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Details

Stereochemistry ABSOLUTE
Molecular Formula C19H20N4O
Molecular Weight 320.389
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NIRAPARIB

SMILES

c1cc2cn(-c3ccc(cc3)[C@]4([H])CCCNC4)nc2c(c1)C(=N)O

InChI

InChIKey=PCHKPVIQAHNQLW-CQSZACIVSA-N
InChI=1S/C19H20N4O/c20-19(24)17-5-1-3-15-12-23(22-18(15)17)16-8-6-13(7-9-16)14-4-2-10-21-11-14/h1,3,5-9,12,14,21H,2,4,10-11H2,(H2,20,24)/t14-/m1/s1

HIDE SMILES / InChI

Molecular Formula C19H20N4O
Molecular Weight 320.389
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: https://www.ncbi.nlm.nih.gov/pubmed/19873981 | https://www.ncbi.nlm.nih.gov/pubmed/25761096

Niraparib (MK-4827) displays excellent PARP 1 and 2 inhibition. Inhibition of PARP in the context of defects in other DNA repair mechanisms provide a tumor specific way to kill cancer cells. Niraparib is in development with TESARO, under licence from Merck & Co, for the treatment of cancers (ovarian, fallopian tube and peritoneal cancer, breast cancer, prostate cancer and Ewing's sarcoma). Niraparib was characterized in a number of preclinical models before moving to phase I clinical trials, where it showed excellent human pharmacokinetics suitable for once a day oral dosing, achieved its pharmacodynamic target for PARP inhibition, and had promising activity in cancer patients. It is currently being tested in phase 3 clinical trials as maintenance therapy in ovarian cancer and as a treatment for breast cancer.

CNS Activity

Curator's Comment:: Niraparib is able to penetrate the brain in rodents. No human data available.

Originator

Curator's Comment:: # Merck & Co. Inc.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
3.79999999999999982 nM [IC50]
2.10000000000000009 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ZEJULA

Approved Use

ZEJULA is a poly(ADP-ribose) polymerase (PARP) inhibitor indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

Launch Date

1490486400000
Primary
Primary
Primary
Primary
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
803.7 ng/mL
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NIRAPARIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
804 ng/mL
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NIRAPARIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
29016.1 ng × h/mL
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NIRAPARIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
50.5 h
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NIRAPARIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
17%
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NIRAPARIB plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
400 mg 1 times / day steady, oral
Highest studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 59 years (range: 39–75 years)
Health Status: unhealthy
Age Group: 59 years (range: 39–75 years)
Sex: M+F
Sources:
DLT: Thrombocytopenia...
Other AEs: Neutropenia, Neutropenia...
Dose limiting toxicities:
Thrombocytopenia (grade 4, 2 patients)
Other AEs:
Neutropenia (grade 1-2, 3 patients)
Neutropenia (grade 3, 1 patient)
Lymphopenia (grade 3, 1 patient)
Nausea (grade 1-2, 3 patients)
Vomiting (grade 1-2, 3 patients)
Constipation (grade 1-2, 2 patients)
Anorexia (grade 1-2, 2 patients)
Fatigue (grade 1-2, 4 patients)
Insomnia (grade 1-2, 2 patients)
Sources:
30 mg 1 times / day steady, oral
Dose: 30 mg, 1 times / day
Route: oral
Route: steady
Dose: 30 mg, 1 times / day
Sources:
unhealthy, 59 years (range: 39–75 years)
Health Status: unhealthy
Age Group: 59 years (range: 39–75 years)
Sex: M+F
Sources:
DLT: Fatigue...
Dose limiting toxicities:
Fatigue (grade 3, 1 patient)
Sources:
60 mg 1 times / day steady, oral
Dose: 60 mg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg, 1 times / day
Sources:
unhealthy, 59 years (range: 39–75 years)
Health Status: unhealthy
Age Group: 59 years (range: 39–75 years)
Sex: M+F
Sources:
DLT: Pneumonitis...
Dose limiting toxicities:
Pneumonitis (grade 3, 1 patient)
Sources:
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Disc. AE: Thrombocytopenia, Anemia...
Other AEs: Thrombocytopenia, Thrombocytopenia...
AEs leading to
discontinuation/dose reduction:
Thrombocytopenia (3%)
Anemia (1%)
Neutropenia (2%)
Hypertension (<1%)
Myelodysplastic syndrome (grade 5, 1 patient)
Other AEs:
Thrombocytopenia (grade 1-2, 32%)
Thrombocytopenia (grade 3-4, 29%)
Anemia (grade 1-2, 25%)
Anemia (grade 3-4, 25%)
Neutropenia (grade 1-2, 10%)
Neutropenia (grade 3-4, 20%)
Leukopenia (grade 1-2, 12%)
Leukopenia (grade 3-4, 5%)
Palpitations (grade 1-2, 10%)
Nausea (grade 1-2, 71%)
Nausea (grade 3-4, 3%)
Abdominal distension (grade 1-2, 31%)
Abdominal distension (grade 3-4, 2%)
Vomiting (grade 1-2, 32%)
Vomiting (grade 3-4, 2%)
Constipation (grade 1-2, 39.2%)
Constipation (grade 3-4, 0.8%)
Mucositis (grade 1-2, 19.5%)
Mucositis (grade 3-4, 0.5%)
Stomatitis (grade 1-2, 19.5%)
Stomatitis (grade 3-4, 0.5%)
Diarrhea (grade 1-2, 19.7%)
Diarrhea (grade 3-4, 0.3%)
Dyspepsia (grade 1-2, 18%)
Dry mouth (grade 1-2, 9.7%)
Dry mouth (grade 3-4, 0.3%)
Fatigue (grade 1-2, 49%)
Fatigue (grade 1-2, 49%)
Asthenia (grade 3-4, 8%)
Asthenia (grade 3-4, 8%)
Decreased appetite (grade 1-2, 24.7%)
Decreased appetite (grade 3-4, 0.3%)
Urinary tract infection (grade 1-2, 12.2%)
Urinary tract infection (grade 3-4, 0.8%)
Aspartate aminotransferase increased (grade 1-2, 6%)
Aspartate aminotransferase increased (grade 3-4, 4%)
Alanine aminotransferase increase (grade 1-2, 6%)
Alanine aminotransferase increase (grade 3-4, 4%)
Myalgia (grade 1-2, 18.2%)
Myalgia (grade 3-4, 0.8%)
Back pain (grade 1-2, 17.2%)
Back pain (grade 3-4, 0.8%)
Arthralgia (grade 1-2, 12.7%)
Arthralgia (grade 3-4, 0.3%)
Headache (grade 1-2, 25.7%)
Headache (grade 3-4, 0.3%)
Dizziness (grade 1-2, 18%)
Dysgeusia (grade 1-2, 10%)
Insomnia (grade 1-2, 26.7%)
Insomnia (grade 3-4, 0.3%)
Anxiety (grade 1-2, 10.7%)
Anxiety (grade 3-4, 0.3%)
Nasopharyngitis (grade 1-2, 23%)
Dyspnea (grade 1-2, 19%)
Dyspnea (grade 3-4, 1%)
Cough (grade 1-2, 16%)
Rash (grade 1-2, 20.5%)
Rash (grade 3-4, 0.5%)
Hypertension (grade 1-2, 11%)
Hypertension (grade 3-4, 9%)
Decreased hemoglobin (grade 1-2, 60%)
Decreased hemoglobin (grade 3-4, 25%)
Platelet count decreased (grade 1-2, 37%)
Platelet count decreased (grade 3-4, 35%)
WBC decreased (grade 1-2, 59%)
WBC decreased (grade 3-4, 7%)
Absolute neutrophil count decreased (grade 1-2, 32%)
Absolute neutrophil count decreased (grade 3-4, 21%)
Myelodysplastic syndrome (all grades, 1.4%)
Tachycardia (1-10)
Peripheral edema (1-10)
Hypokalemia (1-10)
Bronchitis (1-10)
Conjunctivitis (1-10)
Gamma-glutamyltransferase increased (1-10)
Blood creatinine increased (1-10)
Blood alkaline phosphatase increased (1-10)
Weight decreased (1-10)
Depression (1-10)
Epistaxis (1-10)
Sources:
AEs

AEs

AESignificanceDosePopulation
Anorexia grade 1-2, 2 patients
400 mg 1 times / day steady, oral
Highest studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 59 years (range: 39–75 years)
Health Status: unhealthy
Age Group: 59 years (range: 39–75 years)
Sex: M+F
Sources:
Constipation grade 1-2, 2 patients
400 mg 1 times / day steady, oral
Highest studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 59 years (range: 39–75 years)
Health Status: unhealthy
Age Group: 59 years (range: 39–75 years)
Sex: M+F
Sources:
Insomnia grade 1-2, 2 patients
400 mg 1 times / day steady, oral
Highest studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 59 years (range: 39–75 years)
Health Status: unhealthy
Age Group: 59 years (range: 39–75 years)
Sex: M+F
Sources:
Nausea grade 1-2, 3 patients
400 mg 1 times / day steady, oral
Highest studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 59 years (range: 39–75 years)
Health Status: unhealthy
Age Group: 59 years (range: 39–75 years)
Sex: M+F
Sources:
Neutropenia grade 1-2, 3 patients
400 mg 1 times / day steady, oral
Highest studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 59 years (range: 39–75 years)
Health Status: unhealthy
Age Group: 59 years (range: 39–75 years)
Sex: M+F
Sources:
Vomiting grade 1-2, 3 patients
400 mg 1 times / day steady, oral
Highest studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 59 years (range: 39–75 years)
Health Status: unhealthy
Age Group: 59 years (range: 39–75 years)
Sex: M+F
Sources:
Fatigue grade 1-2, 4 patients
400 mg 1 times / day steady, oral
Highest studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 59 years (range: 39–75 years)
Health Status: unhealthy
Age Group: 59 years (range: 39–75 years)
Sex: M+F
Sources:
Lymphopenia grade 3, 1 patient
400 mg 1 times / day steady, oral
Highest studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 59 years (range: 39–75 years)
Health Status: unhealthy
Age Group: 59 years (range: 39–75 years)
Sex: M+F
Sources:
Neutropenia grade 3, 1 patient
400 mg 1 times / day steady, oral
Highest studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 59 years (range: 39–75 years)
Health Status: unhealthy
Age Group: 59 years (range: 39–75 years)
Sex: M+F
Sources:
Thrombocytopenia grade 4, 2 patients
DLT, Disc. AE
400 mg 1 times / day steady, oral
Highest studied dose
Dose: 400 mg, 1 times / day
Route: oral
Route: steady
Dose: 400 mg, 1 times / day
Sources:
unhealthy, 59 years (range: 39–75 years)
Health Status: unhealthy
Age Group: 59 years (range: 39–75 years)
Sex: M+F
Sources:
Fatigue grade 3, 1 patient
DLT
30 mg 1 times / day steady, oral
Dose: 30 mg, 1 times / day
Route: oral
Route: steady
Dose: 30 mg, 1 times / day
Sources:
unhealthy, 59 years (range: 39–75 years)
Health Status: unhealthy
Age Group: 59 years (range: 39–75 years)
Sex: M+F
Sources:
Pneumonitis grade 3, 1 patient
DLT
60 mg 1 times / day steady, oral
Dose: 60 mg, 1 times / day
Route: oral
Route: steady
Dose: 60 mg, 1 times / day
Sources:
unhealthy, 59 years (range: 39–75 years)
Health Status: unhealthy
Age Group: 59 years (range: 39–75 years)
Sex: M+F
Sources:
Anemia 1%
Disc. AE
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Blood alkaline phosphatase increased 1-10
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Blood creatinine increased 1-10
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Bronchitis 1-10
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Conjunctivitis 1-10
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Depression 1-10
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Epistaxis 1-10
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Gamma-glutamyltransferase increased 1-10
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Hypokalemia 1-10
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Peripheral edema 1-10
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Tachycardia 1-10
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Weight decreased 1-10
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Neutropenia 2%
Disc. AE
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Thrombocytopenia 3%
Disc. AE
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Hypertension <1%
Disc. AE
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Myelodysplastic syndrome all grades, 1.4%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Dysgeusia grade 1-2, 10%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Neutropenia grade 1-2, 10%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Palpitations grade 1-2, 10%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Anxiety grade 1-2, 10.7%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Hypertension grade 1-2, 11%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Leukopenia grade 1-2, 12%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Urinary tract infection grade 1-2, 12.2%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Arthralgia grade 1-2, 12.7%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Cough grade 1-2, 16%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Back pain grade 1-2, 17.2%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Dizziness grade 1-2, 18%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Dyspepsia grade 1-2, 18%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Myalgia grade 1-2, 18.2%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Dyspnea grade 1-2, 19%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Mucositis grade 1-2, 19.5%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Stomatitis grade 1-2, 19.5%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Diarrhea grade 1-2, 19.7%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Rash grade 1-2, 20.5%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Nasopharyngitis grade 1-2, 23%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Decreased appetite grade 1-2, 24.7%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Anemia grade 1-2, 25%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Headache grade 1-2, 25.7%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Insomnia grade 1-2, 26.7%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Abdominal distension grade 1-2, 31%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Absolute neutrophil count decreased grade 1-2, 32%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Thrombocytopenia grade 1-2, 32%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Vomiting grade 1-2, 32%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Platelet count decreased grade 1-2, 37%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Constipation grade 1-2, 39.2%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Fatigue grade 1-2, 49%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Fatigue grade 1-2, 49%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
WBC decreased grade 1-2, 59%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Alanine aminotransferase increase grade 1-2, 6%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Aspartate aminotransferase increased grade 1-2, 6%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Decreased hemoglobin grade 1-2, 60%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Nausea grade 1-2, 71%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Dry mouth grade 1-2, 9.7%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Anxiety grade 3-4, 0.3%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Arthralgia grade 3-4, 0.3%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Decreased appetite grade 3-4, 0.3%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Diarrhea grade 3-4, 0.3%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Dry mouth grade 3-4, 0.3%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Headache grade 3-4, 0.3%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Insomnia grade 3-4, 0.3%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Mucositis grade 3-4, 0.5%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Rash grade 3-4, 0.5%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Stomatitis grade 3-4, 0.5%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Back pain grade 3-4, 0.8%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Constipation grade 3-4, 0.8%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Myalgia grade 3-4, 0.8%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Urinary tract infection grade 3-4, 0.8%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Dyspnea grade 3-4, 1%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Abdominal distension grade 3-4, 2%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Vomiting grade 3-4, 2%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Neutropenia grade 3-4, 20%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Absolute neutrophil count decreased grade 3-4, 21%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Anemia grade 3-4, 25%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Decreased hemoglobin grade 3-4, 25%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Thrombocytopenia grade 3-4, 29%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Nausea grade 3-4, 3%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Platelet count decreased grade 3-4, 35%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Alanine aminotransferase increase grade 3-4, 4%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Aspartate aminotransferase increased grade 3-4, 4%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Leukopenia grade 3-4, 5%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
WBC decreased grade 3-4, 7%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Asthenia grade 3-4, 8%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Asthenia grade 3-4, 8%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Hypertension grade 3-4, 9%
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
Myelodysplastic syndrome grade 5, 1 patient
Disc. AE
300 mg 1 times / day steady, oral
Recommended|MTD
Dose: 300 mg, 1 times / day
Route: oral
Route: steady
Dose: 300 mg, 1 times / day
Sources:
unhealthy
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
weak [Inhibition 161 uM]
weak
weak
yes [IC50 1.21 uM]
yes [Inhibition 0.18 uM]
yes [Inhibition <0.14 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
yes
yes
yes
yes
yes
yes
yes
yes
Tox targets

Tox targets

Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase.
2005 Apr 14
Discovery of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors.
2009 Nov 26
Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors.
2012 Nov 1
The Role of PARP Inhibitors in the Treatment of Gynecologic Malignancies.
2013 Oct 1
Patents

Sample Use Guides

Niraparib (PO, 110-210 mg) successfully inhibited poly(ADP-ribose) polymerase (PARP) during a phase I trial in patients with BRCA-deficient or sporadic cancers associated with homologous recombination repair defects. Niraparib (PO, 30-210 mg) was well tolerated during a phase I trial in patients with BRCA-deficient or sporadic cancers associated with homologous recombination repair defects. Maximum tolerated dose (MTD) of niraparib in patients with advanced solid tumours was 300 mg.
Route of Administration: Oral
Niraparib (MK-4827) inhibited proliferation of cancer cells with mutant BRCA-1 and BRCA-2 with CC(50) in the 10-100 nM range.
Substance Class Chemical
Created
by admin
on Sat Jun 26 06:04:24 UTC 2021
Edited
by admin
on Sat Jun 26 06:04:24 UTC 2021
Record UNII
HMC2H89N35
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
NIRAPARIB
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
JNJ-64091742
Code English
NIRAPARIB [MI]
Common Name English
MK-4827
Code English
2-(4-((3S)-PIPERIDIN-3-YL)PHENYL)-2H-INDAZOLE-7-CARBOXAMIDE
Systematic Name English
ZL-2306
Code English
NIRAPARIB [WHO-DD]
Common Name English
NIRAPARIB [USAN]
Common Name English
2H-INDAZOLE-7-CARBOXAMIDE, 2-(4-(3S)-3-PIPERIDINYLPHENYL)-
Systematic Name English
MK4827
Code English
NIRAPARIB [INN]
Common Name English
Classification Tree Code System Code
NDF-RT N0000191623
Created by admin on Sat Jun 26 06:04:24 UTC 2021 , Edited by admin on Sat Jun 26 06:04:24 UTC 2021
FDA ORPHAN DRUG 306510
Created by admin on Sat Jun 26 06:04:24 UTC 2021 , Edited by admin on Sat Jun 26 06:04:24 UTC 2021
WHO-ATC L01XX54
Created by admin on Sat Jun 26 06:04:24 UTC 2021 , Edited by admin on Sat Jun 26 06:04:24 UTC 2021
NCI_THESAURUS C62554
Created by admin on Sat Jun 26 06:04:24 UTC 2021 , Edited by admin on Sat Jun 26 06:04:24 UTC 2021
Code System Code Type Description
MERCK INDEX
M11995
Created by admin on Sat Jun 26 06:04:24 UTC 2021 , Edited by admin on Sat Jun 26 06:04:24 UTC 2021
PRIMARY
EPA CompTox
1038915-60-4
Created by admin on Sat Jun 26 06:04:24 UTC 2021 , Edited by admin on Sat Jun 26 06:04:24 UTC 2021
PRIMARY
NCI_THESAURUS
C80059
Created by admin on Sat Jun 26 06:04:24 UTC 2021 , Edited by admin on Sat Jun 26 06:04:24 UTC 2021
PRIMARY
WIKIPEDIA
NIRAPARIB
Created by admin on Sat Jun 26 06:04:24 UTC 2021 , Edited by admin on Sat Jun 26 06:04:24 UTC 2021
PRIMARY
FDA UNII
HMC2H89N35
Created by admin on Sat Jun 26 06:04:24 UTC 2021 , Edited by admin on Sat Jun 26 06:04:24 UTC 2021
PRIMARY
PUBCHEM
24958200
Created by admin on Sat Jun 26 06:04:24 UTC 2021 , Edited by admin on Sat Jun 26 06:04:24 UTC 2021
PRIMARY
ChEMBL
CHEMBL1094636
Created by admin on Sat Jun 26 06:04:24 UTC 2021 , Edited by admin on Sat Jun 26 06:04:24 UTC 2021
PRIMARY
DRUG CENTRAL
5222
Created by admin on Sat Jun 26 06:04:24 UTC 2021 , Edited by admin on Sat Jun 26 06:04:24 UTC 2021
PRIMARY
DRUG BANK
DB11793
Created by admin on Sat Jun 26 06:04:24 UTC 2021 , Edited by admin on Sat Jun 26 06:04:24 UTC 2021
PRIMARY
CAS
1038915-60-4
Created by admin on Sat Jun 26 06:04:24 UTC 2021 , Edited by admin on Sat Jun 26 06:04:24 UTC 2021
PRIMARY
RXCUI
1918231
Created by admin on Sat Jun 26 06:04:24 UTC 2021 , Edited by admin on Sat Jun 26 06:04:24 UTC 2021
PRIMARY
EVMPD
SUB177208
Created by admin on Sat Jun 26 06:04:24 UTC 2021 , Edited by admin on Sat Jun 26 06:04:24 UTC 2021
PRIMARY
LACTMED
Niraparib
Created by admin on Sat Jun 26 06:04:24 UTC 2021 , Edited by admin on Sat Jun 26 06:04:24 UTC 2021
PRIMARY
INN
9526
Created by admin on Sat Jun 26 06:04:24 UTC 2021 , Edited by admin on Sat Jun 26 06:04:24 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
OFF-TARGET->INHIBITOR
BINDING
IC50
BINDER->LIGAND
BINDING
TRANSPORTER -> SUBSTRATE
Niraparib is a substrate of P-gp and BCRP in vitro.
TRANSPORTER -> SUBSTRATE
Niraparib is a substrate of P-gp and BCRP in vitro.
EXCRETED UNCHANGED
AMOUNT EXCRETED
URINE
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
TARGET -> INHIBITOR
IC50
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
EXCRETED UNCHANGED
AMOUNT EXCRETED
FECAL
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

Volume of Distribution PHARMACOKINETIC