Pharmacophore-driven design and biological evaluation of heterocyclic PDE4B inhibitors for Alzheimer's disease
Karthik G. Pujar, Dipen Purohit, Richa Prabhakar Shetty, Parthasarathi S, Krishna Yallappa Kolachi, Aishwarya Bharathi H. M., Pooja Gandharvachari Achar, Prabitha P. · 2026
Read Pharmacophore-driven design and biological evaluation of heterocyclic PDE4B inhibitors for Alzheimer's disease by Karthik G. Pujar, Dipen Purohit, Richa Prabhakar Shetty, Parthasarathi S, Krishna Yallappa Kolachi, Aishwarya Bharathi H. M., Pooja Gandharvachari Achar, Prabitha P. (2026) in the Tower of Babel, a free online library of public-domain works preserved in clean, searchable text. No sign-up. The full text is served as a plain-text file at a predictable URL, where text is present: https://antarctic-labs.com/tower-of-babel/PMC13394277.txt.
Description
Karthik G Pujar and seven colleagues designed new drug candidates against PDE4B, an enzyme that drains the messenger molecule cAMP inside brain and immune cells, as a route into Alzheimer's disease. Raising cAMP could calm brain inflammation and support synaptic signalling, but older PDE4 drugs are dose-limited by side effects, so selectivity for the B form matters. Starting from two known modulators, the team extracted the shared pharmacophore features and built six ring-based derivatives tuned for brain entry and pocket fit without leaning on metal binding.
Two pyridine-based candidates stood out for brain compatibility and stable binding in simulations. The series was checked in nerve-like PC12 cells for protection and in fruit flies as a living Alzheimer's model. The authors present the pyridine heterocycles as credible starting points for PDE4B-targeted Alzheimer's therapy, with optimisation still ahead.
Catalog record
| CREATOR | Karthik G. Pujar, Dipen Purohit, Richa Prabhakar Shetty, Parthasarathi S, Krishna Yallappa Kolachi, Aishwarya Bharathi H. M., Pooja Gandharvachari Achar, Prabitha P. |
|---|---|
| YEAR | 2026 |
| COLLECTION | PAPERS |
| FORMAT | TXT |
| FILE SIZE | 54103 |
| LICENSE | https://creativecommons.org/licenses/by/4.0 |
| RIGHTS | CC BY |
| SOURCE | Europe PMC |