CDPBC: A Software Application for Estimation of Concentration Dependent Plasma Binding Capacity of Small Molecule

2018 ◽  
Vol 37 (8) ◽  
pp. 1800007
Author(s):  
Om Prakash ◽  
Upendra Nath Dwivedi
Keyword(s):  
Small Molecule ◽  
Binding Capacity ◽  
Plasma Binding ◽  
Software Application

scholarly journals Thalidomide-based inhibitor for TNF-α: designing and Insilico evaluation

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Biradar Shivaleela ◽  
S. C. Srushti ◽  
S. J. Shreedevi ◽  
R. L. Babu
Keyword(s):  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Inflammatory Diseases ◽  
Binding Capacity ◽  
Preliminary Investigation ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Monocytes And Macrophages ◽  
Potential Ligand

Abstract Background Inflammatory diseases are the vast array of disorders caused by inflammation. During most inflammatory events, many cytokines expressions were modulated, and one such cytokine is tumor necrosis factor-alpha (TNF-α). TNF-α is mainly secreted by monocytes and macrophages. Notably, it has been proposed as a therapeutic target for several diseases. The anti-TNF biology approach is mainly based on monoclonal antibodies. The fusion protein and biosimilars are prevalent in treating inflammation for decades. Only a few small molecule inhibitors are available to inhibit the expression of TNF-α, and one such promising drug was thalidomide. Therefore, the study was carried out to design thalidomide-based small molecule inhibitors for TNF-α. The main objective of our study is to design thalidomide analogs to inhibit TNF-α using the insilico approach. Results Several thalidomide analogs were designed using chemsketch. After filtration of compounds through ‘Lipinski rule of 5’ by Molinspiration tool, as a result, five compounds were selected. All these compounds were subjected to molecular docking, and the study showed that all five compounds had good binding energy. However, based on ADMET predictions, two compounds (S3 and S5) were eliminated. Conclusions Our preliminary results suggest that S1, S2, S4 compounds showed potential ligand binding capacity with TNF-α and, interestingly, with limited or no toxicity. Our preliminary investigation and obtained results have fashioned more interest for further in vitro studies.

In-silico Inhibitory Study of cFos-cJun Complex by T-5224 Based Small Molecule Analogs

2020 ◽  
Vol 17 ◽  
Author(s):  
Srushti Chavadapur ◽  
Shivaleela Biradar ◽  
Babu R. L.
Keyword(s):  
Small Molecule ◽  
Bacterial Infections ◽  
Inflammatory Diseases ◽  
Binding Capacity ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Cell Matrix ◽  
Polypeptide Hormones ◽  
Potential Ligand ◽  
Cell Matrix Interactions

Background:: Inflammatory diseases are one of the major concerns of today’s world, major disorders caused by inflammation includes, allergy, asthma, arthritis, hepatitis, autoimmune diseases, celiac disease etc. During most of these events, many protein and molecules expression were modulated and one such protein is AP-1 (c-Fos-c-Jun heterodimer complex). AP-1 is a dimeric protein activated by several physiological stimuli and environmental insults such as growth factors, polypeptide hormones, neurotransmitters, cytokines, cell-matrix interactions, UV irradiations, viral and bacterial infections. Objective:: Present study is mainly focus on designing of small molecule analogs to inhibit c-Fos-c-Jun complex, as the complex is involved in many inflammatory diseases and precisely involved in disease progression. Therefore, it had been considered as therapeutic target since more than a decade. Methods:: In the present study, an attempt was made to design the analogs of referral drug T-5224. 31 analogs of T-5224 were designed by chemoinformatics approach and subjected to ADMETox for screening. Results and Discussion:: Among the 16 compounds were found to pass the evaluation, all 16 compounds passed the toxicity evaluation except 7th molecule. The molecular docking study showed that the compounds 1, 2 and 16 were having high inhibition constant. Conclusion:: The preliminary results suggest the compounds 1, 2 and 16 are having the potential ligand binding capacity with cFos-cJun complex. Further analysis, with advanced tools, may results in potential small molecule to inhibit the c-Fosc- Jun complex.

Alterations in steroid binding plasma proteins in Macaca nemestrina during pregnancy.

1978 ◽  
Vol 234 (5) ◽  
pp. E489 ◽  
Author(s):  
H S Schiller ◽  
R A Holm ◽  
G P Sackett
Keyword(s):  
Plasma Proteins ◽  
Binding Capacity ◽  
Macaca Nemestrina ◽  
Sex Steroid ◽  
Plasma Binding ◽  
Human Beings ◽  
Binding Characteristics ◽  
Corticosteroid Binding Globulin ◽  
Physiologic Function ◽  
Steroid Binding

We measured the corticosterone and dihydrotestosterone steroid binding capacities of corticosteroid-binding globulin (CBG) and sex steroid plasma binding protein (SBP) throughout pregnancy in seven Macaca nemestrina. The nSBP binding capacity rises significantly by 28 days of pregnancy, remains elevated through 56 days, tends to fall through midpregnancy, and then decreases dramatically to very low values 130-153 days after conception. In contrast, nCBG rises slightly (1.2-fold) in early pregnancy, is elevated in midpregnancy, but is similar to nonpregnant values during the last trimester of pregnancy. Our data indicate that factors controlling the plasma concentration of nCBG and nSBP are not identical. The results are in sharp contrast to those observed in human pregnancies in which both hSBP and hCBG are increased severalfold during pregnancy, including at term. Because the changes of nCBG and nSBP during pregnancy do not paralle the changes observed in human beings even though their steroid binding characteristics are similar, the M. nemestrina may serve as a valuable model for defining the physiologic function of SBP and CBG and the mechanism(s) controlling their concentrations in blood.

A privileged ternary blend enabling non-fullerene organic photovoltaics with over 14% efficiency

2020 ◽  
Vol 8 (43) ◽  
pp. 15135-15141
Author(s):  
Jing Yan ◽  
Yuan-Qiu-Qiang Yi ◽  
Jianqi Zhang ◽  
Huanran Feng ◽  
Yanfeng Ma ◽  
...  
Keyword(s):  
Small Molecule ◽  
Organic Photovoltaics ◽  
Power Conversion ◽  
Ternary Blend ◽  
Conversion Efficiencies

Two non-fullerene small molecule acceptors, NT-4F and NT-4Cl, were designed and synthesized. Power conversion efficiencies of 11.44% and 14.55% were achieved for NT-4Cl-based binary and ternary devices, respectively.

Metallic prions

2004 ◽  
Vol 71 ◽  
pp. 193-202 ◽  
Author(s):  
David R Brown
Keyword(s):  
Prion Protein ◽  
Binding Capacity ◽  
Normal Function ◽  
Transmissible Spongiform Encephalopathies ◽  
Published Data ◽  
Normal Brain ◽  
Copper Binding ◽  
Loss Of Function ◽  
Spongiform Encephalopathies ◽  
The Brain

Prion diseases, also referred to as transmissible spongiform encephalopathies, are characterized by the deposition of an abnormal isoform of the prion protein in the brain. However, this aggregated, fibrillar, amyloid protein, termed PrPSc, is an altered conformer of a normal brain glycoprotein, PrPc. Understanding the nature of the normal cellular isoform of the prion protein is considered essential to understanding the conversion process that generates PrPSc. To this end much work has focused on elucidation of the normal function and activity of PrPc. Substantial evidence supports the notion that PrPc is a copper-binding protein. In conversion to the abnormal isoform, this Cu-binding activity is lost. Instead, there are some suggestions that the protein might bind other metals such as Mn or Zn. PrPc functions currently under investigation include the possibility that the protein is involved in signal transduction, cell adhesion, Cu transport and resistance to oxidative stress. Of these possibilities, only a role in Cu transport and its action as an antioxidant take into consideration PrPc's Cu-binding capacity. There are also more published data supporting these two functions. There is strong evidence that during the course of prion disease, there is a loss of function of the prion protein. This manifests as a change in metal balance in the brain and other organs and substantial oxidative damage throughout the brain. Thus prions and metals have become tightly linked in the quest to understand the nature of transmissible spongiform encephalopathies.

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