Drug Information

Drug (ID: DG01492) and It's Reported Resistant Information

• Name: NSC59984
• Synonyms: NSC59984; 803647-40-7; NSC 59984; (E)-1-(4-methylpiperazin-1-yl)-3-(5-nitrofuran-2-yl)prop-2-en-1-one; NSC-59984; MLS000737358; SMR000528276; 1-(4-methylpiperazin-1-yl)-3-(5-nitrofuran-2-yl)prop-2-en-1-one; CHEMBL1979662; SCHEMBL17071991; SCHEMBL17654893; BDBM96260; cid_5356520; EX-A776; HMS2885J20; BCP16647; MFCD29905462; s8106; ZINC59727553; NSC59984,NCI59984; CCG-267098; CS-5382; AC-32965; BS-18159; HY-19726; NSC59984, >=98% (HPLC); A13413; J-690353; (E)-1-(4-methylpiperazino)-3-(5-nitro-2-furyl)prop-2-en-1-one; (E)-1-(4-methyl-1-piperazinyl)-3-(5-nitro-2-furanyl)-2-propen-1-one; N-[1,3-Dimethyl-2-oxo-6-(1-pyrrolidinyl)-2,3-dihydro-1H-benzimidazol-5-yl]-2-methoxybenzamide
• Formula: 2
• IsoSMILES: CN1CCN(CC1)C(=O)/C=C/C2=CC=C(O2)[N+](=O)[O-]
• InChI: InChI=1S/C12H15N3O4/c1-13-6-8-14(9-7-13)11(16)4-2-10-3-5-12(19-10)15(17)18/h2-5H,6-9H2,1H3/b4-2+
• InChIKey: QKTRIGNWBRHBFV-DUXPYHPUSA-N
• PubChem CID: 5356520

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

Colorectal cancer [ICD-11: 2B91]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Cellular tumor antigen p53 (TP53) [1]

• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Molecule Alteration: Missense mutation; p.R175H (c.524G>A)
• Wild Type Structure: Method: X-ray diffraction; Resolution: 2.37 Å; PDB: 6VR1
• Mutant Type Structure: Method: X-ray diffraction; Resolution: 2.38 Å; PDB: 6VR5

RMSD: 0.18; TM score: 0.89418; Amino acid change: R175H

• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW480 cells; Colon; Homo sapiens (Human); CVCL_0546
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: DLD-1 cells; Colon; Homo sapiens (Human); CVCL_0248
• In Vitro Model: RXF393 cells; Kidney; Homo sapiens (Human); CVCL_1673
• In Vitro Model: MRC5 cells; Fetal lung; Homo sapiens (Human); CVCL_0440
• In Vitro Model: Wi38 cells; Fetal lung; Homo sapiens (Human); CVCL_0579
• In Vitro Model: Hop92 cells; Lung; Homo sapiens (Human); CVCL_1286
• In Vivo Model: Female CRL nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Semi-quantitative RT-PCR; Western blot analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; Colony formation assay

Key Molecule: Cellular tumor antigen p53 (TP53) [1]

• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Molecule Alteration: Missense mutation; p.R175L (c.524G>T)
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SW480 cells; Colon; Homo sapiens (Human); CVCL_0546
• In Vitro Model: HCT116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: DLD-1 cells; Colon; Homo sapiens (Human); CVCL_0248
• In Vitro Model: RXF393 cells; Kidney; Homo sapiens (Human); CVCL_1673
• In Vitro Model: MRC5 cells; Fetal lung; Homo sapiens (Human); CVCL_0440
• In Vitro Model: Wi38 cells; Fetal lung; Homo sapiens (Human); CVCL_0579
• In Vitro Model: Hop92 cells; Lung; Homo sapiens (Human); CVCL_1286
• In Vivo Model: Female CRL nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Semi-quantitative RT-PCR; Western blot analysis
• Experiment for Drug Resistance: CellTiter-Glo assay; Colony formation assay

References

• Ref 1: Small-Molecule NSC59984 Restores p53 Pathway Signaling and Antitumor Effects against Colorectal Cancer via p73 Activation and Degradation of Mutant p53Cancer Res. 2015 Sep 15;75(18):3842-52. doi: 10.1158/0008-5472.CAN-13-1079. Epub 2015 Aug 20.