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
• 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]
• Target: .; NOUNIPROTAC; [1]
• 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

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Smoothened homolog (SMO) [1]

• Molecule Alteration: Missense mutation; p.V329F (c.985_987delGTGinsTTT)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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 blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; [3H]-TAK-441 radioligand membrane binding assay

Key Molecule: Smoothened homolog (SMO) [1]

• Molecule Alteration: Missense mutation; p.D384A (c.1151A>C)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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 blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; [3H]-TAK-441 radioligand membrane binding assay

Key Molecule: Smoothened homolog (SMO) [1]

• Molecule Alteration: Missense mutation; p.Y394A (c.1180_1181delTAinsGC)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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 blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; [3H]-TAK-441 radioligand membrane binding assay

Key Molecule: Smoothened homolog (SMO) [1]

• Molecule Alteration: Missense mutation; p.T466F (c.1396_1397delACinsTT)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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 blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; [3H]-TAK-441 radioligand membrane binding assay

Key Molecule: Smoothened homolog (SMO) [1]

• Molecule Alteration: Missense mutation; p.E518K (c.1552G>A)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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 blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; [3H]-TAK-441 radioligand membrane binding assay

Key Molecule: Smoothened homolog (SMO) [1]

• Molecule Alteration: Missense mutation; p.M525G (c.1573_1574delATinsGG)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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 blotting analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; [3H]-TAK-441 radioligand membrane binding assay

Key Molecule: Smoothened homolog (SMO) [1]

• Molecule Alteration: Missense mutation; p.L325F (c.973_975delCTGinsTTT)
• Resistant Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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 blotting 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)

Key Molecule: Smoothened homolog (SMO) [1]

• Molecule Alteration: Missense mutation; p.R400A (c.1198_1199delCGinsGC)
• Sensitive Disease: Solid tumour/cancer [ICD-11: 2A00-2F9Z]
• 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 blotting 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.