scholarly journals A computer‐driven scaffold‐hopping approach generating new PTP1B inhibitors from the pyrrolo[1,2‐a]quinoxaline core

ChemMedChem ◽  
2021 ◽  
Author(s):  
Javier García-Marín ◽  
Mercedes Griera ◽  
Ramón Alajarín ◽  
Manuel Rodríguez-Puyol ◽  
Diego Rodríguez-Puyol ◽  
...  
Keyword(s):  
Scaffold Hopping ◽  
Ptp1b Inhibitors

Discovery of novel PTP1B inhibitors via pharmacophore-oriented scaffold hopping from Ertiprotafib

2013 ◽  
Vol 23 (23) ◽  
pp. 6217-6222 ◽  
Author(s):  
Jun-Zheng Liu ◽  
Shu-En Zhang ◽  
Feilin Nie ◽  
Ying Yang ◽  
Yan-Bo Tang ◽  
...  
Keyword(s):  
Scaffold Hopping ◽  
Ptp1b Inhibitors

Identification of novel PTP1B inhibitors by pharmacophore based virtual screening, scaffold hopping and docking

2014 ◽  
Vol 87 ◽  
pp. 578-594 ◽  
Author(s):  
Vishal M. Balaramnavar ◽  
Rohit Srivastava ◽  
Neha Rahuja ◽  
Swati Gupta ◽  
Arun K. Rawat ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Scaffold Hopping ◽  
Ptp1b Inhibitors

AutoLinker: Automatic Fragment Linking with Deep Conditional Transformer Neural Networks

2020 ◽  
Author(s):  
Yuyao Yang ◽  
Shuangjia Zheng ◽  
Shimin Su ◽  
Jun Xu ◽  
Hongming Chen
Keyword(s):  
Neural Networks ◽  
Drug Discovery ◽  
Drug Design ◽  
State Of The Art ◽  
The State ◽  
Generative Model ◽  
Lead Optimization ◽  
Scaffold Hopping ◽  
Reference Models ◽  
Lead Generation

Fragment based drug design represents a promising drug discovery paradigm complimentary to the traditional HTS based lead generation strategy. How to link fragment structures to increase compound affinity is remaining a challenge task in this paradigm. Hereby a novel deep generative model (AutoLinker) for linking fragments is developed with the potential for applying in the fragment-based lead generation scenario. The state-of-the-art transformer architecture was employed to learn the linker grammar and generate novel linker. Our results show that, given starting fragments and user customized linker constraints, our AutoLinker model can design abundant drug-like molecules fulfilling these constraints and its performance was superior to other reference models. Moreover, several examples were showcased that AutoLinker can be useful tools for carrying out drug design tasks such as fragment linking, lead optimization and scaffold hopping.

Potential Inhibitors of Protein Tyrosine Phosphatase (PTP1B) Enzyme: Promising Target for Type-II Diabetes Mellitus

2020 ◽  
Vol 20 (29) ◽  
pp. 2692-2707
Author(s):  
Sisir Nandi ◽  
Mridula Saxena
Keyword(s):  
Insulin Receptor ◽  
Protein Tyrosine Phosphatase ◽  
Type Ii Diabetes ◽  
Tyrosine Phosphatase ◽  
Type Ii Diabetes Mellitus ◽  
Type Ii ◽  
Insulin Effect ◽  
Protein Tyrosine ◽  
Ptp1b Inhibitors ◽  
Insulin Dependent Diabetic

Background: There has been growing interest in the development of highly potent and selective protein tyrosine phosphatase (PTP1B) inhibitors for the past 2-3 decades. Though most PTPs share a common active site motif, the interest in selective inhibitors, particularly against PTP1B is increasing to discover new chemical entities as antidiabetic agents. In the current paradigm to find potent and selective PTP1B inhibitors, which is currently considered as one of the best validated biological targets for non-insulin-dependent diabetic and obese individuals, resistance to insulin due to decreased sensitivity of the insulin receptor is a pathological factor and is also genetically linked, causing type II diabetes. Objectives: Insulin receptor sensitization is performed by a signal transduction mechanism via a selective protein tyrosine phosphatase (PTP1B). After the interaction of insulin with its receptor, autophosphorylation of the intracellular part of the receptor takes place, turning it into an active kinase (sensitization). PTP1B is involved in the desensitization of the receptor by dephosphorylation. PTP1b inhibitors delay the receptor desensitization, prolonging insulin effect and making PTP1B as a drug target for the treatment of diabetes II. Therefore, it has become a major target for the discovery of potent drugs for the treatment of type II diabetes and obesity. An attempt has been made in the present study to discuss the latest design and discovery of protein tyrosine phosphatase (PTP1B) inhibitors. Methods: Many PTP1B inhibitors such as diaminopyrroloquinazoline, triazines, pyrimido triazine derivatives, 2-(benzylamino)-1-phenylethanol, urea, acetamides and piperazinylpropanols, phenylsulphonamides and phenylcarboxamide, benzamido, arylcarboxylic acid derivatives, arylsupfonyl derivatives, thiazoles, isothiozolidiones and thiazolodinones have been discussed, citing the disease mechanisms. Results: The reader will gain an overview of the structure and biological activity of recently developed PTPs inhibitors. Conclusion: The co-crystallized ligands and the screened inhibitors could be used as a template for the further design of potent congeners.

QSAR Studies of PTP1B Inhibitors: 1, 2-Naphthoquinone Derivatives

2012 ◽  
Vol 9 (10) ◽  
pp. 915-925
Author(s):  
Feng Luan ◽  
Xuan Xu ◽  
Huitao Liu ◽  
Maria Natalia Dias Soeiro Cordeiro ◽  
Xiaoyun Zhang
Keyword(s):  
Qsar Studies ◽  
Ptp1b Inhibitors

Drug repurposing using similarity-based target prediction, docking studies and scaffold hopping of lefamulin

2020 ◽  
Vol 17 ◽  
Author(s):  
Shikha Sharma ◽  
Shweta Sharma ◽  
Vaishali Pathak ◽  
Parwinder Kaur ◽  
Rajesh Kumar Singh
Keyword(s):  
In Silico ◽  
Target Prediction ◽  
Drug Repurposing ◽  
Docking Studies ◽  
Target Protein ◽  
Future Perspective ◽  
Antibacterial Drug ◽  
Scaffold Hopping ◽  
Target Proteins ◽  
Renin Inhibitors

Aim: To investigate and validate the potential target proteins for drug repurposing of newly FDA approved antibacterial drug. Background: Drug repurposing is the process of assigning indications for drugs other than the one(s) that they were initially developed for. Discovery of entirely new indications from already approved drugs is highly lucrative as it minimizes the pipeline of the drug development process by reducing time and cost. In silico driven technologies made it possible to analyze molecules for different target proteins which are not yet explored. Objective: To analyze possible targets proteins for drug repurposing of lefamulin and their validation. Also, in silico prediction of novel scaffolds from lefamulin has been performed for assisting medicinal chemists in future drug design. Methods: A similarity-based prediction tool was employed for predicting target protein and further investigated using docking studies on PDB ID: 2V16. Besides, various in silico tools were employed for prediction of novel scaffolds from lefamulin using scaffold hopping technique followed by evaluation with various in silico parameters viz., ADME, synthetic accessibility and PAINS. Results: Based on the similarity and target prediction studies, renin is found as the most probable target protein for lefamulin. Further, validation studies using docking of lefamulin revealed the significant interactions of lefamulin with the binding pocket of the target protein. Also, three novel scaffolds were predicted using scaffold hopping technique and found to be in the limit to reduce the chances of drug failure in the physiological system during the last stage approval process. Conclusion: To encapsulate the future perspective, lefamulin may assist in the development of the renin inhibitors and, also three possible novel scaffolds with good pharmacokinetic profile can be developed into both as renin inhibitors and for bacterial infections.

Peptidomimetics as Potent and Selective PTP1B Inhibitors

2013 ◽  
Vol 9 (5) ◽  
pp. 660-671
Author(s):  
Dipam Patel ◽  
Mukul Jain ◽  
Shailesh Shah ◽  
Rajesh Bahekar ◽  
Pradip Jadav ◽  
...  
Keyword(s):  
Ptp1b Inhibitors

scholarly journals 2-Cyclopropyl-6-phenyl-2,3-dihydrothieno[3,2-d][1,3,2]diazaborinin-4(1H)-one

Molbank ◽  
10.3390/m1221 ◽  
2021 ◽  
Vol 2021 (2) ◽  
pp. M1221
Author(s):  
Romain Mustière ◽  
Patrice Vanelle ◽  
Nicolas Primas
Keyword(s):  
Scaffold Hopping ◽  
Simple Treatment ◽  
Biological Tests

As part of our ongoing scaffold hopping work on antimalarial 2-aminothieno[3,2-d]pyrimidin-4-one scaffold, we explored the dihydrothieno[3,2-d][1,3,2]diazaborinin-4(1H)-one as a potential new antimalarial series. Using conditions found in the literature, we obtained 2-cyclopropyl-6-phenyl-2,3-dihydrothieno[3,2-d][1,3,2]diazaborinin-4(1H)-one with 93% yield through a simple treatment. It was then characterized by NMR (1H and 13C) and HRMS. Given the structure of this molecule, its aqueous stability was assessed to determine its suitability for biological tests. To our knowledge, this is the first dihydrothieno[3,2-d][1,3,2]diazaborinin-4(1H)-one described.

scholarly journals From quinoline to quinazoline‐based S. aureus NorA efflux pump inhibitors by coupling focused scaffold hopping approach and pharmacophore search

ChemMedChem ◽  
2021 ◽  
Author(s):  
Nicholas Cedraro ◽  
Rolando Cannalire ◽  
Andrea Astolfi ◽  
Gianmarco Mangiaterra ◽  
Tommaso Felicetti ◽  
...  
Keyword(s):  
Efflux Pump ◽  
Scaffold Hopping ◽  
Efflux Pump Inhibitors
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