Drug Information

Drug (ID: DG01198) and It's Reported Resistant Information
Name
Rucaparib
Synonyms
RUCAPARIB; 283173-50-2; Rubraca; Rucaparib free base; AG-14447; Rucaparib (free base); UNII-8237F3U7EH; Kinome_3180; 8-Fluoro-1,3,4,5-tetrahydro-2-[4-[(methylamino)methyl]phenyl]-6H-pyrrolo[4,3,2-ef][2]benzazepin-6-one; 8237F3U7EH; 283173-50-2 (free base); 8-Fluoro-2-(4-((methylamino)methyl)phenyl)-1,3,4,5-tetrahydro-6H-azepino(5,4,3-cd)indol-6-one; 8-FLUOR-2-{4-[(METHYLAMINO)METHYL]FENYL}-1,3,4,5-TETRAHYDRO-6HAZEPINO[5,4,3-CD]INDOOL-6-ON; 8-fluoro-2-(4-methylaminomethyl-phenyl)-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one; 6H-Pyrrolo[4,3,2-ef][2]benzazepin-6-one,8-fluoro-1,3,4,5-tetrahydro-2-[4-[(methylamino)methyl]phenyl]-; 8-FLUORO-2-(4-((METHYLAMINO)METHYL)PHENYL)-4,5-DIHYDRO-1H-AZEPINO[5,4,3-CD]INDOL-6(3H)-ONE; C19H18FN3O; 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one; Rucaparib [USAN:INN]; PF 01367338; 8-Fluoro-2-[4-[(methylamino)methyl]phenyl]-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one; RPB; Rucaparib (USAN/INN); Rucaparib(AG-014447); SCHEMBL844585; GTPL7736; CHEMBL1173055; CHEBI:94311; ZINC25958; DTXSID10182563; CHEBI:134689; BCP07633; EX-A2700; BDBM50446130; HY-10617A; NSC756644; s4948; AKOS015898427; AG14447; DB12332; NSC-756644; SB16538; NCGC00263173-01; NCGC00263173-03; NCGC00263173-09; NCGC00263173-13; 6-fluoro-2-[4-(methylaminomethyl)phenyl]-3,10-diazatricyclo[6.4.1.04,13]trideca-1,4,6,8(13)-tetraen-9-one; 6H-Azepino(5,4,3-cd)indol-6-one, 8-fluoro-1,3,4,5-tetrahydro-2-(4-((methylamino)methyl)phenyl)-; 6H-Pyrrolo(4,3,2-ef)(2)benzazepin-6-one, 8-fluoro-1,3,4,5-tetrahydro-2-(4-((methylamino)methyl)phenyl)-; AC-24390; AS-74779; FT-0696622; A14182; C74459; D10079; Rucaparib; AG 014699; PF-01367338; A856084; Q7376558; BRD-K88560311-011-01-4; 6-fluoro-2-[4-(methylaminomethyl)phenyl]-3,10-diazatricyclo[6.4.1.0^{4,13]trideca-1,4,6,8(13)-tetraen-9-one; 6-fluoro-2-{4-[(methylamino)methyl]phenyl}-3,10-diazatricyclo[6.4.1.0 ,(1)(3)]trideca-1,4,6,8(13)-tetraen-9-one; 6H-Pyrrolo[4,3,2-ef][2]benzazepin-6-one,8-fluoro-1,3,4,5-tetrahydro-2-[4-[(methylamino)methyl]phenyl]; 8-fluoro-5-(4-((methylamino)methyl)phenyl)-2,3,4,6-tetrahydro-1H-azepino[5,4,3-cd]indol-1-one
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Indication
In total 2 Indication(s)
Ovarian cancer [ICD-11: 2C73]
Approved
[1]
Ovarian cancer [ICD-11: 2C73]
Approved
[1]
Structure
Target Poly [ADP-ribose] polymerase (PARP) NOUNIPROTAC [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C19H18FN3O
IsoSMILES
CNCC1=CC=C(C=C1)C2=C3CCNC(=O)C4=C3C(=CC(=C4)F)N2
InChI
1S/C19H18FN3O/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/h2-5,8-9,21,23H,6-7,10H2,1H3,(H,22,24)
InChIKey
HMABYWSNWIZPAG-UHFFFAOYSA-N
PubChem CID
9931954
ChEBI ID
CHEBI:94311
TTD Drug ID
D01SHZ
INTEDE ID
DR1449
DrugBank ID
DB12332
Type(s) of Resistant Mechanism of This Drug due to Structure Alteration
  EADR: Epigenetic Alteration of DNA, RNA or Protein
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
Click to Show/Hide the Resistance Disease of This Class
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
  Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: Oxalosuccinate decarboxylase (IDH1) [2]
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Molecule Alteration Missense mutation
p.R132H (c.395G>A)
 Molecule Info 
Wild Type Structure Method: X-ray diffraction Resolution: 1.65  Å
PDB: 6BKX
Mutant Type Structure Method: X-ray diffraction Resolution: 1.88  Å
PDB: 4UMX
   Download The Information of Sequence       Download The Structure File   
RMSD: 3.46
TM score: 0.85834
Amino acid change:
R132H
 : Wild Type Structure
 : Mutant Type Structure
  Mutation site(s) have been marked in red
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60
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A
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140
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160
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170
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G
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G
G
G
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A
A
180
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350
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Click to Show/Hide the Structure
Experimental Note Identified from the Human Clinical Data
In Vitro Model IDH2 cells Ovary Homo sapiens (Human) CVCL_D3DY
IDH1 cells Ovary Homo sapiens (Human) CVCL_D3DY
In Vivo Model Female athymic nu/nu mouse PDX model Mus musculus
Experiment for
Drug Resistance		 Promega assay
Mechanism Description The oncometabolite, 2-hydroxyglutarate, renders IDH1/2 mutant cancer cells deficient in homologous recombination and confers vulnerability to synthetic lethal targeting with PARP inhibitors.
References
Ref 1 Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2) .Nat Commun. 2021 May 3;12(1):2487. doi: 10.1038/s41467-021-22582-6. 10.1038/s41467-021-22582-6
Ref 2 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivitySci Transl Med. 2017 Feb 1;9(375):eaal2463. doi: 10.1126/scitranslmed.aal2463.

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