Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C19H20N4O.ClH |
| Molecular Weight | 356.849 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.NC(=O)C1=CC=CC2=CN(N=C12)C3=CC=C(C=C3)[C@@H]4CCCNC4
InChI
InChIKey=YXYDNYFWAFBCAN-PFEQFJNWSA-N
InChI=1S/C19H20N4O.ClH/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);1H/t14-;/m1./s1
| Molecular Formula | ClH |
| Molecular Weight | 36.461 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
| Molecular Formula | C19H20N4O |
| Molecular Weight | 320.3883 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
DescriptionSources: http://adisinsight.springer.com/drugs/800028881Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/19873981 | https://www.ncbi.nlm.nih.gov/pubmed/25761096
Sources: http://adisinsight.springer.com/drugs/800028881
Curator's Comment: Description was created based on several sources, including
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23482742 | http://mct.aacrjournals.org/content/14/12_Supplement_2/B168
Curator's Comment: Niraparib is able to penetrate the brain in rodents. No human data available.
Originator
Sources: http://adisinsight.springer.com/drugs/800028881
Curator's Comment: # Merck & Co. Inc.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL3105 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19873981 |
3.8 nM [IC50] | ||
Target ID: CHEMBL5366 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19873981 |
2.1 nM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | ZEJULA Approved UseZEJULA 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 Date2017 |
|||
| Primary | Unknown Approved UseUnknown |
|||
| Primary | Unknown Approved UseUnknown |
|||
| Primary | Unknown Approved UseUnknown |
|||
| Primary | Unknown Approved UseUnknown |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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 |
|
803.7 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29322231 |
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 |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
29016.1 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29322231 |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
50.5 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/29322231 |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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 |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical 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
| Target | Modality | Activity | Metabolite | Clinical 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
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| The Role of PARP Inhibitors in the Treatment of Gynecologic Malignancies. | 2013-10-01 |
|
| Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors. | 2012-11-01 |
|
| 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. | 2009-11-26 |
|
| Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. | 2009-07-09 |
|
| Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. | 2005-04-14 |
|
| Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. | 2005-04-14 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: http://adisinsight.springer.com/drugs/800028881
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19873981
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
Edited
Mon Mar 31 19:04:38 GMT 2025
by
admin
on
Mon Mar 31 19:04:38 GMT 2025
|
| Record UNII |
L4JFC1PHCI
|
| Record Status |
Validated (UNII)
|
| Record Version |
|
-
Download
| Name | Type | Language | ||
|---|---|---|---|---|
|
Common Name | English | ||
|
Preferred Name | English | ||
|
Code | English | ||
|
Systematic Name | English |
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
|
44550597
Created by
admin on Mon Mar 31 19:04:38 GMT 2025 , Edited by admin on Mon Mar 31 19:04:38 GMT 2025
|
PRIMARY | |||
|
DBSALT002076
Created by
admin on Mon Mar 31 19:04:38 GMT 2025 , Edited by admin on Mon Mar 31 19:04:38 GMT 2025
|
PRIMARY | |||
|
1038915-64-8
Created by
admin on Mon Mar 31 19:04:38 GMT 2025 , Edited by admin on Mon Mar 31 19:04:38 GMT 2025
|
PRIMARY | |||
|
DTXSID60146130
Created by
admin on Mon Mar 31 19:04:38 GMT 2025 , Edited by admin on Mon Mar 31 19:04:38 GMT 2025
|
PRIMARY | |||
|
300000053950
Created by
admin on Mon Mar 31 19:04:38 GMT 2025 , Edited by admin on Mon Mar 31 19:04:38 GMT 2025
|
PRIMARY | |||
|
L4JFC1PHCI
Created by
admin on Mon Mar 31 19:04:38 GMT 2025 , Edited by admin on Mon Mar 31 19:04:38 GMT 2025
|
PRIMARY |
| Related Record | Type | Details | ||
|---|---|---|---|---|
|
|
PARENT -> SALT/SOLVATE |
| Related Record | Type | Details | ||
|---|---|---|---|---|
|
|
ACTIVE MOIETY |