Synonym
BAR-502; BAR 502; BAR502
IUPAC/Chemical Name
(3R,5S,6R,7R,8S,9S,10S,13R,14S,17R)-6-ethyl-17-((R)-4-hydroxybutan-2-yl)-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthrene-3,7-diol
InChi Key
HYCMOIGNYNCMRH-APIYUPOTSA-N
InChi Code
InChI=1S/C25H44O3/c1-5-17-21-14-16(27)8-11-25(21,4)20-9-12-24(3)18(15(2)10-13-26)6-7-19(24)22(20)23(17)28/h15-23,26-28H,5-14H2,1-4H3/t15-,16-,17-,18-,19+,20+,21+,22+,23-,24-,25-/m1/s1
SMILES Code
O[C@@H]1CC[C@]2(C)[C@@]3([H])CC[C@]4(C)[C@@H]([C@@H](CCO)C)CC[C@@]4([H])[C@]3([H])[C@H](O)[C@H](CC)[C@]2([H])C1
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Non-alcoholic steatohepatitis (NASH) is a highly prevalent chronic liver disease.
Biological target:
BAR502 is a dual FXR and GPBAR1 agonist with IC50 values of 2 μM and 0.4 μM, respectively.
In vivo activity:
Whether BAR502, a non-bile acid, steroidal dual ligand for FXR and GPBAR1, reverses steato-hepatitis in mice fed a high fat diet (HFD) and fructose was investigated. After 9 week, mice on HFD gained ≈30% of b.w (P < 0.01 versus naïve) and were insulin resistant. These overweighting and insulin resistant mice were randomized to receive HFD or HFD in combination with BAR502. After 18 weeks, HFD mice developed NASH like features with severe steato-hepatitis and fibrosis, increased hepatic content of triacylglycerol and cholesterol and expression of SREPB1c, FAS, ApoC2, PPARα and γ, α-SMA, α1 collagen and MCP1 mRNAs. Treatment with BAR502 caused a ≈10% reduction of b.w., increased insulin sensitivity and circulating levels of HDL, while reduced steatosis, inflammatory and fibrosis scores and liver expression of SREPB1c, FAS, PPARγ, CD36 and CYP7A1 mRNA. BAR502 increased the expression of SHP and ABCG5 in the liver and SHP, FGF15 and GLP1 in intestine. BAR502 promoted the browning of epWAT and reduced liver fibrosis induced by CCl4. In summary, BAR502, a dual FXR and GPBAR1 agonist, protects against liver damage caused by HFD by promoting the browning of adipose tissue.
Reference: Sci Rep. 2017 Feb 16;7:42801. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5311892/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
35.0 |
89.14 |
| Ethanol |
51.0 |
129.89 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
392.62
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Carino A, Cipriani S, Marchianò S, Biagioli M, Santorelli C, Donini A, Zampella A, Monti MC, Fiorucci S. BAR502, a dual FXR and GPBAR1 agonist, promotes browning of white adipose tissue and reverses liver steatosis and fibrosis. Sci Rep. 2017 Feb 16;7:42801. doi: 10.1038/srep42801. PMID: 28202906; PMCID: PMC5311892.
2. Carino A, Marchianò S, Biagioli M, Fiorucci C, Zampella A, Monti MC, Morretta E, Bordoni M, Di Giorgio C, Roselli R, Ricci P, Distrutti E, Fiorucci S. Transcriptome Analysis of Dual FXR and GPBAR1 Agonism in Rodent Model of NASH Reveals Modulation of Lipid Droplets Formation. Nutrients. 2019 May 21;11(5):1132. doi: 10.3390/nu11051132. PMID: 31117231; PMCID: PMC6567134.
In vivo protocol:
1. Carino A, Cipriani S, Marchianò S, Biagioli M, Santorelli C, Donini A, Zampella A, Monti MC, Fiorucci S. BAR502, a dual FXR and GPBAR1 agonist, promotes browning of white adipose tissue and reverses liver steatosis and fibrosis. Sci Rep. 2017 Feb 16;7:42801. doi: 10.1038/srep42801. PMID: 28202906; PMCID: PMC5311892.
2. Carino A, Marchianò S, Biagioli M, Fiorucci C, Zampella A, Monti MC, Morretta E, Bordoni M, Di Giorgio C, Roselli R, Ricci P, Distrutti E, Fiorucci S. Transcriptome Analysis of Dual FXR and GPBAR1 Agonism in Rodent Model of NASH Reveals Modulation of Lipid Droplets Formation. Nutrients. 2019 May 21;11(5):1132. doi: 10.3390/nu11051132. PMID: 31117231; PMCID: PMC6567134.
1: Carino A, Cipriani S, Marchianò S, Biagioli M, Santorelli C, Donini A,
Zampella A, Monti MC, Fiorucci S. BAR502, a dual FXR and GPBAR1 agonist, promotes
browning of white adipose tissue and reverses liver steatosis and fibrosis. Sci
Rep. 2017 Feb 16;7:42801. doi: 10.1038/srep42801. PubMed PMID: 28202906; PubMed
Central PMCID: PMC5311892.
2: Cipriani S, Renga B, D'Amore C, Simonetti M, De Tursi AA, Carino A, Monti MC,
Sepe V, Zampella A, Fiorucci S. Impaired Itching Perception in Murine Models of
Cholestasis Is Supported by Dysregulation of GPBAR1 Signaling. PLoS One. 2015 Jul
15;10(7):e0129866. doi: 10.1371/journal.pone.0129866. eCollection 2015. PubMed
PMID: 26177448; PubMed Central PMCID: PMC4503431.
