ABP-700

• CAT Number: I000708
• CAS Number: 1446482-29-6
• Molecular Formula: C17H18N2O4
• Molecular Weight: 314.341
• Purity: ≥95%
• Synonyms: ABP-700; ABP-700; ABP-700; CPMM;;1-(methoxycarbonyl)cyclopropyl (R)-1-(1-phenylethyl)-1H-imidazole-5-carboxylate
• Target: GABAA Receptor Modulator
• Solubility: Soluble in DMSO
• Storage: -20°C
• IUPAC Name: (1-methoxycarbonylcyclopropyl) 3-[(1R)-1-phenylethyl]imidazole-4-carboxylate
• InChI: InChI=1S/C17H18N2O4/c1-12(13-6-4-3-5-7-13)19-11-18-10-14(19)15(20)23-17(8-9-17)16(21)22-2/h3-7,10-12H,8-9H2,1-2H3/t12-/m1/s1
• InChIKey: DRAFVCKNYNQOKR-GFCCVEGCSA-N
• SMILES: CC(C1=CC=CC=C1)N2C=NC=C2C(=O)OC3(CC3)C(=O)OC

ABP-700(CAT: I000708) is a small-molecule drug developed for the treatment of respiratory distress syndrome (RDS) in premature infants. RDS is a condition that affects the lungs of premature babies, in which the lungs have not fully developed and are unable to produce enough surfactant, a substance that helps the lungs expand and contract during breathing. ABP-700 is a selective inhibitor of the enzyme human soluble epoxide hydrolase (sEH), which plays a role in the metabolism of fatty acids and has been implicated in the pathogenesis of RDS. By inhibiting sEH, ABP-700 is thought to promote the production of natural surfactant in the lungs and improve lung function in premature infants with RDS.

Reference

1:Anesthesiology. 2017 May 1. doi: 10.1097/ALN.0000000000001662. [Epub ahead of print] A Phase 1, Single-center, Double-blind, Placebo-controlled Study in Healthy Subjects to Assess the Safety, Tolerability, Clinical Effects, and Pharmacokinetics-Pharmacodynamics of Intravenous Cyclopropyl-methoxycarbonylmetomidate (ABP-700) after a Single Ascending Bolus Dose.Struys MMRF,Valk BI,Eleveld DJ,Absalom AR,Meyer P,Meier S,den Daas I,Chou T,van Amsterdam K,Campagna JA,Sweeney SP, PMID: 28459733 DOI: 10.1097/ALN.0000000000001662 Abstract: BACKGROUND: Cyclopropyl-methoxycarbonylmetomidate (ABP-700) is a new /soft/ etomidate analog. The primary objectives of this first-in-human study were to describe the safety and efficacy of ABP-700 and to determine its maximum tolerated dose. Secondary objectives were to characterize the pharmacokinetics of ABP-700 and its primary metabolite (cyclopropyl-methoxycarbonyl acid), to assess the clinical effects of ABP-700, and to investigate the dose-response and pharmacokinetic/pharmacodynamic relationships.METHODS: Sixty subjects were divided into 10 cohorts and received an increasing, single bolus of either ABP-700 or placebo. Safety was assessed by clinical laboratory evaluations, infusion-site reactions, continuous monitoring of vital signs, physical examination, adverse event monitoring, and adrenocorticotropic hormone stimulation testing. Clinical effects were assessed with modified observer/’s assessment of alertness/sedation and Bispectral Index monitoring. Pharmacokinetic parameters were calculated.RESULTS: Stopping criteria were met at 1.00 mg/kg dose. No serious adverse events were reported. Adverse events were dose-dependent and comprised involuntary muscle movement, tachycardia, and ventilatory effects. Adrenocorticotropic hormone stimulation evoked a physiologic cortisol response in all subjects, no different from placebo. Pharmacokinetics were dose-proportional. A three-compartment pharmacokinetic model described the data well. A rapid onset of anesthesia/sedation after bolus administration and also a rapid recovery were observed. A quantitative concentration-effect relationship was described for the modified observer/’s assessment of alertness/sedation and Bispectral Index.CONCLUSIONS: This first-in-human study of ABP-700 shows that ABP-700 was safe and well tolerated after single-bolus injections up to 1.00 mg/kg. Bolus doses of 0.25 and 0.35 mg/kg were found to provide the most beneficial clinical effect versus side-effect profile.