PF-05231023 (Synonyms: Mal-PEG2-AZD)

PF-05231023, a long-acting fibroblast growth factor 21 (FGF21) analog, is a FGF21-receptor agonist, suitable for development as a potential treatment for T2DM[1][5].

PF-05231023 is a long-acting fibroblast growth factor 21 (FGF21) analog[2].

Administration of native FGF21 and PF-05231023 ( 3 mg/kg or 10 mg/kg ) improves glucose tolerance and liver insulin sensitivity in Zucker rats[3].PF-05231023 (10 mg/kg) shows protective effects on Akita retinas. PF-05231023 (10 mg/kg) decreases retinal inflammation in diabetic mice. PF-05231023 (10 mg/kg) administration reduces retinal IL-1β mRNA expression in Akita mice. PF-05231023 (10 mg/kg) administration increases cone-specific arrestin4 expression in Akita mice. PF-05231023 (10 mg/kg) administration restores photoreceptor morphology in Akita mice. PF-05231023 (10 mg/kg) inhibits oxidative-stress-induced inflammation in photoreceptors. PF-05231023 (10 mg/kg) administration decreases the variability of retinal NRF2 levels and shows a trend (non-significant) towards increased NRF2 levels in Akita mice[4].

References:
[1]. Dong JQ, et al. Pharmacokinetics and pharmacodynamics of PF-05231023, a novel long-acting FGF21 mimetic, in a first-in-human study. Br J Clin Pharmacol. 2015 Nov;80(5):1051-63.
[2]. Giragossian C, et al. Mechanistic investigation of the preclinical pharmacokinetics and interspecies scaling of PF-05231023, a fibroblast growth factor 21-antibody protein conjugate. Drug Metab Dispos. 2015 Jun;43(6):803-11.
[3]. Bernardo B, et al. FGF21 does not require interscapular brown adipose tissue and improves liver metabolic profile in animal models of obesity and insulin-resistance. Sci Rep. 2015 Jul 8;5:11382.
[4]. Fu Z, et al. Fibroblast Growth Factor 21 Protects Photoreceptor Function in Type 1 Diabetic Mice. Diabetes. 2018 May;67(5):974-985.
[5]. Sonoda J, et al. FGF21-receptor agonists: an emerging therapeutic class for obesity-related diseases. Horm Mol Biol Clin Investig. 2017 May 19;30(2).