Skip to main content
padlock icon - secure page this page is secure

CYP2J2 is the major enzyme in human liver microsomes responsible for hydroxylation of SYL‐927, a novel and selective sphingosine 1‐phosphate receptor 1 (S1P1) agonist

Buy Article:

$52.00 + tax (Refund Policy)

SYL‐927, a novel and selective S1P1 agonist, is transferred to its active phosphate for the regulation of lymphocyte recirculation. This in vitro metabolism study is to elucidate the P450‐mediated oxidation pathway of SYL‐927 in human liver microsomes (HLMs). The results demonstrated that the ω‐1 hydroxylated metabolite SYL‐927‐M was formed after incubation of SYL‐927 with HLMs. Recombinant human CYP1A1 and CYP2J2 can efficiently catalyse SYL‐927‐M formation, followed by markedly less substrate conversion with CYP1A2, CYP2C19 and CYP2D6. Inhibition studies with chemical inhibitors and antibodies suggested that arachidonic acid, the substrate of CYP2J2, and CYP2J2‐specific antibody effectively inhibited the formation of SYL‐927‐M in HLMs whereas no significant inhibition was observed with the inhibitors for CYP1A1, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1 and CYP3A4, demonstrating that CYP2J2 was primarily responsible for the formation of SYL‐927‐M.
No References
No Citations
No Supplementary Data
No Article Media
No Metrics

Keywords: CYP2J2; S1P1 agonist; human liver microsomes; ω‐1 hydroxylation

Document Type: Research Article

Publication date: November 1, 2018

  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
X
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more