Drug Information

Drug (ID: DG01673) and It's Reported Resistant Information
Name
MRT-92
Synonyms
MRT-92; CHEMBL4302587; SCHEMBL14809192; GTPL10332; 3,4,5-trimethoxy-N-[N'-[4-methyl-3-[[4-(2-phenylethyl)benzoyl]amino]phenyl]carbamimidoyl]benzamide
    Click to Show/Hide
Structure
Drug Resistance Disease(s)
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
[1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
11
IsoSMILES
CC1=C(C=C(C=C1)N=C(N)NC(=O)C2=CC(=C(C(=C2)OC)OC)OC)NC(=O)C3=CC=C(C=C3)CCC4=CC=CC=C4
InChI
InChI=1S/C33H34N4O5/c1-21-10-17-26(35-33(34)37-32(39)25-18-28(40-2)30(42-4)29(19-25)41-3)20-27(21)36-31(38)24-15-13-23(14-16-24)12-11-22-8-6-5-7-9-22/h5-10,13-20H,11-12H2,1-4H3,(H,36,38)(H3,34,35,37,39)
InChIKey
TVUOHEUCOWBVRU-UHFFFAOYSA-N
PubChem CID
136235465
Type(s) of Resistant Mechanism of This Drug
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
Click to Show/Hide the Resistance Disease of This Class
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Smoothened homolog (SMO) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.V329F (c.985_987delGTGinsTTT)
 Molecule Info 
Wild Type Structure Method: Electron microscopy Resolution: 3.14  Å
PDB: 6XBM
Mutant Type Structure Method: X-ray diffraction Resolution: 3.00  Å
PDB: 7ZI0
   Download The Information of Sequence       Download The Structure File   
RMSD: 2.44
TM score: 0.90019
Amino acid change:
V329F
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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Click to Show/Hide the Structure
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CellTiter-Glo assay; [3H]-TAK-441 radioligand membrane binding assay
Key Molecule: Smoothened homolog (SMO) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.D384A (c.1151A>C)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CellTiter-Glo assay; [3H]-TAK-441 radioligand membrane binding assay
Key Molecule: Smoothened homolog (SMO) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.Y394A (c.1180_1181delTAinsGC)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CellTiter-Glo assay; [3H]-TAK-441 radioligand membrane binding assay
Key Molecule: Smoothened homolog (SMO) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.T466F (c.1396_1397delACinsTT)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CellTiter-Glo assay; [3H]-TAK-441 radioligand membrane binding assay
Key Molecule: Smoothened homolog (SMO) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.E518K (c.1552G>A)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CellTiter-Glo assay; [3H]-TAK-441 radioligand membrane binding assay
Key Molecule: Smoothened homolog (SMO) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.M525G (c.1573_1574delATinsGG)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CellTiter-Glo assay; [3H]-TAK-441 radioligand membrane binding assay
Key Molecule: Smoothened homolog (SMO) [1]
Resistant Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.L325F (c.973_975delCTGinsTTT)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CellTiter-Glo assay; [3H]-TAK-441 radioligand membrane binding assay
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Smoothened homolog (SMO) [1]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.R400A (c.1198_1199delCGinsGC)
 Molecule Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CellTiter-Glo assay; [3H]-TAK-441 radioligand membrane binding assay
References
Ref 1 MRT-92 inhibits Hedgehog signaling by blocking overlapping binding sites in the transmembrane domain of the Smoothened receptorFASEB J. 2015 May;29(5):1817-29. doi: 10.1096/fj.14-267849. Epub 2015 Jan 30.

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