Drug Information

Drug (ID: DG01508) and It's Reported Resistant Information

• Name: Sotrastaurin
• Synonyms: Sotrastaurin; 425637-18-9; AEB071; Sotrastaurin (AEB071); AEB-071; 3-(1H-Indol-3-yl)-4-(2-(4-methylpiperazin-1-yl)quinazolin-4-yl)-1H-pyrrole-2,5-dione; UNII-7I279E1NZ8; 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione; NVP-AEB071; CHEBI:90531; 7I279E1NZ8; AEB 071; 3-(1h-Indol-3-Yl)-4-[2-(4-Methylpiperazin-1-Yl)quinazolin-4-Yl]-1h-Pyrrole-2,5-Dione; Sotrastaurin [USAN:INN]; sotrastaurina; sotrastaurine; sotrastaurinum; Kinome_2717; Sotrastaurin (USAN/INN); NVP-AEB-071; CHEMBL565612; GTPL7946; SCHEMBL2500835; BDBM33971; DTXSID70915192; HMS3656D10; HMS3673M05; HMS3744G03; AMY10736; AOB87472; BCP07456; EX-A2802; ZINC3973984; NSC766819; NSC800935; s2791; CCG-264999; CS-0090; DB12369; NSC-766819; NSC-800935; SB16638; NCGC00238621-01; NCGC00238621-09; AC-32050; AS-56373; HY-10343; SW220235-1; Y6229; D09671; L10095; A857807; Q26331952; 1H-Pyrrole-2,5-dione, 3-(1H-indol-3-yl)-4-(2-(4-methyl-1-piperazinyl)-4-quinazolinyl)-; 3-(1H-indol-3-yl)-4-[2-(4-methyl-piperazin-1-yl)-quinazolin-4-yl]-pyrrole-2,5-dione; 1058706-31-2; 5-Hydroxy-4-(1H-indol-3-yl)-3-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]-2H-pyrrol-2-one; 949935-06-2; LW4
• Target: .; NOUNIPROTAC; [1]
• Formula: 3
• IsoSMILES: CN1CCN(CC1)C2=NC3=CC=CC=C3C(=N2)C4=C(C(=O)NC4=O)C5=CNC6=CC=CC=C65
• InChI: InChI=1S/C25H22N6O2/c1-30-10-12-31(13-11-30)25-27-19-9-5-3-7-16(19)22(28-25)21-20(23(32)29-24(21)33)17-14-26-18-8-4-2-6-15(17)18/h2-9,14,26H,10-13H2,1H3,(H,29,32,33)
• InChIKey: OAVGBZOFDPFGPJ-UHFFFAOYSA-N
• PubChem CID: 10296883
• DrugBank ID: DB12369

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

Uveal melanoma [ICD-11: 2D0Y]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Guanine nucleotide-binding protein alpha-q (GNAQ) [1]

• Molecule Alteration: Missense mutation; p.Q209P (c.626A>C)
• Sensitive Disease: Uveal melanoma [ICD-11: 2D0Y.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Omm13 cells; N.A.; .; N.A.
• In Vitro Model: Ocm3 cells; Skin; Homo sapiens (Human); CVCL_6937
• In Vitro Model: Ocm1 cells; Hypodermis; Homo sapiens (Human); CVCL_6934
• In Vitro Model: Mel285 cells; Skin; Homo sapiens (Human); CVCL_C303
• In Vitro Model: Mel202 cells; Eye; Homo sapiens (Human); CVCL_C301
• In Vitro Model: C918 cells; Skin; Homo sapiens (Human); CVCL_8471
• In Vitro Model: 92-1 cells; Bladder; Homo sapiens (Human); CVCL_W909
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: V-FITC assay
• Mechanism Description: The missense mutation p.Q209P (c.626A>C) in gene GNAQ cause the sensitivity of Sotrastaurin by unusual activation of pro-survival pathway

Key Molecule: Guanine nucleotide-binding protein alpha-q (GNAQ) [2]

• Molecule Alteration: Missense mutation; p.Q209L (c.626A>T)
• Sensitive Disease: Uveal melanoma [ICD-11: 2D0Y.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: OMM-GN11; N.A.; Mus musculus (Mouse); N.A.
• In Vitro Model: OMM13; N.A.; .; N.A.
• In Vitro Model: Mel202; Eye; Homo sapiens (Human); CVCL_C301
• In Vitro Model: GNAQ cells; N.A.; .; N.A.
• In Vitro Model: Mel270 cells; Skin; Homo sapiens (Human); CVCL_C302
• In Vitro Model: GNA11 cells; N.A.; .; N.A.
• In Vitro Model: UPMD-1 cells; Skin; Homo sapiens (Human); CVCL_C297
• In Vitro Model: 92-1 cells; Bladder; Homo sapiens (Human); CVCL_W909
• In Vitro Model: Mel202; Eye; Homo sapiens (Human); CVCL_C301
• In Vivo Model: C57/BL6 mouse model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Cell proliferation assay

References

• Ref 1: Protein kinase C inhibitor AEB071 targets ocular melanoma harboring GNAQ mutations via effects on the PKC/Erk1/2 and PKC/NF-kB pathwaysMol Cancer Ther. 2012 Sep;11(9):1905-14. doi: 10.1158/1535-7163.MCT-12-0121. Epub 2012 May 31.
• Ref 2: Combined PKC and MEK inhibition in uveal melanoma with GNAQ and GNA11 mutationsOncogene. 2014 Sep 25;33(39):4724-34. doi: 10.1038/onc.2013.418. Epub 2013 Oct 21.