Drug Information

Drug (ID: DG01483) and It's Reported Resistant Information

• Name: U0126
• Synonyms: U0126; 109511-58-2; U-0126; 1,4-Diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto)butadiene; U 0126; UNII-8027P94HLL; CHEBI:64208; (2Z,3Z)-2,3-bis(amino((2-aminophenyl)thio)methylene)succinonitrile; 8027P94HLL; C18H16N6S2; (2Z,3Z)-bis{amino[(2-aminophenyl)sulfanyl]methylidene}butanedinitrile; 109511-58-2 (free); 218601-62-8; FT-1069-1; (2z)-Bis{amino[(2-Aminophenyl)sulfanyl]methylidene}butanedinitrile; (2Z,3Z)-bis{amino[(2-aminophenyl)sulfanyl]methylene}succinonitrile; 1,4-Diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene; (2Z,3Z)-2,3-bis[amino-(2-aminophenyl)sulfanylmethylidene]butanedinitrile; UO-126; BiomolKI_000002; BiomolKI2_000012; BMK1-B2; BSPBio_001224; CHEMBL34704; GTPL5282; Succinonitrile, bis(amino(o-aminophenylthio)methylene)-; CHEBI:90693; CHEBI:91463; Butanedinitrile, bis(amino((2-aminophenyl)thio)methylene)-; DTXSID10892034; HMS1362N05; HMS1792N05; HMS1990N05; HMS3403N05; HMS3414K05; HMS3678K05; AMY31125; BCP01851; EX-A1754; HY-12031A; (2Z,3Z)-2,3-bis[amino-(2-aminophenyl)sulfanyl-methylene]butanedinitrile; (2Z,3Z)-bis({amino[(2-aminophenyl)sulfanyl]methylidene})butanedinitrile; AKOS024456414; ZINC100007148; CCG-100606; LS40194; IDI1_002207; SMP2_000197; NCGC00025029-02; NCGC00025029-03; NCGC00025029-04; CS-0003351; U 126; V2422; A846574; A906530; SR-01000597365; J-002297; Q7863562; SR-01000597365-1; BRD-K18787491-001-04-5; BRD-K46419649-001-01-8; 2,3-Bis(amino((2-aminophenyl)thio)methylene)succinonitrile; Butanedinitrile,2,3-bis[amino[(2-aminophenyl)thio]methylene]-; (2Z,3Z)-2,3-Bis[amino[(2-aminophenyl)thio]methylene]butanedinitrile; Butanedinitrile, bis(amino((2-aminophenyl)thio)methylene)-, (2Z,3Z)-; 5BM
• Indication:
  In total 1 Indication(s)
  Breast cancer [ICD-11: 2C60]; Investigative; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Melanoma [ICD-11: 2C30]; [2]
• Target: Estrogen receptor (ESR); ESR1_HUMAN; [2]
• Formula: 5
• IsoSMILES: C1=CC=C(C(=C1)N)S/C(=C(/C(=C(/SC2=CC=CC=C2N)\\N)/C#N)\\C#N)/N
• InChI: InChI=1S/C18H16N6S2/c19-9-11(17(23)25-15-7-3-1-5-13(15)21)12(10-20)18(24)26-16-8-4-2-6-14(16)22/h1-8H,21-24H2/b17-11+,18-12+
• InChIKey: DVEXZJFMOKTQEZ-JYFOCSDGSA-N
• PubChem CID: 3006531
• ChEBI ID: CHEBI:64208
• TTD Drug ID: D04VFJ

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

Acute lymphocytic leukemia [ICD-11: 2B33]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) [1]

• Molecule Alteration: Missense mutation; p.E76K (c.226G>A)
• Sensitive Disease: Acute lymphocytic leukemia [ICD-11: 2B33.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Experiment for Molecule Alteration: Immunoblotting analysis
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: The missense mutation p.E76K (c.226G>A) in gene PTPN11 cause the sensitivity of U0126 by unusual activation of pro-survival pathway

Melanoma [ICD-11: 2C30]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [2]

• Molecule Alteration: Missense mutation; p.G469E (c.1406G>A)
• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Human melanoma tissue; N.A.
• In Vivo Model: (SCID) CB-17 mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.G469E (c.1406G>A) in gene BRAF cause the resistance of U0126 by unusual activation of pro-survival pathway

Key Molecule: Serine/threonine-protein kinase B-raf (BRAF) [2]

• Molecule Alteration: Missense mutation; p.D594G (c.1781A>G)
• Resistant Disease: Melanoma [ICD-11: 2C30.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Human melanoma tissue; N.A.
• In Vivo Model: (SCID) CB-17 mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The missense mutation p.D594G (c.1781A>G) in gene BRAF cause the resistance of U0126 by unusual activation of pro-survival pathway

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) [3]

• Molecule Alteration: Missense mutation; p.Q209L (c.626A>T)
• Sensitive Disease: Uveal melanoma [ICD-11: 2D0Y.0]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Eyeball; N.A.
• Experiment for Molecule Alteration: DNA sequencing assay
• Experiment for Drug Resistance: CyQUANT Cell (Invitrogen) proliferation assay
• Mechanism Description: The missense mutation p.Q209L (c.626A>T) in gene GNAQ cause the sensitivity of U0126 by unusual activation of pro-survival pathway

References

• Ref 1: Shp2E76K mutant confers cytokine-independent survival of TF-1 myeloid cells by up-regulating Bcl-XLJ Biol Chem. 2007 Dec 14;282(50):36463-73. doi: 10.1074/jbc.M705789200. Epub 2007 Oct 17.
• Ref 2: CRAF inhibition induces apoptosis in melanoma cells with non-V600E BRAF mutationsOncogene. 2009 Jan 8;28(1):85-94. doi: 10.1038/onc.2008.362. Epub 2008 Sep 15.
• Ref 3: Frequent somatic mutations of GNAQ in uveal melanoma and blue naeviNature. 2009 Jan 29;457(7229):599-602. doi: 10.1038/nature07586. Epub 2008 Dec 10.