Drug Information

Drug (ID: DG80006) and It's Reported Resistant Information

• Name: Rucaparib Phosphate
• Synonyms: Rucaparib phosphate|459868-92-9|PF-01367338|AG014699|AG-14699|PF01367338|H3M9955244|RefChem:548076|PARP-1 inhibitor AG014699|PARP1 Inhibitor PF-01367338|AG-014699|AG 014699|Rucaparib (phosphate)|Rucaparib (AG-014699,PF-01367338)|AG-014447|Rucaparib phosphate [USAN]|MFCD17010269|8-Fluoro-2-(4-((methylamino)methyl)phenyl)-4,5-dihydro-1H-azepino[5,4,3-cd]indol-6(3H)-one phosphate|Rucaparib (AG-014699) phosphate|6-fluoro-2-[4-(methylaminomethyl)phenyl]-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-9-one;phosphoric acid|AG 14699|Rucaparib phosphate (USAN)|8-fluoro-2-(4-methylaminomethyl-phenyl)-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one phosphate|8-fluoro-5-(4-((methylamino)methyl)phenyl)-2,3,4,6-tetrahydro-1H-azepino[5,4,3-cd]indol-1-one phosphate|6H-Pyrrolo[4,3,2-ef][2]benzazepin-6-one, 8-fluoro-1,3,4,5-tetrahydro-2-[4-[(methylamino)methyl]phenyl]-, phosphate (1:1)|459868-92-9 (phosphate)|PF 01367338|PF01367338 phosphate|C19H21FN3O5P|UNII-H3M9955244|6H-PYRROLO(4,3,2-EF)(2)BENZAZEPIN-6-ONE, 8-FLUORO-1,3,4,5-TETRAHYDRO-2-(4-((METHYLAMINO)METHYL)PHENYL)-, PHOSPHATE (1:1)|8-Fluoro-1,3,4,5-tetrahydro-2-[4-[(methylamino)methyl]phenyl]-6H-pyrrolo[4,3,2-ef][2]benzazepin-6-one Phosphate; AG 014699; Rucaparib, PF-01367338|Rucaparib (free base)|AG 014699 phosphate|MLS006011099|SCHEMBL844872|Rucaparib (AG-014699,PF-01367338) phosphate|orb1301050|CHEMBL2105733|SCHEMBL29379028|EX-A018|FCCGJTKEKXUBFZ-UHFFFAOYSA-N|DTXSID001365879|GLXC-06310|HMS3426E05|HMS3654A21|HMS5079I09|EBC-11347|RUCAPARIB PHOSPHATE [WHO-DD]|s1098|AKOS025147025|CCG-264819|SB16539|AS-16892|FF141806|HY-10617|SMR004702887|RUCAPARIB PHOSPHATE (AG-014699)|SW219544-1|AG-014699,PF-01367338, Rucaparib|D10157|Rucaparib (AG-014699;PF-01367338)|Q27279598|Rucaparib phosphate (AG-14699, PF-01367338)?|6H-AZEPINO(5,4,3-CD)INDOL-6-ONE, 8-FLUORO-1,3,4,5-TETRAHYDRO-2-(4((METHYLAMINO)METHYL)PHENYL)-, PHOSPHATE (1:1)|8-Fluoro-2-(4-((methylamino)methyl)phenyl)-4,5-dihydro-1H-azepino[5,4,3-cd]indol-6(3H)-onephosphate|8-Fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one phosphate|8-Fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-pyrrolo[4,3,2-ef][2]benzazepin-6-one phosphate (1:1)
• Formula: 3
• IsoSMILES: InChI=1S/C19H18FN3O.H3O4P/c1-21-10-11-2-4-12(5-3-11)18-14-6-7-22-19(24)15-8-13(20)9-16(23-18)17(14)15;1-5(2,3)4/h2-5,8-9,21,23H,6-7,10H2,1H3,(H,22,24);(H3,1,2,3,4)
• InChI: CNCC1=CC=C(C=C1)C2=C3CCNC(=O)C4=C3C(=CC(=C4)F)N2.OP(=O)(O)O
• InChIKey: FCCGJTKEKXUBFZ-UHFFFAOYSA-N
• PubChem CID: 9931953
• DrugBank ID: DB12332

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

Ovarian cancer [ICD-11: 2C73]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-9-1 [1]

• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Balb/c athymic mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Reverse miR library screening revealed that miR-9 reduced the normalized luciferase activity to 60.3% (95% confidence interval [CI] = 52.0% to 68.5%; P < .001). miR-9 bound directly to the 3'-UTR of BRCA1 and downregulated BRCA1 expression in ovarian cancer cells. Treatment with miR-9 agomiR sensitized BRCA1-proficient C13* xenograft tumors to cisplatin and AG014699. In serous ovarian cancer, higher levels of miR-9 were inversely correlated with BRCA1 expression (Spearman rank correlation: R2 = 0.379; P = .003). Patients with higher levels of miR-9 had better chemotherapy response, platinum sensitivity, and longer progression-free survival (PFS) (high vs low miR-9 expression: median PFS = 26.4 months, 95% CI = 13.8 to 39.0 months vs median PFS = 15.4 months, 95% CI = 6.8 to 23.9 months, P = .01).

References

• Ref 1: The dual pathway inhibitor rigosertib is effective in direct patient tumor xenografts of head and neck squamous cell carcinomasMol Cancer Ther. 2013 Oct;12(10):1994-2005. doi: 10.1158/1535-7163.MCT-13-0206. Epub 2013 Jul 19.