Small Molecule · MK-1167
MK-1167
Oral, selective Type I positive allosteric modulator (PAM) of the alpha-7 nicotinic acetylcholine receptor (alpha7 nAChR / CHRNA7) in Phase 2 development by Merck (MSD) for cognition in mild-to-moderate Alzheimer's disease dementia. Derived from the Bionomics alpha-7 nAChR PAM program (lead preclinical molecule BNC375; Bionomics is now Neuphoria Therapeutics) licensed to Merck in 2014. As a Type I PAM it amplifies the peak acetylcholine-evoked alpha7 current with little effect on receptor desensitization kinetics, a profile hypothesized to improve cognition while avoiding the rapid desensitization seen with alpha7 agonists.
Also known as: MK-1167, BNC375, 1557240-80-8
- Modality
- Small molecule
- Chemical class
- cyclopropane, aniline, benzenesulfonamide
- Chemistry
- Single enantiomer
- Mechanism
- alpha7 nAChR PAM
- Highest phase
- Phase 2
- Lead indication
- Alzheimer's disease
- Developer
- Merck & Co., Inc. (MRK)
- Trials
- 1 tracked · 72 sites
- Next catalyst
- 2H 2026 — Topline data (Alzheimer's disease)
Mechanism of action
MK-1167 is a selective Type I positive allosteric modulator of the alpha-7 nicotinic acetylcholine receptor (alpha7 nAChR, encoded by CHRNA7). It binds an allosteric site and potentiates the peak current evoked by endogenous acetylcholine without substantially altering the receptor's rapid desensitization kinetics (Type I PAM behavior), enhancing cholinergic / alpha7 nicotinic signaling implicated in cognition. The named program lead BNC375 has a reported functional potentiation EC50 of ~1.3 uM at the human alpha7 nAChR.
| Target | Action | Affinity |
|---|---|---|
| alpha7 nAChRprimaryCHRNA7 | PAM | EC50 1.3 uMⓘ |
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| MK-1167 oral capsule Oral capsule; 0.3 mg, 1 mg, or 3 mg once daily in Phase 2 (MK-1167-008) | Oral | Once daily | — |
Development timeline
- UpcomingPhase 2 topline efficacy/safety of MK-1167 (vs placebo) on cognition in mild-to-moderate Alzheimer's disease dementia (MK-1167-008)
- Phase 1 healthy-volunteer biomarker data: single doses of MK-1167 modulate prefrontal-cortex glutamate metabolism measured by 13C-magnetic resonance spectroscopy (presented at CTAD 2025)↗
- Phase 2 study NCT06721156 (MK-1167-008) of MK-1167 as adjunctive therapy in mild-to-moderate Alzheimer's disease dementia first posted/started; this Phase 2 initiation triggered a USD 15M milestone payment from Merck to Neuphoria Therapeutics (formerly Bionomics), the program's originator, announced 2025-02-12.↗
MK-1167 for Alzheimer's disease
Phase 2ActiveAlzheimer's disease indication →
Phase 2 program evaluating MK-1167 as adjunctive therapy (on stable acetylcholinesterase inhibitor / donepezil background) for cognition in participants with mild-to-moderate Alzheimer's disease dementia. The pivotal/lead Phase 2 study is NCT06721156 (MK-1167-008). Phase 1 prefrontal glutamate metabolism (13C-MRS) biomarker data in healthy volunteers were presented at CTAD 2025. No FDA expedited-program designation publicly reported for MK-1167.
Readouts
- 2H 2026AnticipatedTopline dataNCT06721156
Phase 2 topline efficacy/safety of MK-1167 (vs placebo) on cognition in mild-to-moderate Alzheimer's disease dementia (MK-1167-008)
- 2025-12-01ReportedInterim analysis
Phase 1 healthy-volunteer biomarker data: single doses of MK-1167 modulate prefrontal-cortex glutamate metabolism measured by 13C-magnetic resonance spectroscopy (presented at CTAD 2025) ↗
Clinical trials
NCT06721156MK-1167-008Phase 2Activen=350
A Phase 2 Randomized, Placebo-Controlled, Double-Blind, Parallel-group Study to Evaluate the Efficacy and Safety of MK-1167 as Adjunctive Therapy in Participants With Mild to Moderate Alzheimer's Disease Dementia
Identifiers
- ChEMBL CHEMBL4456125
- PubChem CID 118160666
Sources
- A Study to Evaluate the Efficacy and Safety of MK-1167 in Participants With Alzheimer's Disease Dementia (MK-1167-008) — ClinicalTrials.gov (U.S. National Library of Medicine)
- Discovery of BNC375, a Potent, Selective, and Orally Available Type I Positive Allosteric Modulator of alpha7 nAChRs — ACS Medicinal Chemistry Letters (PubMed)
- Merck Showcases Data for Alzheimer's Disease Candidates MK-2214 and MK-1167 at CTAD 2025 — Merck & Co., Inc.
- Neuphoria Therapeutics Inc. to Receive $15M Milestone Payment from Merck — Neuphoria Therapeutics Inc. (GlobeNewswire)