Design of novel JNK1 inhibitors using molecular modeling technique: An in silico approach
By: Nagpal, Ashima
.
Contributor(s): Paliwal, Sarvesh.
Publisher: New Delhi CSIR 2019Edition: Vol.58(B), March.Description: 403-415p.Subject(s): GENERAL CHEMISTRYOnline resources: Click here
In:
Indian journal of chemistry (Section B)Summary: To address the issue of unavailability of selective JNK1 inhibitors resulting in off-target effects, leading to multiple diseases, an endeavour to discover novel and specific JNK1 inhibitors is taken up in the present study. To achieve this goal, computer-aided drug design approach has been used and a validated 2D QSAR model, of excellent statistical quality, has been developed through MLR (Multiple Linear Regression) and PLS (Partial Lest Square) method. The r2 value obtained through PLS method (0.97) corroborated the r2 value that has been obtained through MLR approach (0.97). The insights obtained through in-depth study of the developed model has capacitated us to design optimized molecules (compound A1OOP and compound A2SSR) with better selectivity profile than the most active compound of the selected set of compounds that have been employed to build the QSAR model. Additionally, molecular docking and structure based pharmacophore design have been performed to ensure that the affinity of the designed molecules towards JNK1 receptor and evaluation of their ADME properties have been done to ensure their lead likeness. Further, extremely small values for Tanimoto similarity index are obtained that clearly suggest that the designed molecules are novel.
| Item type | Current location | Call number | Status | Date due | Barcode | Item holds |
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Articles Abstract Database
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School of Pharmacy Archieval Section | Not for loan | 2022-0315 |
To address the issue of unavailability of selective JNK1 inhibitors resulting in off-target effects, leading to multiple diseases, an endeavour to discover novel and specific JNK1 inhibitors is taken up in the present study. To achieve this goal, computer-aided drug design approach has been used and a validated 2D QSAR model, of excellent statistical quality, has been developed through MLR (Multiple Linear Regression) and PLS (Partial Lest Square) method. The r2 value obtained through PLS method (0.97) corroborated the r2 value that has been obtained through MLR approach (0.97). The insights obtained through in-depth study of the developed model has capacitated us to design optimized molecules (compound A1OOP and compound A2SSR) with better selectivity profile than the most active compound of the selected set of compounds that have been employed to build the QSAR model. Additionally, molecular docking and structure based pharmacophore design have been performed to ensure that the affinity of the designed molecules towards JNK1 receptor and evaluation of their ADME properties have been done to ensure their lead likeness. Further, extremely small values for Tanimoto similarity index are obtained that clearly suggest that the designed molecules are novel.
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