Synonym
MRT-83; MRT 83; MRT83.
IUPAC/Chemical Name
N-(2-methyl-5-(3-(3,4,5-trimethoxybenzoyl)guanidino)phenyl)-[1,1'-biphenyl]-4-carboxamide hydrochloride
InChi Key
ZOQUUTBPNBYISX-UHFFFAOYSA-N
InChi Code
InChI=1S/C31H30N4O5.ClH/c1-19-10-15-24(33-31(32)35-30(37)23-16-26(38-2)28(40-4)27(17-23)39-3)18-25(19)34-29(36)22-13-11-21(12-14-22)20-8-6-5-7-9-20;/h5-18H,1-4H3,(H,34,36)(H3,32,33,35,37);1H
SMILES Code
O=C(NC(NC1=CC=C(C)C(NC(C2=CC=C(C3=CC=CC=C3)C=C2)=O)=C1)=N)C4=CC(OC)=C(OC)C(OC)=C4.[H]Cl
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:
MRT-83 (hydrochloride) is the potent antagonist of Smoothened (Smo) receptor.
In vitro activity:
MRT-83 blocks Hedgehog (Hh) signaling in various assays with an IC50 in the nanomolar range, showing greater potency than the reference Smo antagonist cyclopamine. MRT-83 inhibits Bodipy-cyclopamine binding to human and mouse Smo but does not modify Wnt signaling in human embryonic kidney 293 transiently transfected with a Tcf/Lef-dependent Firefly luciferase reporter together with a Renilla reniformis luciferase control reporter.
Reference: Mol Pharmacol. 2011 Mar;79(3):453-60. https://pubmed.ncbi.nlm.nih.gov/21177415/
In vivo activity:
MRT-83 abrogates the agonist-induced trafficking of endogenous mouse or human Smo to the primary cilium of C3H10T1/2 or NT2 cells that derive from a pluripotent testicular carcinoma. Stereotaxic injection into the lateral ventricle of adult mice of MRT-83 but not of a structurally related compound inactive at Smo abolished up-regulation of Patched transcription induced by Sonic Hedgehog in the neighboring subventricular zone. These data demonstrate that MRT-83 efficiently antagonizes Hh signaling in vivo.
Reference: Mol Pharmacol. 2011 Mar;79(3):453-60. https://pubmed.ncbi.nlm.nih.gov/21177415/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
250.0 |
434.74 |
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
575.06
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:
Roudaut H, Traiffort E, Gorojankina T, Vincent L, Faure H, Schoenfelder A, Mann A, Manetti F, Solinas A, Taddei M, Ruat M. Identification and mechanism of action of the acylguanidine MRT-83, a novel potent Smoothened antagonist. Mol Pharmacol. 2011 Mar;79(3):453-60. doi: 10.1124/mol.110.069708. Epub 2010 Dec 21. PMID: 21177415.
In vitro protocol:
Roudaut H, Traiffort E, Gorojankina T, Vincent L, Faure H, Schoenfelder A, Mann A, Manetti F, Solinas A, Taddei M, Ruat M. Identification and mechanism of action of the acylguanidine MRT-83, a novel potent Smoothened antagonist. Mol Pharmacol. 2011 Mar;79(3):453-60. doi: 10.1124/mol.110.069708. Epub 2010 Dec 21. PMID: 21177415.
In vivo protocol:
Roudaut H, Traiffort E, Gorojankina T, Vincent L, Faure H, Schoenfelder A, Mann A, Manetti F, Solinas A, Taddei M, Ruat M. Identification and mechanism of action of the acylguanidine MRT-83, a novel potent Smoothened antagonist. Mol Pharmacol. 2011 Mar;79(3):453-60. doi: 10.1124/mol.110.069708. Epub 2010 Dec 21. PMID: 21177415.
1: Gorojankina T, Hoch L, Faure H, Roudaut H, Traiffort E, Schoenfelder A, Girard
N, Mann A, Manetti F, Solinas A, Petricci E, Taddei M, Ruat M. Discovery,
molecular and pharmacological characterization of GSA-10, a novel small-molecule
positive modulator of Smoothened. Mol Pharmacol. 2013 May;83(5):1020-9. doi:
10.1124/mol.112.084590. Epub 2013 Feb 28. Erratum in: Mol Pharmacol. 2013
Aug;84(2):303. PubMed PMID: 23448715.
2: Solinas A, Faure H, Roudaut H, Traiffort E, Schoenfelder A, Mann A, Manetti F,
Taddei M, Ruat M. Acylthiourea, acylurea, and acylguanidine derivatives with
potent hedgehog inhibiting activity. J Med Chem. 2012 Feb 23;55(4):1559-71. doi:
10.1021/jm2013369. Epub 2012 Feb 10. PubMed PMID: 22268551.
3: Roudaut H, Traiffort E, Gorojankina T, Vincent L, Faure H, Schoenfelder A,
Mann A, Manetti F, Solinas A, Taddei M, Ruat M. Identification and mechanism of
action of the acylguanidine MRT-83, a novel potent Smoothened antagonist. Mol
Pharmacol. 2011 Mar;79(3):453-60. doi: 10.1124/mol.110.069708. Epub 2010 Dec 21.
PubMed PMID: 21177415.
