Considering that natural products as tyrosinase inhibitors are considered to be safe, with little or no toxic side effects and friendly to the environment, it is urgent to develop a new recognition strategy for natural tyrosinase inhibitors. In current study, an integrated computational analysis was conducted on Cys-containing dipeptides with high tyrosinase inhibitory activity. Firstly, molecular fingerprint similarity (FS) clustering analysis was performed on the target molecule using machine learning. Secondly, genetic algorithm was used to construct two kinds of highly accurate QSAR models (R² = .978 and .984, respectively) with Cys at C-terminal and N-terminal. Finally, three novel natural candidate inhibitors (NP1, NP2, NP3) were discovered using Molnatsim natural product cluster library, automated screening process and QSAR based on the maximum common substructure (MCS) algorithm, their IC_50pre were 260.96, 3.37 and 0.05 μm/mol. Pharmacokinetic predictions showed that NP2 and NP3 had high Bioavailability Score (BS) and Gastrointestinal (GI) absorption, and molecular dynamics simulations further validated the stability of these novel natural candidate inhibitors in binding to tyrosinase. In conclusion, our results provide new ideas for discovering new activities of natural products, and provide an accurate QSAR model for developing novel tyrosinase inhibitors based on MCS Cys-containing dipeptides. PRACTICAL APPLICATIONS: Tyrosinase is related to the occurrence of diseases such as excessive melanin deposition such as freckles and chloasma, and studies have shown that neurodegeneration associated with Parkinson's disease and Huntington's disease is also related. In addition, enzymatic browning on the surface of fresh fruit and vegetable slices will shorten the shelf life and affect their quality. Therefore, screening, designing and developing efficient tyrosinase inhibitors is very important in the fields of medicine, cosmetics, food and so on.

28 Aug 2022·British Journal of Nutrition

Nutrient patterns are associated with discordant apoB and LDL: a population-based analysis

Article

Author: Shekoohi, Niloofar ; George, Elena S ; Lovegrove, Julie A ; Webb, Richard J ; Davies, Ian G ; Mazidi, Mohsen

AbstractIndividuals with discordantly high apoB to LDL-cholesterol levels carry a higher risk of atherosclerotic CVD compared with those with average or discordantly low apoB to LDL-cholesterol. We aimed to determine associations between apoB and LDL-cholesterol discordance in relation to nutrient patterns (NP) using National Health and Nutrition Examination Survey data. Participants were grouped by established LDL-cholesterol and apoB cut-offs (Group 1: low apoB/low LDL-cholesterol, Group 2: low apoB/high LDL-cholesterol, Group 3: high apoB/low LDL-cholesterol, Group 4: high apoB/high LDL-cholesterol). Principle component analysis was used to define NP. Machine learning (ML) and structural equation models were applied to assess associations of nutrient intake with apoB/LDL-cholesterol discordance using the combined effects of apoB and LDL-cholesterol. Three NP explained 63·2 % of variance in nutrient consumption. These consisted of NP1 rich in SFA, carbohydrate and vitamins, NP2 high in fibre, minerals, vitamins and PUFA and NP3 rich in dietary cholesterol, protein and Na. The discordantly high apoB to LDL-cholesterol group had the highest consumption of the NP1 and the lowest consumption of the NP2. ML showed nutrients that had the greatest unfavourable dietary contribution to individuals with discordantly high apoB to LDL-cholesterol were total fat, SFA and thiamine and the greatest favourable contributions were MUFA, folate, fibre and Se. Individuals with discordantly high apoB in relation to LDL-cholesterol had greater adherence to NP1, whereas those with lower levels of apoB, irrespective of LDL-cholesterol, were more likely to consume NP3.

01 Dec 2019·Drug Delivery and Translational ResearchQ3 · MEDICINE

Chlorpheniramine maleate containing chitosan-based nanoparticle-loaded thermosensitive in situ gel for management in allergic rhinitis

Q3 · MEDICINE

Article

Author: Joshi, Monika ; Malik, Anuj ; Kumar, Manish ; Bhatt, Shailendra ; Shankar, Ravi ; Upadhayay, Pooja

The aim of the present study was to fabricate a thermosensitive gel containing chlorpheniramine maleate (CPM)-loaded nanoparticles following intranasal administration for effective treatment of allergic rhinitis. Chitosan-based nanoparticles were prepared by a precipitation method followed by the addition of developed NPs within the poloxamer 407- and carbopol 934P-based mucoadhesive thermoreversible gel. Developed formulations were evaluated for particle size, PDI, % entrapment efficiency, and % cumulative drug permeation. NP3 formulation was found to be optimized on the basis of minimum particle size (143.9 nm), maximum entrapment efficiency (80.10 ± 0.414%), and highest drug permeation (90.92 ± 0.531%). The optimized formulation NP3 was then formulated into thermoreversible in situ gel. This intensifies the contact between the nasal mucosa and the drug and increases and facilitates the drug absorption which results in increased bioavailability. G4 formulation was selected as the optimized formulation on the basis of gelation ability and mucoadhesive strength. Histology was carried out to examine the damage caused by the optimized G4 formulation. Results revealed no visual signs of tissue damage thus indicated safe nasal delivery of nanoparticulate in situ gel formulation G4. Thus, intranasal CPM NP-loaded in situ gel was found to be a promising formulation for the management of allergic rhinitis.

100 Deals associated with NP-3

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Cystinosis	Phase 1	AU	Nacuity Pharmaceuticals, Inc.Startup	20 Jul 2020

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

NP-3

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation