Naloxegol (oxalate)

Naloxegol is a peripherally acting antagonist of the µ-opioid receptor (Ki = 7.42 nM, pA2 = 7.95). It is selective for the µ-opioid receptor over the delta-opioid receptor (Ki = 866 nM). Naloxegol also acts as a partial agonist of kappa-opioid receptors in vitro (EC50 = 47 nM for [35S]GTPgammaS binding) but lacks activity ex vivo at concentrations up to 10 µM. In vivo, naloxegol reverses morphine-induced decreases in gastrointestinal motility and analgesia in a hot-plate assay in rats (ED50s = 23.1 and 55.4 mg/kg, respectively), demonstrating a two-fold separation for peripheral versus CNS effects. Naloxegol also exhibits a brain uptake rate comparable to atenolol, a low-permeation standard with no brain uptake, in a rat brain perfusion model.Formal Name: (5alpha,6alpha)-4,5-epoxy-6-(3,6,9,12,15,18,21-heptaoxadocos-1-yloxy)-17-(2-propen-1-yl)-morphinan-3,14-diol, monoethanedioate. CAS Number: 1354744-91-4. Synonyms: AZ 13337019, NKTR-118. Molecular Formula: C34H53NO11 . C2H2O4. Formula Weight: 741.8. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 16 mg/ml, DMSO: 20 mg/ml, Ethanol: 33 mg/ml, PBS (pH 7.2): 10 mg/ml. lambdamax: 212 nm. SMILES: O[C@]12[C@]3(CCN(CC=C)[C@@H]2C4)[C@](OC5=C3C4=CC=C5O)([H])[C@@H](OCCOCCOCCOCCOCCOCCOCCOC)CC1.OC(C(O)=O)=O. InChi Code: InChI=1S/C34H53NO11.C2H2O4/c1-3-9-35-10-8-33-30-26-4-5-27(36)31(30)46-32(33)28(6-7-34(33,37)29(35)25-26)45-24-23-44-22-21-43-20-19-42-18-17-41-16-15-40-14-13-39-12-11-38-2,3-1(4)2(5)6/h3-5,28-29,32,36-37H,1,6-25H2,2H3,(H,3,4)(H,5,6)/t28-,29+,32-,33-,34+,/m0./s1. InChi Key: MNYIRXLCPODKLG-VUTNLTPYSA-N.