PF-04995274 is an orally active, brain-penetrant partial agonist of the serotonin 5-HT4 receptor. Initially investigated as a potential procognitive agent, it is identified by CAS 1331782-27-4 and is also known as TBPT.
Its scaffold contains a benzo[d]isoxazole connected to a substituted piperidine, a tetrahydrofuran ether, and a hydroxylated tetrahydropyran group. The formula is C23H32N2O6. The stereochemically defined parent compound should be distinguished from metabolites when interpreting pharmacological or exposure data.
Application of PF-04995274
The compound has been used to study how 5-HT4 receptor activation affects cAMP signaling, cholinergic neurotransmission, learning, and emotional processing. Researchers can apply it in recombinant receptor assays, brain-tissue experiments, and scopolamine-challenge models. Its partial agonist profile supports comparisons with full 5-HT4 agonists, while animal and human data help connect receptor-level findings with functional endpoints. It is a research compound, not an established therapy.
In Vitro
Published pharmacology for Pfizer PF-04995274 reports Ki values of 0.15–0.46 nM across the human 5-HT4A, 5-HT4B, 5-HT4D, and 5-HT4E variants. Functional cAMP assays give EC50 values of 0.26–0.47 nM. At the tested rat variants, reported EC50 values range from 0.59 to 0.65 nM.
These results describe the parent PF-04995274 structure in recombinant assay systems. The affinity and functional potency values should not be interpreted as direct measures of cognitive or antidepressant efficacy.
In Vivo
In rats, oral administration reduced the scopolamine-induced increase in distance travelled in the Morris water maze at 0.032 mg/kg. The compound was also reported to increase brain acetylcholine levels.
A human experimental-medicine study administered 15 mg once daily for 7 days to assess emotional processing and neural responses in participants with major depressive disorder. These short studies evaluated mechanistic endpoints, not confirmed clinical benefit. Metabolism should be considered when interpreting human exposure, because circulating drug-related material may include metabolites in addition to the parent compound.
Biochemical and Physiological Actions
The PF-04995274 chemical structure acts at the 5-HT4 receptor, a Gs-coupled GPCR. Receptor activation stimulates adenylyl cyclase, increases intracellular cAMP, and engages downstream signaling that can facilitate acetylcholine release in brain regions involved in learning and memory. Partial agonism describes a lower maximal response than that produced by a reference full agonist under the same assay conditions; it does not mean incomplete receptor binding.
Features and Benefits of PF-04995274
- Subnanomolar affinity and functional potency across tested human 5-HT4 receptor variants.
- Partial agonist pharmacology suitable for receptor-efficacy comparisons.
- Brain penetration and oral activity supporting translational study designs.
- Verified formula C23H32N2O6 and PF-04995274 molecular weight of 432.51 g/mol.
- Preclinical and human experimental data covering cognitive and emotional-processing endpoints.
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