Drug Information

Drug (ID: DG00334) and It's Reported Resistant Information

• Name: Veliparib dihydrochloride
• Synonyms: Veliparib; 912444-00-9; ABT-888; ABT 888; ABT-888 (Veliparib); Veliparib (ABT-888); ABT888; UNII-01O4K0631N; 2-[(2R)-2-Methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide; CHEBI:62880; 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide; (R)-2-(2-methylpyrrolidin-2-yl)-1H-benzo[d]imidazole-4-carboxamide; 01O4K0631N; 2-[(2R)-2-Methylpyrrolidin-2-yl]-1H-benimidazole-4-; (2r)-2-(7-Carbamoyl-1h-Benzimidazol-2-Yl)-2-Methylpyrrolidinium; Veliparib dihydrochloride
• Indication:
  In total 5 Indication(s)
  Breast cancer [ICD-11: 2C60]; Phase 3; [1]
  Lung cancer [ICD-11: 2C25]; Phase 3; [1]
  Malignant mesenchymal neoplasm [ICD-11: 2B5D-2B5Y]; Phase 3; [1]
  Ovarian cancer [ICD-11: 2C73]; Phase 3; [1]
  Melanoma [ICD-11: 2C30]; Phase 2; [1]
• Target: Poly [ADP-ribose] polymerase (PARP); NOUNIPROTAC; [1]
• Formula: C13H18Cl2N4O
• IsoSMILES: C[C@@]1(CCCN1)C2=NC3=C(C=CC=C3N2)C(=O)N.Cl.Cl
• InChI: 1S/C13H16N4O.2ClH/c1-13(6-3-7-15-13)12-16-9-5-2-4-8(11(14)18)10(9)17-12;;/h2,4-5,15H,3,6-7H2,1H3,(H2,14,18)(H,16,17);2*1H/t13-;;/m1../s1
• InChIKey: DSBSVDCHFMEYBX-FFXKMJQXSA-N
• PubChem CID: 45480520
• TTD Drug ID: D0Q7UD
• DrugBank ID: DB07232

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Prostate cancer [ICD-11: 2C82]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Prostate cancer associated transcript 1 (PCAT1) [1]

• Molecule Alteration: Expression; Up-regulation
• Sensitive Disease: Prostate cancer [ICD-11: 2C82.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: DU-145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• In Vitro Model: LNCaP cells; Prostate; Homo sapiens (Human); CVCL_0395
• In Vitro Model: PC3 cells; Prostate; Homo sapiens (Human); CVCL_0035
• In Vitro Model: RWPE cells; Prostate; Homo sapiens (Human); CVCL_1736
• In Vivo Model: SCID nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qPCR
• Experiment for Drug Resistance: WST assay
• Mechanism Description: PCAT-1 expressing cells exhibit a BRCA-like phenotype, resulting in cell sensitization to PARP1 inhibitors. In human prostate cancer tissues, high PCAT-1 expression predicts for low BRCA2 expression, supporting our observations in model systems.

References

• Ref 1: PCAT-1, a long noncoding RNA, regulates BRCA2 and controls homologous recombination in cancer. Cancer Res. 2014 Mar 15;74(6):1651-60. doi: 10.1158/0008-5472.CAN-13-3159. Epub 2014 Jan 28.