PF-00489791

SKU: orb1699668

Description

PF-00489791 (PF4634817) is a long-acting phosphodiesterase 5 (PDE5) inhibitor investigated for its potential to lower blood pressure and mitigate renal injury. Its application is primarily in preclinical research for diabetic nephropathy, utilizing both in vitro enzymatic assays and in vivo animal models of diabetes to study renal protection.

Research Area

Metabolism Research

Key Properties

• CAS Number: 853003-48-2
• MW: 476.55
• Purity: >99.99% (May vary between batches)
• Formula: C₂₀H₂₈N₈O₄S
• SMILES: C(NS(C)(=O)=O)(=O)C=1C=2C(=C(NC3=CC(C)=CC=N3)N=C(N(CC)C)N2)N(CCOCC)N1
• Target: PDE

Bioactivity

• Target IC50:
  PDE5A:5 nM
• In Vivo:
  The novel, highly specific, and long-acting PDE5 inhibitor, PF-00489791, was assessed in a multinational, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial of subjects with type 2 diabetes mellitus and overt nephropathy receiving angiotensin-converting enzyme inhibitor or angiotensin receptor blocker background therapy. In total, 256 subjects with an eGFR between 25 and 60 ml/min per 1.73 m2 and macroalbuminuria defined by a urinary albumin-to-creatinine ratio >300 mg/g, were randomly assigned 3:1, respectively, to receive PF-00489791 (20 mg) or placebo orally, once daily for 12 weeks. Using the predefined primary assessment of efficacy (Bayesian analysis with informative prior), we observed a significant reduction in the urinary albumin-to-creatinine ratio of 15.7% (ratio 0.843; 95% credible interval 0.73 to 0.98) in response to the 12-week treatment with PF-00489791 compared with placebo. PF-00489791 was safe and generally well tolerated in this patient population. Most common adverse events were mild in severity and included headache and upper gastrointestinal events. In conclusion, the safety and efficacy profile of PDE5 inhibitor PF-00489791 supports further investigation as a novel therapy to improve renal outcomes in DN.
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

PF 00489791, PF4634817, PF-4634817, PF 4634817, PF00489791, PF-00489791, PDE5

Compound Identifiers

PubChem CID

11465695