Details
Stereochemistry | ACHIRAL |
Molecular Formula | C19H18FN3O |
Molecular Weight | 323.3641 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CNCC1=CC=C(C=C1)C2=C3CCNC(=O)C4=CC(F)=CC(N2)=C34
InChI
InChIKey=HMABYWSNWIZPAG-UHFFFAOYSA-N
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)
Molecular Formula | C19H18FN3O |
Molecular Weight | 323.3641 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionSources: https://www.drugs.com/history/rubraca.html
Sources: https://www.drugs.com/history/rubraca.html
Rucaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for the treatment of advanced mutant BRCA ovarian cancer. Rucaparib is being investigated in clinical trials against prostate cancer, breast cancer and other neoplasms.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3390820 |
0.804 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | RUBRACA Approved UseRUBRACA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated as monotherapy for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more chemotherapies. Select patients for therapy based on an FDA-approved companion diagnostic for RUBRACA. Launch Date2016 |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
629 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29799676 |
300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
RUCAPARIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
5740 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29799676 |
300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
RUCAPARIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
15.2 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29799676 |
300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered: |
RUCAPARIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Doses
Dose | Population | Adverse events |
---|---|---|
840 mg 2 times / day steady, oral Highest studied dose Dose: 840 mg, 2 times / day Route: oral Route: steady Dose: 840 mg, 2 times / day Sources: |
unhealthy, 51 years (range: 21–71 years) n = 3 Health Status: unhealthy Age Group: 51 years (range: 21–71 years) Sex: M+F Population Size: 3 Sources: |
Other AEs: Asthenia, Fatigue... Other AEs: Asthenia (33.3%) Sources: Fatigue (33.3%) Nausea (100%) Vomiting (66.7%) Diarrhea (100%) Decreased appetite (33.3%) Alanine aminotransferase increase (33.3%) Transaminases increased (33.3%) Headache (33.3%) Abdominal pain (33.3%) Dysgeusia (14.3%) Dyspnea (33.3%) |
18 mg/m2 1 times / day multiple, intravenous Dose: 18 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 18 mg/m2, 1 times / day Sources: |
unhealthy, 52 years (range: 23–72 years) n = 33 Health Status: unhealthy Age Group: 52 years (range: 23–72 years) Sex: F Population Size: 33 Sources: |
|
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: |
unhealthy, 62 years (range: 31 - 86 years) n = 377 Health Status: unhealthy Condition: ovarian cancer Age Group: 62 years (range: 31 - 86 years) Sex: F Population Size: 377 Sources: |
Disc. AE: Fatigue, Asthenia... AEs leading to discontinuation/dose reduction: Fatigue (2%) Sources: Asthenia (2%) |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: Page: p. 11-77 |
unhealthy, 62 years (range: 31 - 86 years) n = 378 Health Status: unhealthy Condition: ovarian cancer Age Group: 62 years (range: 31 - 86 years) Sex: F Population Size: 378 Sources: Page: p. 11-77 |
Disc. AE: Intestinal obstruction, Small intestinal obstruction... AEs leading to discontinuation/dose reduction: Intestinal obstruction (1.7%) Sources: Page: p. 11-77Small intestinal obstruction (1.7%) Nausea (1.3%) Abdominal pain (1.1%) Abdominal pain upper (1.1%) |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: Page: p. 11-81 |
unhealthy, 62 years (range: 31 - 86 years) n = 378 Health Status: unhealthy Condition: ovarian cancer Age Group: 62 years (range: 31 - 86 years) Sex: F Population Size: 378 Sources: Page: p. 11-81 |
Disc. AE: Anemia, Fatigue... AEs leading to discontinuation/dose reduction: Anemia (21.2%) Sources: Page: p. 11-81Fatigue (19.8%) Asthenia (19.8%) Hemoglobin decreased (21.2%) Nausea (17.2%) Vomiting (11.4%) Alanine aminotransferase increased (9.8%) Thrombocytopenia (9.8%) Platelet count decreased (6.6%) Neutrophil count decreased (6.3%) Neutropenia (6.3%) Blood creatinine increased (5%) Abdominal pain (4.7%) Abdominal pain upper (4.7%) |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: |
unhealthy, 86 years n = 1 Health Status: unhealthy Age Group: 86 years Sex: M Population Size: 1 Sources: |
Disc. AE: Torsades de pointes... AEs leading to discontinuation/dose reduction: Torsades de pointes (grade 5, 1 patient) Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Diarrhea | 100% | 840 mg 2 times / day steady, oral Highest studied dose Dose: 840 mg, 2 times / day Route: oral Route: steady Dose: 840 mg, 2 times / day Sources: |
unhealthy, 51 years (range: 21–71 years) n = 3 Health Status: unhealthy Age Group: 51 years (range: 21–71 years) Sex: M+F Population Size: 3 Sources: |
Nausea | 100% | 840 mg 2 times / day steady, oral Highest studied dose Dose: 840 mg, 2 times / day Route: oral Route: steady Dose: 840 mg, 2 times / day Sources: |
unhealthy, 51 years (range: 21–71 years) n = 3 Health Status: unhealthy Age Group: 51 years (range: 21–71 years) Sex: M+F Population Size: 3 Sources: |
Dysgeusia | 14.3% | 840 mg 2 times / day steady, oral Highest studied dose Dose: 840 mg, 2 times / day Route: oral Route: steady Dose: 840 mg, 2 times / day Sources: |
unhealthy, 51 years (range: 21–71 years) n = 3 Health Status: unhealthy Age Group: 51 years (range: 21–71 years) Sex: M+F Population Size: 3 Sources: |
Abdominal pain | 33.3% | 840 mg 2 times / day steady, oral Highest studied dose Dose: 840 mg, 2 times / day Route: oral Route: steady Dose: 840 mg, 2 times / day Sources: |
unhealthy, 51 years (range: 21–71 years) n = 3 Health Status: unhealthy Age Group: 51 years (range: 21–71 years) Sex: M+F Population Size: 3 Sources: |
Alanine aminotransferase increase | 33.3% | 840 mg 2 times / day steady, oral Highest studied dose Dose: 840 mg, 2 times / day Route: oral Route: steady Dose: 840 mg, 2 times / day Sources: |
unhealthy, 51 years (range: 21–71 years) n = 3 Health Status: unhealthy Age Group: 51 years (range: 21–71 years) Sex: M+F Population Size: 3 Sources: |
Asthenia | 33.3% | 840 mg 2 times / day steady, oral Highest studied dose Dose: 840 mg, 2 times / day Route: oral Route: steady Dose: 840 mg, 2 times / day Sources: |
unhealthy, 51 years (range: 21–71 years) n = 3 Health Status: unhealthy Age Group: 51 years (range: 21–71 years) Sex: M+F Population Size: 3 Sources: |
Decreased appetite | 33.3% | 840 mg 2 times / day steady, oral Highest studied dose Dose: 840 mg, 2 times / day Route: oral Route: steady Dose: 840 mg, 2 times / day Sources: |
unhealthy, 51 years (range: 21–71 years) n = 3 Health Status: unhealthy Age Group: 51 years (range: 21–71 years) Sex: M+F Population Size: 3 Sources: |
Dyspnea | 33.3% | 840 mg 2 times / day steady, oral Highest studied dose Dose: 840 mg, 2 times / day Route: oral Route: steady Dose: 840 mg, 2 times / day Sources: |
unhealthy, 51 years (range: 21–71 years) n = 3 Health Status: unhealthy Age Group: 51 years (range: 21–71 years) Sex: M+F Population Size: 3 Sources: |
Fatigue | 33.3% | 840 mg 2 times / day steady, oral Highest studied dose Dose: 840 mg, 2 times / day Route: oral Route: steady Dose: 840 mg, 2 times / day Sources: |
unhealthy, 51 years (range: 21–71 years) n = 3 Health Status: unhealthy Age Group: 51 years (range: 21–71 years) Sex: M+F Population Size: 3 Sources: |
Headache | 33.3% | 840 mg 2 times / day steady, oral Highest studied dose Dose: 840 mg, 2 times / day Route: oral Route: steady Dose: 840 mg, 2 times / day Sources: |
unhealthy, 51 years (range: 21–71 years) n = 3 Health Status: unhealthy Age Group: 51 years (range: 21–71 years) Sex: M+F Population Size: 3 Sources: |
Transaminases increased | 33.3% | 840 mg 2 times / day steady, oral Highest studied dose Dose: 840 mg, 2 times / day Route: oral Route: steady Dose: 840 mg, 2 times / day Sources: |
unhealthy, 51 years (range: 21–71 years) n = 3 Health Status: unhealthy Age Group: 51 years (range: 21–71 years) Sex: M+F Population Size: 3 Sources: |
Vomiting | 66.7% | 840 mg 2 times / day steady, oral Highest studied dose Dose: 840 mg, 2 times / day Route: oral Route: steady Dose: 840 mg, 2 times / day Sources: |
unhealthy, 51 years (range: 21–71 years) n = 3 Health Status: unhealthy Age Group: 51 years (range: 21–71 years) Sex: M+F Population Size: 3 Sources: |
Asthenia | 2% Disc. AE |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: |
unhealthy, 62 years (range: 31 - 86 years) n = 377 Health Status: unhealthy Condition: ovarian cancer Age Group: 62 years (range: 31 - 86 years) Sex: F Population Size: 377 Sources: |
Fatigue | 2% Disc. AE |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: |
unhealthy, 62 years (range: 31 - 86 years) n = 377 Health Status: unhealthy Condition: ovarian cancer Age Group: 62 years (range: 31 - 86 years) Sex: F Population Size: 377 Sources: |
Abdominal pain upper | 1.1% Disc. AE |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: Page: p. 11-77 |
unhealthy, 62 years (range: 31 - 86 years) n = 378 Health Status: unhealthy Condition: ovarian cancer Age Group: 62 years (range: 31 - 86 years) Sex: F Population Size: 378 Sources: Page: p. 11-77 |
Abdominal pain | 1.1% Disc. AE |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: Page: p. 11-77 |
unhealthy, 62 years (range: 31 - 86 years) n = 378 Health Status: unhealthy Condition: ovarian cancer Age Group: 62 years (range: 31 - 86 years) Sex: F Population Size: 378 Sources: Page: p. 11-77 |
Nausea | 1.3% Disc. AE |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: Page: p. 11-77 |
unhealthy, 62 years (range: 31 - 86 years) n = 378 Health Status: unhealthy Condition: ovarian cancer Age Group: 62 years (range: 31 - 86 years) Sex: F Population Size: 378 Sources: Page: p. 11-77 |
Intestinal obstruction | 1.7% Disc. AE |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: Page: p. 11-77 |
unhealthy, 62 years (range: 31 - 86 years) n = 378 Health Status: unhealthy Condition: ovarian cancer Age Group: 62 years (range: 31 - 86 years) Sex: F Population Size: 378 Sources: Page: p. 11-77 |
Small intestinal obstruction | 1.7% Disc. AE |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: Page: p. 11-77 |
unhealthy, 62 years (range: 31 - 86 years) n = 378 Health Status: unhealthy Condition: ovarian cancer Age Group: 62 years (range: 31 - 86 years) Sex: F Population Size: 378 Sources: Page: p. 11-77 |
Vomiting | 11.4% Disc. AE |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: Page: p. 11-81 |
unhealthy, 62 years (range: 31 - 86 years) n = 378 Health Status: unhealthy Condition: ovarian cancer Age Group: 62 years (range: 31 - 86 years) Sex: F Population Size: 378 Sources: Page: p. 11-81 |
Nausea | 17.2% Disc. AE |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: Page: p. 11-81 |
unhealthy, 62 years (range: 31 - 86 years) n = 378 Health Status: unhealthy Condition: ovarian cancer Age Group: 62 years (range: 31 - 86 years) Sex: F Population Size: 378 Sources: Page: p. 11-81 |
Asthenia | 19.8% Disc. AE |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: Page: p. 11-81 |
unhealthy, 62 years (range: 31 - 86 years) n = 378 Health Status: unhealthy Condition: ovarian cancer Age Group: 62 years (range: 31 - 86 years) Sex: F Population Size: 378 Sources: Page: p. 11-81 |
Fatigue | 19.8% Disc. AE |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: Page: p. 11-81 |
unhealthy, 62 years (range: 31 - 86 years) n = 378 Health Status: unhealthy Condition: ovarian cancer Age Group: 62 years (range: 31 - 86 years) Sex: F Population Size: 378 Sources: Page: p. 11-81 |
Anemia | 21.2% Disc. AE |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: Page: p. 11-81 |
unhealthy, 62 years (range: 31 - 86 years) n = 378 Health Status: unhealthy Condition: ovarian cancer Age Group: 62 years (range: 31 - 86 years) Sex: F Population Size: 378 Sources: Page: p. 11-81 |
Hemoglobin decreased | 21.2% Disc. AE |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: Page: p. 11-81 |
unhealthy, 62 years (range: 31 - 86 years) n = 378 Health Status: unhealthy Condition: ovarian cancer Age Group: 62 years (range: 31 - 86 years) Sex: F Population Size: 378 Sources: Page: p. 11-81 |
Abdominal pain upper | 4.7% Disc. AE |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: Page: p. 11-81 |
unhealthy, 62 years (range: 31 - 86 years) n = 378 Health Status: unhealthy Condition: ovarian cancer Age Group: 62 years (range: 31 - 86 years) Sex: F Population Size: 378 Sources: Page: p. 11-81 |
Abdominal pain | 4.7% Disc. AE |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: Page: p. 11-81 |
unhealthy, 62 years (range: 31 - 86 years) n = 378 Health Status: unhealthy Condition: ovarian cancer Age Group: 62 years (range: 31 - 86 years) Sex: F Population Size: 378 Sources: Page: p. 11-81 |
Blood creatinine increased | 5% Disc. AE |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: Page: p. 11-81 |
unhealthy, 62 years (range: 31 - 86 years) n = 378 Health Status: unhealthy Condition: ovarian cancer Age Group: 62 years (range: 31 - 86 years) Sex: F Population Size: 378 Sources: Page: p. 11-81 |
Neutropenia | 6.3% Disc. AE |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: Page: p. 11-81 |
unhealthy, 62 years (range: 31 - 86 years) n = 378 Health Status: unhealthy Condition: ovarian cancer Age Group: 62 years (range: 31 - 86 years) Sex: F Population Size: 378 Sources: Page: p. 11-81 |
Neutrophil count decreased | 6.3% Disc. AE |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: Page: p. 11-81 |
unhealthy, 62 years (range: 31 - 86 years) n = 378 Health Status: unhealthy Condition: ovarian cancer Age Group: 62 years (range: 31 - 86 years) Sex: F Population Size: 378 Sources: Page: p. 11-81 |
Platelet count decreased | 6.6% Disc. AE |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: Page: p. 11-81 |
unhealthy, 62 years (range: 31 - 86 years) n = 378 Health Status: unhealthy Condition: ovarian cancer Age Group: 62 years (range: 31 - 86 years) Sex: F Population Size: 378 Sources: Page: p. 11-81 |
Alanine aminotransferase increased | 9.8% Disc. AE |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: Page: p. 11-81 |
unhealthy, 62 years (range: 31 - 86 years) n = 378 Health Status: unhealthy Condition: ovarian cancer Age Group: 62 years (range: 31 - 86 years) Sex: F Population Size: 378 Sources: Page: p. 11-81 |
Thrombocytopenia | 9.8% Disc. AE |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: Page: p. 11-81 |
unhealthy, 62 years (range: 31 - 86 years) n = 378 Health Status: unhealthy Condition: ovarian cancer Age Group: 62 years (range: 31 - 86 years) Sex: F Population Size: 378 Sources: Page: p. 11-81 |
Torsades de pointes | grade 5, 1 patient Disc. AE |
600 mg 2 times / day steady, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: steady Dose: 600 mg, 2 times / day Sources: |
unhealthy, 86 years n = 1 Health Status: unhealthy Age Group: 86 years Sex: M Population Size: 1 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no [Inhibition 300 uM] | ||||
no [Inhibition 300 uM] | ||||
no [Inhibition 300 uM] | ||||
no [Inhibition 300 uM] | ||||
Page: 15.0 |
no | |||
Page: 15.0 |
no | |||
Page: 15.0 |
no | |||
Page: 15.0 |
no | |||
Page: 15.0 |
no | |||
strong [IC50 0.19 uM] | ||||
strong [IC50 0.63 uM] | ||||
Page: 14.0 |
yes [IC50 12.9 uM] | yes (co-administration study) Comment: warfarin AUC increased 1.49-fold Page: 14.0 |
||
yes [IC50 169 uM] | weak (co-administration study) Comment: digoxin AUC increased 1.2-fold |
|||
Page: 14.0 |
yes [IC50 3.55 uM] | yes (co-administration study) Comment: caffeine AUC increased 2.55-fold Page: 14.0 |
||
yes [IC50 31 uM] | ||||
yes [IC50 4.3 uM] | ||||
yes [IC50 41.6 uM] | ||||
Page: 14.0 |
yes [IC50 5.42 uM] | yes (co-administration study) Comment: omeprazole AUC increased 1.55-fold Page: 14.0 |
||
yes [IC50 55 uM] | ||||
Page: 15.0 |
yes | |||
Page: 15.0 |
yes | |||
Page: 15.0 |
yes | |||
Page: 15.0 |
yes | |||
Page: 15.0 |
yes | |||
Page: 14.0 |
yes | yes (co-administration study) Comment: midazolam AUC increased 1.38-fold Page: 14.0 |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 15.0 |
no | |||
Page: 15.0 |
no | |||
Page: 15.0 |
no | |||
Page: 15.0 |
no | |||
Page: 15.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/209115Orig1s000MultiDisciplineR.pdf Page: 56, 59, 65 |
no | no (pharmacogenomic study) Comment: based on population PK analyses there appeared to be no significant difference in steady-state exposure of rucaparib among CYP2D6 phenotypes Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/209115Orig1s000MultiDisciplineR.pdf Page: 56, 59, 65 |
||
Page: 15.0 |
yes | |||
Page: 1.0 |
yes | |||
Page: 1.0 |
yes | |||
Page: 1.0 |
yes | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/209115Orig1s000MultiDisciplineR.pdf Page: 57.0 |
yes | |||
Page: 1.0 |
yes | no (pharmacogenomic study) Comment: based on population PK analyses there appeared to be no significant difference in steady-state exposure of rucaparib among CYP1A2 phenotypes Page: 1.0 |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/209115Orig1s000MultiDisciplineR.pdf Page: 38.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Potentiation of temozolomide and topotecan growth inhibition and cytotoxicity by novel poly(adenosine diphosphoribose) polymerase inhibitors in a panel of human tumor cell lines. | 2000 Jul |
|
Anticancer chemosensitization and radiosensitization by the novel poly(ADP-ribose) polymerase-1 inhibitor AG14361. | 2004 Jan 7 |
|
Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial. | 2007 Mar |
Sample Use Guides
Recommended dose is 600 mg orally twice daily with or without food.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21183737
Exponentially proliferating cells were plated into six-well plates and incubated for 48 hours to allow cells to reach their optimum proliferation rate. AG014699 at 0, 0.1, 1.0, 10.0, 30.0, 50.0, or 100 μM in 1% dimethyl sulfoxide was added to the wells and incubated for 24 hours. Control cells received no AG014699 but were treated with medium containing 1% dimethyl sulfoxide for 24 hours. Cells were harvested and cultured in drug-free medium in 90-mm Petri dishes for up to 21 days, depending on the proliferation rate of the individual cell line. Colonies were fixed in methanol and acetic acid (3:1 vol/vol), stained with methyl violet 10B, and counted with an automated colony counter (Oxford Optronix, Oxford, UK). Data are expressed as the percentage of colonies in AG014699-treated cultures compared with that in control cultures. AG014699 (≤10 μM) was cytotoxic to cells with mutated BRCA1/2 or XRCC3 and to UACC3199 cells with epigenetically silenced BRCA1 but not to cells without BRCA1/2 or XRCC3 mutations or that were heterozygous for BRCA2 mutation
Substance Class |
Chemical
Created
by
admin
on
Edited
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by
admin
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Record UNII |
8237F3U7EH
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Record Status |
Validated (UNII)
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Record Version |
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C62554
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WHO-ATC |
L01XX55
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NDF-RT |
N0000191623
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FDA ORPHAN DRUG |
374712
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EU-Orphan Drug |
EU/3/12/1049
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8237F3U7EH
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SUB74859
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DB12332
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9931954
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5203
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134689
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CHEMBL1173055
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1862579
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283173-50-2
Created by
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XX-94
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9471
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Rucaparib
Created by
admin on Sat Dec 16 00:25:47 GMT 2023 , Edited by admin on Sat Dec 16 00:25:47 GMT 2023
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C137800
Created by
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DTXSID10182563
Created by
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m11980
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8237F3U7EH
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RUCAPARIB
Created by
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100000136799
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N0000191622
Created by
admin on Sat Dec 16 00:25:47 GMT 2023 , Edited by admin on Sat Dec 16 00:25:47 GMT 2023
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PRIMARY | Poly(ADP-Ribose) Polymerase Inhibitors [MoA] |
Related Record | Type | Details | ||
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TRANSPORTER -> SUBSTRATE | |||
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TARGET -> INHIBITOR |
IC50
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TRANSPORTER -> INHIBITOR |
MODERATE
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SALT/SOLVATE -> PARENT | |||
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METABOLIC ENZYME -> INHIBITOR |
REVERSIBLE
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TRANSPORTER -> SUBSTRATE | |||
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METABOLIC ENZYME -> SUBSTRATE |
MAJOR
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TRANSPORTER -> INHIBITOR | |||
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METABOLIC ENZYME -> SUBSTRATE |
In vitro, rucaparib was metabolized primarily by CYP2D6 and to a lesser extent by CYP1A2 and CYP3A4.
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METABOLIC ENZYME -> INHIBITOR |
REVERSIBLE
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METABOLIC ENZYME -> INHIBITOR | |||
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TARGET -> INHIBITOR |
IC50
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BINDER->LIGAND |
BINDING
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METABOLIC ENZYME -> INHIBITOR |
REVERSIBLE
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SALT/SOLVATE -> PARENT | |||
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METABOLIC ENZYME -> SUBSTRATE |
In vitro, rucaparib was metabolized primarily by CYP2D6 and to a lesser extent by CYP1A2 and CYP3A4.
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METABOLIC ENZYME -> INHIBITOR |
REVERSIBLE
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METABOLIC ENZYME -> INDUCER |
Related Record | Type | Details | ||
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METABOLITE -> PARENT |
MAJOR
PLASMA
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METABOLITE -> PARENT | |||
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METABOLITE -> PARENT |
MAJOR
PLASMA
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METABOLITE -> PARENT |
MINOR
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METABOLITE -> PARENT |
Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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Tmax | PHARMACOKINETIC |
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Volume of Distribution | PHARMACOKINETIC |
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blood-to-plasma ratio | PHARMACOKINETIC |
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