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PF-07258669 (pf-07258669)
PF-07258669 is a selective MC4R antagonist that blocks melanocortin-4 receptor signaling to increase appetite and food intake.
PF-07258669 is a selective melanocortin-4 receptor (MC4R) antagonist developed by Pfizer for the potential treatment of appetite loss and cachexia. The compound was designed to block MC4R signaling in the hypothalamus, thereby increasing appetite and food intake through modulation of pro-opiomelanocortin (POMC) neurons. The program progressed through Phase 1 clinical trials in healthy volunteers and older adults, demonstrating pharmacokinetic characterization and tolerability; however, Pfizer discontinued development, and the drug did not advance to Phase 2 or receive regulatory approval. The discontinuation reflects either safety or efficacy concerns identified during early-stage evaluation, or a strategic portfolio decision. No approved indications exist, and the compound remains a research-stage asset with limited commercial significance.
At a glance
| Generic name | pf-07258669 |
|---|---|
| Sponsor | Pfizer Inc. |
| Drug class | MC4R antagonist |
| Target | Melanocortin-4 receptor (MC4R) |
| Modality | Small molecule |
| Therapeutic area | Oncology |
| Phase | discontinued |
Mechanism of action
PF-07258669 works by antagonizing the melanocortin-4 receptor (MC4R), a G-protein coupled receptor located in the hypothalamus that plays a central role in appetite regulation. MC4R is part of the melanocortin system, which includes pro-opiomelanocortin (POMC) neurons that suppress appetite when activated. By blocking MC4R, PF-07258669 inhibits the appetite-suppressing signal, thereby promoting hunger and increasing food intake. This mechanism is particularly relevant for patients with appetite loss, cachexia, or wasting syndromes associated with chronic diseases, aging, or cancer. The selectivity of PF-07258669 for MC4R over other melanocortin receptors (MC1R, MC3R, MC5R) is intended to minimize off-target effects and improve tolerability.
Approved indications
Pipeline indications
- Appetite loss / Cachexia — Phase 1
Common side effects
Drug interactions
- Itraconazole
Key clinical trials
- A Study to Learn About the Study Medicine Called PF-07258669 in Older Adults Including Those at Risk of Malnutrition (PHASE1)
- A Study to Learn if the Study Medicine Called Itraconazole and if Food Changes How the Body Processes the Other Study Medicine Called PF 07258669 in Older Adults or Healthy Adults (PHASE1)
- A Study of PF-07258669 In Healthy Adult Participants (PHASE1)
- A Study of Single Ascending Doses of PF-07258669 in Healthy Adult Participants (PHASE1)
Primary sources
Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.
| Source | Used for |
|---|---|
| ClinicalTrials.gov | Trial enrolment, design, endpoints, results |
Competitive intelligence
For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:
- PF-07258669 CI brief — competitive landscape report
- PF-07258669 updates RSS · CI watch RSS
- Pfizer Inc. portfolio CI