, particularly in cancers with splicing mutations and DNA damage repair deficiencies. Further studies are warranted, and there are clinical trials to come whose data will be telling of the efficacy of PRMT5 inhibitors in both hematologic and solid malignancies. The aim of this study is to compile available results of PRMT5 inhibitors in oncology clinical trials.

OBJECTIVE: Since protein arginine methyltransferase 5 (PRMT5) is abnormally expressed in various tumors, in this study we aim to assess the association between PRMT5 and clinicopathological and prognostic features.
METHODS: Electronic databases including PubMed, Web of Science, Scopus, ScienceDirect, and the Cochrane Library were searched until July 25, 2021. The critical appraisal of the eligible studies was performed using the Newcastle-Ottawa Quality Assessment Scale. Pooled hazard ratios (HR) and pooled odds ratios (OR) were calculated to assess the effect. Engauge Digitizer version 12.1, STATA version 15.1, and R version 4.0.5 were used to obtain and analysis the data.
RESULTS: A total of 32 original studies covering 15,583 patients were included. In our data, it indicated that high level of PRMT5 was significantly correlated with advanced tumor stage (OR = 2.12, 95% CI: 1.22-3.70, P =.008; I2 = 80.7%) and positively correlated with poor overall survival (HR = 1.59, 95% CI: 1.46-1.73, P < .001; I2 = 50%) and progression-free survival (HR = 1.53, 95% CI: 1.24-1.88, P < .001; I2 = 0%). In addition, sub-group analysis showed that high level of PRMT5 was associated with poor overall survival for such 5 kinds of cancers as hepatocellular carcinoma, pancreatic cancer, breast cancer, gastric cancer, and lung cancer.
CONCLUSIONS: For the first time we found PRMT5 was pan-cancerous as a prognostic biomarker and high level of PRMT5 was associated with poor prognosis for certain cancers.