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]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Ovarian cancer [ICD-11: 2C73]; [2]
• 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

  ADTT: Aberration of the Drug's Therapeutic Target

  EADR: Epigenetic Alteration of DNA, RNA or Protein

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Ovarian cancer [ICD-11: 2C73]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Breast cancer type 1 susceptibility protein (BRCA1) [2]

• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Molecule Alteration: Mutations; .
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: UWB1.289 cells; Ovary; Homo sapiens (Human); CVCL_B079
• Experiment for Molecule Alteration: Whole exome sequencing assay; Sanger sequencing assay
• Experiment for Drug Resistance: Immunohistochemical staining assay; Multidrug resistance activity assay; Neutral comet assay
• Mechanism Description: Olaparib-resistant BRCA1m OvCa cells show greater sensitivity to niraparib and rucaparib relative to other PARPis. Niraparib and rucaparib demonstrated greater cytotoxicity and reduced RF speed compared to the other three PARPis, likely due to the higher levels of SSB induction.

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]

• Sensitive Disease: Prostate cancer [ICD-11: 2C82.0]
• Molecule Alteration: Expression; Up-regulation
• 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.
• Ref 2: Poly (ADP-Ribose) Polymerase Inhibitor Olaparib-Resistant BRCA1-Mutant Ovarian Cancer Cells Demonstrate Differential Sensitivity to PARP Inhibitor Rechallenge. Cells. 2024 Nov 7;13(22):1847.