Apremilast is a small molecule inhibitor of PDE4 with an IC50 value of 74 nM.
Apremilast/阿普司特 细胞实验
Cell Line
Concentration
Treated Time
Description
References
natural killer (NK) cells
10 μM
48 h
Inhibited NK cell production of TNF-α and GM-CSF
Br J Pharmacol. 2010 Feb;159(4):842-55.
polymorphonuclear cells (PMN)
94 nM (IC50)
18 h
Inhibited PMN production of IL-8
Br J Pharmacol. 2010 Feb;159(4):842-55.
Xenopus laevis oocytes
1–10 μM
Apremilast did not directly alter GABA A receptor function
Neuropharmacology. 2020 Nov 1;178:108220.
Draining lymph node cells
200 nM
72 h
To evaluate the effect of apremilast on balancing Treg and Teff cells. Results showed that apremilast significantly suppressed Th17 and Th1 cells and enhanced the proportion and population of Treg cells.
Front Immunol. 2020 Nov 17;11:581673.
CD4+CD25+ regulatory T cells
0.1 µM
24 h
To evaluate Apremilast's effect on Treg stability and conversion to Th17 cells. Results showed Apremilast pretreatment significantly increased Foxp3 expression, decreased IL-17a and CD126 expression, and maintained Treg suppressive function.
Apremilast reduced the expression and secretion of IL-1β and MCP-1 induced by IL-17 in a dose-dependent manner.
Int J Mol Med. 2021 Mar;47(3):12.
human neonatal foreskin epidermal keratinocytes (HEKn cells)
1 μM
18 h
Inhibited UVB light-activated keratinocyte production of TNF-α
Br J Pharmacol. 2010 Feb;159(4):842-55.
peripheral blood mononuclear cells (PBMC)
10 μM
18 h
Inhibited PBMC production of the chemokines CXCL9 and CXCL10, cytokines interferon-γ and tumour necrosis factor (TNF)-α, and interleukins (IL)-2, IL-12 and IL-23
Br J Pharmacol. 2010 Feb;159(4):842-55.
Raw264.7 monocytic murine cell line
104 nM (IC50)
30 min
Apremilast increased intracellular cAMP and inhibited TNF-α release with an IC50 of 104 nM.
Arthritis Res Ther. 2015 Sep 15;17(1):249.
Apremilast/阿普司特 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6J mice
BLM-induced systemic sclerosis (SSc) model
Oral
25 mg/kg and 5 mg/kg
Once daily for 4 consecutive weeks
Apremilast significantly ameliorated the pathological manifestations of SSc, including skin dermal thickness, deposition of collagens, and increased expression of α-SMA
Acta Pharmacol Sin. 2022 Feb;43(2):376-386
C57BL/6J mice
Experimental autoimmune uveitis (EAU) model
Oral gavage
15 mg/kg
Once daily for 14 days (from day 7 to day 21 after immunization)
To evaluate the therapeutic effect of apremilast on EAU. Results showed that apremilast significantly reduced vascular leakage, macular edema, and inflammatory cell infiltration in the retina, corresponding to decreased clinical and pathological scores. Additionally, apremilast decreased the proportion and population of Th17 cells and increased the proportion and population of Treg cells.
Front Immunol. 2020 Nov 17;11:581673.
DBA/1J mice
Collagen-induced arthritis (CIA) model
Oral
5 mg/kg or 25 mg/kg
Once daily for 10 consecutive days
To assess therapeutic effects of Apremilast in CIA. Results demonstrated delayed arthritis onset, reduced clinical scores, decreased anti-CII antibodies, prevented bone erosion, and modulated Th1/Th17/Treg balance (decreased Th17/Th1, increased Treg). High dose (25 mg/kg) showed superior efficacy.
Front Immunol. 2018 Jul 18;9:1662.
Beige-severe combined immunodeficient mice
Mouse model xenotransplanted with normal human skin and triggered with human psoriatic NK cells
Oral
5 mg/kg
Twice daily for 14 days
Significantly reduced epidermal thickness and proliferation, decreased the general histopathological appearance of psoriasiform features and reduced expression of TNF-α, human leukocyte antigen-DR and intercellular adhesion molecule-1 in the lesioned skin
Br J Pharmacol. 2010 Feb;159(4):842-55.
C57BL/6J mice
Models of ethanol- and other GABAergic drug-induced sedative-hypnotic effects and ataxia
Oral
20 mg/kg
Once daily for 1 hour
Apremilast prolonged the sedative-hypnotic effects of ethanol, gaboxadol, zolpidem, and propofol and prolonged recovery from ataxia induced by ethanol, zolpidem, propofol, and loreclezole, but shortened the sedative-hypnotic and ataxic effects of diazepam. The PKA inhibitor H89 blocked these modulatory effects of apremilast.
Neuropharmacology. 2020 Nov 1;178:108220.
Mice
Β3-S408A/S409A knock-in mice
Oral
20 mg/kg
Once daily for 1 hour
Apremilast increases acute sensitivity to alcohol, decreases AFT, and decreases ethanol drinking through PKA-dependent phosphorylation of β3 GABA A receptor subunits
Neuropharmacology. 2022 Dec 1;220:109255
Mice
Murine air pouch model
Oral
5 mg/kg
24 hours and 1 hour before inflammation induction
Apremilast significantly inhibited TNF-α production in the air pouch by 39% and reduced leukocyte count by 28%.
搜索
