AM580 is a retinoic acid analog, working as a selective RARα agonist with EC50 values of 0.3, 8.6 and 13 nM for RARα, RARβ and RARγ respectively. AM580 at concentration of 100nM could recapitulate all of the T cell activation and type 2 cytokine-inducing effects of ATRA and 9-cis-RA on promotion of IL-4, IL-5 and IL-13 synthesis, while decreasing IFN-γ and TNF-α expression by activated human T cells and reduces the synthesis of IL-12p70 from accessory cells. Enhancing RA signaling by AM580 at concentration of 10nM profoundly promoted reprogramming of MEFs with transfected with four transcription factors (Oct4, Sox2, c-Myc, and Klf4), shown as substantial increase of the number of AP+ iPSC colonies.
AM580 细胞实验
Cell Line
Concentration
Treated Time
Description
References
A549 cells
20 µM
24 hours
AM580 significantly inhibited MERS-CoV replication in A549 cells
Nat Commun. 2019 Jan 10;10(1):120.
HEp-2 cells
20 µM
24 hours
AM580 significantly inhibited AdV5 replication in HEp-2 cells
Nat Commun. 2019 Jan 10;10(1):120.
RD cells
20 µM
24 hours
AM580 significantly inhibited EV-A71 replication in RD cells
Nat Commun. 2019 Jan 10;10(1):120.
Vero cells
20 µM
24 hours
AM580 significantly inhibited MERS-CoV replication in Vero cells
Nat Commun. 2019 Jan 10;10(1):120.
MDA-MB-231 cells
200 nM
48 hours
Increased RBP1 expression and atRA production
Cells. 2022 Feb 24;11(5):792.
MCF-7 cells
200 nM
48 hours
Increased RBP1 expression and atRA production
Cells. 2022 Feb 24;11(5):792.
HEK293T cells
100 µM
AM580 activated TRPV1-mediated calcium influx
J Clin Invest. 2013 Sep;123(9):3941-51.
Primary microglia
100 µM
12 hours
Am580 markedly attenuated TLR agonists-induced iNOS expression, without canceling their basic immune response.
J Neuroinflammation. 2022 Jan 6;19(1):5.
MMTV-wnt1 cells
50 nM
13 days
AM580 treatment increased caspase-3 expression in all of the colonies, and in 30% of the colonies induced acinar-like cavitation
Oncogene. 2010 Jun 24;29(25):3665-76.
THP-1 cells
20 µM
24 hours
AM580 significantly inhibited MERS-CoV replication in THP-1 cells
Nat Commun. 2019 Jan 10;10(1):120.
Calu-3 cells
20 µM
24 hours
AM580 significantly inhibited MERS-CoV replication in Calu-3 cells
Nat Commun. 2019 Jan 10;10(1):120.
Huh7 cells
20 µM
24 hours
AM580 significantly reduced MERS-CoV replication, viral titers decreased by >3-log10
Nat Commun. 2019 Jan 10;10(1):120.
ACE2-HeLa cells
20 µM
24 hours
AM580 significantly inhibited SARS-CoV-2 replication in ACE2-HeLa cells.
Proc Natl Acad Sci U S A. 2021 Sep 14;118(37):e2107108118.
Vero-E6 cells
20 µM
24 hours
AM580 significantly inhibited SARS-CoV-2 replication in Vero-E6 cells.
Proc Natl Acad Sci U S A. 2021 Sep 14;118(37):e2107108118.
Huh7 cells
20 µM
24 hours
AM580 treatment significantly inhibited SARS-CoV-2 replication, as demonstrated by a decrease in viral protein expression and viral RNA copies.
Proc Natl Acad Sci U S A. 2021 Sep 14;118(37):e2107108118.
MCF-7 cells
500 nM
24 hours
To evaluate the activation effect of AM580 on the RARβ promoter, results showed that AM580 significantly increased the activity of the RARβ promoter.
Cells. 2022 Mar 31;11(7):1179.
MDA-MB-231 cells
500 nM
24 hours
To evaluate the activation effect of AM580 on the RARβ promoter, results showed that AM580 significantly increased the activity of the RARβ promoter.
Cells. 2022 Mar 31;11(7):1179.
H-4-II-E rat hepatoma cells
1 nM to 1 µM
24 hours
To evaluate the effect of AM580 on CYP2C22 mRNA expression, results showed that AM580 significantly upregulated CYP2C22 mRNA levels.
J Lipid Res. 2010 Jul;51(7):1781-92.
Swan71 cells
200 nM
24 to 72 hours
To investigate the induction of RARRES1 expression by AM580 in Swan71 cells. Results showed that AM580 significantly induced RARRES1 expression.
J Exp Clin Cancer Res. 2017 Nov 23;36(1):165.
BeWo cells
200 nM
24 to 72 hours
To investigate the induction of RARRES1 expression by AM580 in BeWo cells. Results showed that AM580 alone did not significantly induce RARRES1 expression, but after pretreatment with 5-aza-2′-deoxycytidine, AM580 significantly increased RARRES1 expression.
J Exp Clin Cancer Res. 2017 Nov 23;36(1):165.
JAR cells
200 nM
24 to 72 hours
To investigate the induction of RARRES1 expression by AM580 in JAR cells. Results showed that AM580 alone did not significantly induce RARRES1 expression, but after pretreatment with 5-aza-2′-deoxycytidine, AM580 significantly increased RARRES1 expression.
J Exp Clin Cancer Res. 2017 Nov 23;36(1):165.
Jeg-3 cells
200 nM
24 to 72 hours
To investigate the induction of RARRES1 expression by AM580 in Jeg-3 cells. Results showed that AM580 alone did not significantly induce RARRES1 expression, but after pretreatment with 5-aza-2′-deoxycytidine, AM580 significantly increased RARRES1 expression.
J Exp Clin Cancer Res. 2017 Nov 23;36(1):165.
MDCK cells
20 µM
48 hours
AM580 significantly inhibited H1N1 virus replication in MDCK cells
Nat Commun. 2019 Jan 10;10(1):120.
Primary trophoblasts
200 nM
48 hours
To investigate the induction of RARRES1 expression by AM580 in primary trophoblasts. Results showed that AM580 significantly induced RARRES1 expression.
J Exp Clin Cancer Res. 2017 Nov 23;36(1):165.
Mouse mammary epithelial cells
200 nM
48 hours
To evaluate the effect of Am580 on CRBP1 expression, results showed that Am580 significantly induced CRBP1 protein expression
Breast Cancer Res. 2012 Aug 24;14(4):R121.
Monocyte-derived dendritic cells (moDCs)
100 nM
6 days
AM580 significantly enhanced the expression levels of ANKRD55 and upregulated IL31RA expression.
Front Immunol. 2022 Jan 17;12:816930.
HEK293T cells
1 µM
6 hours
To assess the metabolic capacity of CYP2C22 for RA, results showed that CYP2C22 converted RA to polar metabolites.
J Lipid Res. 2010 Jul;51(7):1781-92.
Human MCF-7 cells
200 nM
96 hours
To evaluate the effect of Am580 on cell proliferation, results showed that Am580 inhibited cell proliferation
Breast Cancer Res. 2012 Aug 24;14(4):R121.
Human MCF-10A cells
200 nM
96 hours
To evaluate the effect of Am580 on cell proliferation, results showed that Am580 inhibited cell proliferation
Breast Cancer Res. 2012 Aug 24;14(4):R121.
Mouse dorsal root ganglia neurons
5 µM
AM580 activated TRPV1-mediated currents and calcium influx
J Clin Invest. 2013 Sep;123(9):3941-51.
AM580 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Zebrafish (Danio rerio)
Zebrafish embryos
Water exposure
0.001–0.03 µM
0–120 hpf (hours post-fertilization)
To evaluate the effect of AM580 on head skeleton malformations in zebrafish embryos. AM580 significantly increased the Meckel's–palatoquadrate (M–PQ) angle, indicating an effect on head skeleton development.
Arch Toxicol. 2018 Dec;92(12):3549-3564
Mice
MMTV-Myc transgenic mouse model
Oral
0.3 mg/kg/day
Daily administration for 50 weeks
To evaluate the effect of Am580 on mammary tumor growth and metastasis, results showed that Am580 significantly inhibited tumor growth and lung metastasis
Breast Cancer Res. 2012 Aug 24;14(4):R121.
Mice
Tg26 mice (HIV-1 transgenic mice)
Oral
0.3 mg/kg/day
Daily from the age of 4 weeks to 12 weeks
AM580 attenuated proteinuria, glomerulosclerosis, and podocyte proliferation, and restored podocyte differentiation markers
Kidney Int. 2011 Mar;79(6):624-634
Mice
MMTV-neu and MMTV-wnt1 transgenic mice
Dietary addition
0.3mg/kg/day
Daily, for 40 weeks (neu) and 35 weeks (wnt1)
AM580 treatment significantly increased tumor-free survival, reduced tumor incidence and growth of established tumors, and inhibited epithelial hyperplasia
Oncogene. 2010 Jun 24;29(25):3665-76.
HIV-1 transgenic mice
Rapidly progressive renal failure model
Mixed in the animal chow
0.3mg/kg/day
Daily for a total of 5 weeks
AM580 significantly reduced proteinuria, attenuated kidney injury, and improved podocyte differentiation. The renal protective effects were further enhanced when combined with the PDE4 inhibitor roflumilast.
Kidney Int. 2012 May;81(9):856-64
C57BL/6 mice
Experimental autoimmune encephalomyelitis (EAE)
Intraperitoneal injection
1 mg/kg or 2 mg/kg
Administered every other day, starting on day 11 post immunization until day 21 p.i.
AM580 was ineffective in suppressing EAE development and had no significant effect on demyelination and leukocyte infiltration
Cell Mol Immunol. 2019 Aug;16(8):727-729
Zucker diabetic fatty rats
Diabetic cardiomyopathy model
Oral gavage
1 mg/kg/day
Daily for 16 weeks
Am580 attenuated diabetes-induced cardiac dysfunction and the pathological alterations, by improving glucose tolerance and insulin resistance; facilitating Akt activation and glucose utilization, and attenuating oxidative stress and interrelated MAP kinase and NF-κB signaling pathways.
J Mol Cell Cardiol. 2013 Apr;57:106-18
Mice
Trpv1+/+ and Trpv1−/− mice
Intraplantar injection
100 nmol/20 μl
Single injection, observed for 2 hours
AM580 induced paw edema and nociceptive behaviors via TRPV1
J Clin Invest. 2013 Sep;123(9):3941-51.
HDPP4 transgenic mice
MERS-CoV infection model
Intraperitoneal injection
12.5 mg/kg/day
Once daily for 3 days
AM580 significantly improved the survival rate of MERS-CoV-infected mice, reduced body weight loss and lung viral load
Nat Commun. 2019 Jan 10;10(1):120.
5xFAD transgenic mice
Alzheimer's disease model
Intracerebroventricular delivery
28.5 mM
Continuous for 7 or 28 days
Intracerebroventricular delivery of Am580 in 5xFAD mice reduced significantly the fraction of (neurotoxic) iNOS + microglia and increased the fraction of (neuroprotective) TREM2 + microglia. Furthermore, intracerebroventricular delivery of Am580 prevented neurodegeneration induced by microbial TLR agonists.
J Neuroinflammation. 2022 Jan 6;19(1):5.
Rats
Vitamin A-deficient rats
Oral
30 µg AM580
Single dose, euthanized after 6 hours
To evaluate the effect of AM580 on CYP2C22 mRNA expression, results showed that AM580 significantly increased CYP2C22 mRNA levels.
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