Protein arginine methyltransferases (PRMTs) play important roles in transcription, splicing, DNA damage repair, RNA biology, and cellular metabolism. Thus, PRMTs have been attractive targets for various diseases. In this study, we reported the design and synthesis of a potent pan-inhibitor for PRMTs that tethers a thioadenosine and various substituted guanidino groups through a propyl linker. Compound II757 exhibits a half-maximal inhibition concentration (IC50) value of 5 to 555 nM for eight tested PRMTs, with the highest inhibition for PRMT4 (IC50 = 5 nM). The kinetic study demonstrated that II757 competitively binds at the SAM binding site of PRMT1. Notably, II757 is selective for PRMTs over a panel of other methyltransferases, which can serve as a general probe for PRMTs and a lead for further optimization to increase the selectivity for individual PRMT.
Lymphoma is a cancer arising from B or T lymphocytes that are central immune system components. It is one of the three most common cancers encountered in the canine; lymphoma affects middle-aged to older dogs and usually stems from lymphatic tissues, such as lymph nodes, lymphoid tissue, or spleen. Despite the advance in the management of canine lymphoma, a better understanding of the subtype and tumor aggressiveness is still crucial for improved clinical diagnosis to differentiate malignancy from hyperplastic conditions and to improve decision-making around treating and what treatment type to use. This study aimed to evaluate a potential novel biomarker related to iron metabolism,
... Show MoreAmorphization of drug has been considered as an attractive approach in improving drug solubility and bioavailability. Unlike their crystalline counterparts, amorphous materials lack the long-range order of molecular packing and present the highest energy state of a solid material. Co-amorphous systems (CAM) are an innovative formulation technique by where the amorphous drugs are stabilized via powerful intermolecular interactions by means of a low molecular co-former.
This review highlights the different approaches in the preparation of co-amorphous drug delivery system, the proper selection of the co-formers. In addition, the recent advances in characterization, Industrial scale and formulation will be discussed.
Abstract
Bivariate time series modeling and forecasting have become a promising field of applied studies in recent times. For this purpose, the Linear Autoregressive Moving Average with exogenous variable ARMAX model is the most widely used technique over the past few years in modeling and forecasting this type of data. The most important assumptions of this model are linearity and homogenous for random error variance of the appropriate model. In practice, these two assumptions are often violated, so the Generalized Autoregressive Conditional Heteroscedasticity (ARCH) and (GARCH) with exogenous varia
... Show MoreBackground: Antimicrobial prescribing patterns have an important role in the emergence of resistance, and community pharmacists have a substantial influence on this issue. Objective: To assess community pharmacists' behaviors and attitudes toward antimicrobial dispensing, determine their proportions and categories, and examine the underlying rationales for this practice. Methods: A descriptive cross-sectional survey of community pharmacists in Iraq was conducted from June to August 2023, using a self-administered validated questionnaire. The attitudes, practices, and motivations driving the distribution of antimicrobials without a prescription (AWP) were explored in three areas. Results: A sizable proportion (61.6%) of respondents rejected
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