Synonym
RO 46-8443; RO46-8443; RO-46-8443; RO 468443; RO-468443; RO468443; RO 46,8443; RO-46,8443; RO46,8443.
IUPAC/Chemical Name
4-(tert-butyl)-N-(6-(2,3-dihydroxypropoxy)-5-(2-methoxyphenoxy)-2-(4-methoxyphenyl)pyrimidin-4-yl)benzenesulfonamide
InChi Key
DRIHNVYRUGBDHI-UHFFFAOYSA-N
InChi Code
InChI=1S/C31H35N3O8S/c1-31(2,3)21-12-16-24(17-13-21)43(37,38)34-29-27(42-26-9-7-6-8-25(26)40-5)30(41-19-22(36)18-35)33-28(32-29)20-10-14-23(39-4)15-11-20/h6-17,22,35-36H,18-19H2,1-5H3,(H,32,33,34)
SMILES Code
COC(C=CC=C1)=C1OC2=C(OCC(O)CO)N=C(C3=CC=C(OC)C=C3)N=C2NS(C4=CC=C(C(C)(C)C)C=C4)(=O)=O
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:
Ro 41-0960 prevents dopaminergic neuron loss induced by L-DOPA in primary rat rostral mesencephalic tegmentum cultures (EC50 = 0.1 µM). Ro 41-0960 (30 mg/kg) potentiates L-DOPA and carbidopa-induced reversal of reserpine-induced akinesias in rats and reserpine-induced catalepsy and hypothermia in mice. It reduces striatal 3-methyl-DOPA levels and increases striatal dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) levels in rats. Ro 41-0960 (150 mg/kg) also reduces fibroid volume in the Eker rat model of uterine fibroids.
In vitro activity:
Ro 46-8443 displays up to 2000-fold selectivity for ETB receptors both in terms of binding inhibitory potency and functional inhibition.
Reference: FEBS Lett. 1996 Mar 25;383(1-2):37-41. https://pubmed.ncbi.nlm.nih.gov/8612786/
In vivo activity:
In normotensive rats, Ro 46-8443 decreased blood pressure, but in SHR and DOCA rats it induced a pressor effect. In DOCA rats and SHR, Ro 46-8443 reveals a predominant influence of endothelial 'vasorelaxant' ETB receptors, while in normotensive rats the prevailing role of ETB receptors seems to be in mediating a vasoconstrictor tone.
Reference: FEBS Lett. 1996 Mar 25;383(1-2):42-5. https://pubmed.ncbi.nlm.nih.gov/8612787/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
250.0 |
410.04 |
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
609.69
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. Breu V, Clozel M, Burri K, Hirth G, Neidhart W, Ramuz H. In vitro characterisation of Ro 46-8443, the first non-peptide antagonist selective for the endothelin ETB receptor. FEBS Lett. 1996 Mar 25;383(1-2):37-41. doi: 10.1016/0014-5793(96)00213-x. PMID: 8612786.
2. Ming Z, Parent R, Thorin E, Lavallée M. Endothelin-dependent tone limits acetylcholine-induced dilation of resistance coronary vessels after blockade of NO formation in conscious dogs. Hypertension. 1998 Nov;32(5):844-8. doi: 10.1161/01.hyp.32.5.844. PMID: 9822442.
3. Clozel M, Breu V. The role of ETB receptors in normotensive and hypertensive rats as revealed by the non-peptide selective ETB receptor antagonist Ro 46-8443. FEBS Lett. 1996 Mar 25;383(1-2):42-5. doi: 10.1016/0014-5793(96)00212-8. PMID: 8612787.
In vitro protocol:
1. Breu V, Clozel M, Burri K, Hirth G, Neidhart W, Ramuz H. In vitro characterisation of Ro 46-8443, the first non-peptide antagonist selective for the endothelin ETB receptor. FEBS Lett. 1996 Mar 25;383(1-2):37-41. doi: 10.1016/0014-5793(96)00213-x. PMID: 8612786.
In vivo protocol:
1. Ming Z, Parent R, Thorin E, Lavallée M. Endothelin-dependent tone limits acetylcholine-induced dilation of resistance coronary vessels after blockade of NO formation in conscious dogs. Hypertension. 1998 Nov;32(5):844-8. doi: 10.1161/01.hyp.32.5.844. PMID: 9822442.
2. Clozel M, Breu V. The role of ETB receptors in normotensive and hypertensive rats as revealed by the non-peptide selective ETB receptor antagonist Ro 46-8443. FEBS Lett. 1996 Mar 25;383(1-2):42-5. doi: 10.1016/0014-5793(96)00212-8. PMID: 8612787.
1: Guimarães CL, Trentin PG, Rae GA. Endothelin ET(B) receptor-mediated mechanisms involved in oleic acid-induced acute lung injury in mice. Clin Sci (Lond). 2002 Aug;103 Suppl 48:340S-344S. PubMed PMID: 12193118.
2: Parent R, Lavallée M. Endothelin-dependent effects limit flow-induced dilation of conductance coronary vessels after blockade of nitric oxide formation in conscious dogs. Cardiovasc Res. 2000 Jan 14;45(2):470-7. PubMed PMID: 10728368.
3: Thorin E, Parent R, Ming Z, Lavallée M. Contribution of endogenous endothelin to large epicardial coronary artery tone in dogs and humans. Am J Physiol. 1999 Aug;277(2 Pt 2):H524-32. PubMed PMID: 10444477.
4: Ming Z, Parent R, Thorin E, Lavallée M. Endothelin-dependent tone limits acetylcholine-induced dilation of resistance coronary vessels after blockade of NO formation in conscious dogs. Hypertension. 1998 Nov;32(5):844-8. PubMed PMID: 9822442.
5: Kempf H, Linares C, Corvol P, Gasc JM. Pharmacological inactivation of the endothelin type A receptor in the early chick embryo: a model of mispatterning of the branchial arch derivatives. Development. 1998 Dec;125(24):4931-41. PubMed PMID: 9811577.
6: Clozel M, Breu V. The role of ETB receptors in normotensive and hypertensive rats as revealed by the non-peptide selective ETB receptor antagonist Ro 46-8443. FEBS Lett. 1996 Mar 25;383(1-2):42-5. PubMed PMID: 8612787.
7: Breu V, Clozel M, Burri K, Hirth G, Neidhart W, Ramuz H. In vitro characterisation of Ro 46-8443, the first non-peptide antagonist selective for the endothelin ETB receptor. FEBS Lett. 1996 Mar 25;383(1-2):37-41. PubMed PMID: 8612786.
8: Clozel M, Gray GA. Are there different ETB receptors mediating constriction and relaxation? J Cardiovasc Pharmacol. 1995;26 Suppl 3:S262-4. PubMed PMID: 8587383.
