Synonym
IRL-2500; IRL 2500; IRL2500.
IUPAC/Chemical Name
((R)-3-([1,1'-biphenyl]-4-yl)-2-(N,3,5-trimethylbenzamido)propanoyl)-L-tryptophan
InChi Key
UZDORQWMYRRLQV-JHOUSYSJSA-N
InChi Code
InChI=1S/C36H35N3O4/c1-23-17-24(2)19-28(18-23)35(41)39(3)33(20-25-13-15-27(16-14-25)26-9-5-4-6-10-26)34(40)38-32(36(42)43)21-29-22-37-31-12-8-7-11-30(29)31/h4-19,22,32-33,37H,20-21H2,1-3H3,(H,38,40)(H,42,43)/t32-,33+/m0/s1
SMILES Code
O=C(N[C@@H](CC1=CNC2=CC=CC=C12)C(O)=O)[C@H](N(C(C3=CC(C)=CC(C)=C3)=O)C)CC4=CC=C(C=C4)C5=CC=CC=C5
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, not in water
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
Biological target:
IRL 2500 is a potent Endothelin receptor antagonist. IRL 2500 shows IC50 values of 1.3 and 94 nM for ETB and ETA receptors, respectively. IRL 2500 inhibits ETB receptor-mediated blood pressure increase and renal vascular resistance in rats in vivo.
In vitro activity:
A caged cell-permeable analog of the ETB-selective antagonist IRL-2500 blocked the ability of intracellular cET-1 to increase [Ca(2+)]n whereas extracellular application of ETA and ETB receptor antagonists did not.
Reference: J Mol Cell Cardiol. 2013 Sep;62:189-202. https://pubmed.ncbi.nlm.nih.gov/23756157/
In vivo activity:
Intracerebroventricular (ICV) administration of BQ788 (ETB antagonist), IRL-2500 (ETB antagonist), or FR139317 (ETA antagonist) prior to cold injury significantly attenuated the increase in brain water content in mice. Bolus administration of BQ788, IRL-2500, or FR139317 also inhibited the cold injury-induced extravasation of Evans blue and albumin. Repeated administration of BQ788 and IRL-2500 beginning at 24 h after cold injury attenuated both the increase in brain water content and extravasation of markers.
Reference: PLoS One. 2014 Jul 7;9(7):e102009. https://pubmed.ncbi.nlm.nih.gov/25000290/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
100.0 |
174.31 |
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
573.69
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. Merlen C, Farhat N, Luo X, Chatenet D, Tadevosyan A, Villeneuve LR, Gillis MA, Nattel S, Thorin E, Fournier A, Allen BG. Intracrine endothelin signaling evokes IP3-dependent increases in nucleoplasmic Ca²⁺ in adult cardiac myocytes. J Mol Cell Cardiol. 2013 Sep;62:189-202. doi: 10.1016/j.yjmcc.2013.05.021. Epub 2013 Jun 10. PMID: 23756157; PMCID: PMC3770605.
2. Michinaga S, Nagase M, Matsuyama E, Yamanaka D, Seno N, Fuka M, Yamamoto Y, Koyama Y. Amelioration of cold injury-induced cortical brain edema formation by selective endothelin ETB receptor antagonists in mice. PLoS One. 2014 Jul 7;9(7):e102009. doi: 10.1371/journal.pone.0102009. PMID: 25000290; PMCID: PMC4084986.
3. Russell FD, Davenport AP. Characterization of the binding of endothelin ETB selective ligands in human and rat heart. Br J Pharmacol. 1996 Oct;119(4):631-6. doi: 10.1111/j.1476-5381.1996.tb15720.x. PMID: 8904635; PMCID: PMC1915765.
In vitro protocol:
1. Merlen C, Farhat N, Luo X, Chatenet D, Tadevosyan A, Villeneuve LR, Gillis MA, Nattel S, Thorin E, Fournier A, Allen BG. Intracrine endothelin signaling evokes IP3-dependent increases in nucleoplasmic Ca²⁺ in adult cardiac myocytes. J Mol Cell Cardiol. 2013 Sep;62:189-202. doi: 10.1016/j.yjmcc.2013.05.021. Epub 2013 Jun 10. PMID: 23756157; PMCID: PMC3770605.
In vivo protocol:
1. Michinaga S, Nagase M, Matsuyama E, Yamanaka D, Seno N, Fuka M, Yamamoto Y, Koyama Y. Amelioration of cold injury-induced cortical brain edema formation by selective endothelin ETB receptor antagonists in mice. PLoS One. 2014 Jul 7;9(7):e102009. doi: 10.1371/journal.pone.0102009. PMID: 25000290; PMCID: PMC4084986.
2. Russell FD, Davenport AP. Characterization of the binding of endothelin ETB selective ligands in human and rat heart. Br J Pharmacol. 1996 Oct;119(4):631-6. doi: 10.1111/j.1476-5381.1996.tb15720.x. PMID: 8904635; PMCID: PMC1915765.
1: Bergdahl A, Valdemarsson S, Adner M, Sun XY, Hedner T, Edvinsson L. Enhanced
endothelin-1-induced contractions in mesenteric arteries from rats with
congestive heart failure: role of ET(B) receptors. Eur J Heart Fail. 2001
Jun;3(3):293-9. PubMed PMID: 11377999.
2: Macchia M, Barontini S, Ceccarelli F, Galoppini C, Giusti L, Hamdan M,
Lucacchini A, Martinelli A, Menchini E, Mazzoni MR, Revoltella RP, Romagnoli F,
Rovero P. Toward the rational development of peptidomimetic analogs of the
C-terminal endothelin hexapeptide: development of a theoretical model. Farmaco.
1998 Aug-Sep;53(8-9):545-56. PubMed PMID: 10081817.
3: Russell FD, Davenport AP. Characterization of the binding of endothelin ETB
selective ligands in human and rat heart. Br J Pharmacol. 1996 Oct;119(4):631-6.
PubMed PMID: 8904635; PubMed Central PMCID: PMC1915765.
