Drug Information

Drug (ID: DG01510) and It's Reported Resistant Information

• Name: Napabucasin
• Synonyms: Napabucasin; 83280-65-3; 2-Acetylfuro-1,4-naphthoquinone; BBI608; 2-acetylnaphtho[2,3-b]furan-4,9-dione; 2-acetylbenzo[f][1]benzofuran-4,9-dione; BBI-608; UNII-Z1HHM49K7O; Napabucasin (BBI608); 2-Acetylfuranonaphthoquinone; Z1HHM49K7O; BBI 608; 2-Acetyl-4H,9H-naphtho[2,3-b]furan-4,9-dione; 2-Acetylnaphtho(2,3-b)furan-4,9-dione; Napabucasin [USAN:INN]; FNQ; Napabucasin; BBI608; CHEMBL64130; Napabucasin (JAN/USAN/INN); SCHEMBL1883845; GTPL11358; AMY27812; BCP07628; EX-A1314; BDBM50366597; MFCD28155270; NSC788900; s7977; ZINC13306865; AKOS027470201; CCG-266871; CS-1747; DB12155; NSC-788900; 2-acetyl naphtho2,3-bfuran-4,9-dione; AC-32935; AS-60519; HY-13919; 2-Acetyl-naphtho[2,3-b]furan-4,9-dione; A13474; D10717; F17379; Q27294876
• Indication:
  In total 1 Indication(s)
  Hepatitis C virus infection [ICD-11: 1E50-1E51]; Phase 3; [1]
• Target: Hepatitis C virus Serine protease NS3/4A (HCV NS3/4A); POLG_HCV1; [1]
• Formula: 1
• IsoSMILES: CC(=O)C1=CC2=C(O1)C(=O)C3=CC=CC=C3C2=O
• InChI: InChI=1S/C14H8O4/c1-7(15)11-6-10-12(16)8-4-2-3-5-9(8)13(17)14(10)18-11/h2-6H,1H3
• InChIKey: DPHUWDIXHNQOSY-UHFFFAOYSA-N
• PubChem CID: 10331844
• TTD Drug ID: D0V3YT
• DrugBank ID: DB12155

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]

• Molecule Alteration: Missense mutation; p.R248Q (c.743G>A)
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: JAKT2/STAT3 signaling pathway; Inhibition; hsa04030
• In Vitro Model: HT29 Cells; Colon; Homo sapiens (Human); CVCL_A8EZ
• In Vitro Model: SW480 cells; Colon; Homo sapiens (Human); CVCL_0546
• In Vitro Model: H1299 cells; Lung; Homo sapiens (Human); CVCL_0060
• In Vitro Model: SW1116 cells; Colon; Homo sapiens (Human); CVCL_0544
• In Vitro Model: LS1034 cells; Colon; Homo sapiens (Human); CVCL_1382
• In Vitro Model: SW48 cells; Colon; Homo sapiens (Human); CVCL_1724
• In Vitro Model: Colo320 cells; Colon; Homo sapiens (Human); CVCL_1989
• In Vitro Model: SW837 cells; Colon; Homo sapiens (Human); CVCL_1729
• In Vitro Model: DLD-1 cells; Colon; Homo sapiens (Human); CVCL_0248
• In Vitro Model: SW1463 cells; Rectum; Homo sapiens (Human); CVCL_1718
• In Vivo Model: C57BL/6 mouse model; Mus musculus
• Experiment for Molecule Alteration: BCA protein assay; SDS-PAGE assay
• Experiment for Drug Resistance: Scratch assay; Transwell migration assay; Fluorescent in situ hybridization assay
• Mechanism Description: The most common p53 mutant R248Q (mutp53) enhances Stat3 activation by binding to Stat3 and displacing SHP2 in colorectal cancer cells. Reduction of mutp53 genetically or by using the HSP90 inhibitor 17AAG reduces Stat3 signaling and the growth of mutp53-driven tumors.

References

• Ref 1: Therapeutic Ablation of Gain-of-Function Mutant p53 in Colorectal Cancer Inhibits Stat3-Mediated Tumor Growth and InvasionCancer Cell. 2018 Aug 13;34(2):298-314.e7. doi: 10.1016/j.ccell.2018.07.004.