Niraparib tosylate monohydrate

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H20N4O.C7H8O3S.H2O
Molecular Weight	510.605
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of Niraparib tosylate monohydrate

Structure Search

SMILES

O.CC1=CC=C(C=C1)S(O)(=O)=O.NC(=O)C2=CC=CC3=CN(N=C23)C4=CC=C(C=C4)[C@@H]5CCCNC5

InChI

InChIKey=ACNPUCQQZDAPJH-FMOMHUKBSA-N

InChI=1S/C19H20N4O.C7H8O3S.H2O/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;1-6-2-4-7(5-3-6)11(8,9)10;/h1,3,5-9,12,14,21H,2,4,10-11H2,(H2,20,24);2-5H,1H3,(H,8,9,10);1H2/t14-;;/m1../s1

HIDE SMILES / InChI

Molecular Formula	C7H8O3S
Molecular Weight	172.202
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	H2O
Molecular Weight	18.0153
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

Description
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Poly [ADP-ribose] polymerase-1 23 Target ID: CHEMBL3105 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19873981	Inhibitor 8297		3.8 nM [IC50]
Poly [ADP-ribose] polymerase 2 16 Target ID: CHEMBL5366 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19873981	Inhibitor 8297		2.1 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
epithelial ovarian cancer 4 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208447lbl.pdf	Primary	Approved 8429	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 2017
Ovarian cancer 157 Sources: http://adisinsight.springer.com/drugs/800028881	Primary	Phase III 656	Unknown Approved Use Unknown
Breast cancer 434 Sources: http://adisinsight.springer.com/drugs/800028881	Primary	Phase III 656	Unknown Approved Use Unknown
Fallopian tube cancer 17 Sources: http://adisinsight.springer.com/drugs/800028881	Primary	Phase III 656	Unknown Approved Use Unknown
Peritoneal cancer 11 Sources: http://adisinsight.springer.com/drugs/800028881	Primary	Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
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
804 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/208447s014lbl.pdf	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

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

T_1/2

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

F_unbound

Value	Dose	Co-administered	Analyte	Population
17% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/208447s014lbl.pdf	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/23810788/	unhealthy, 59 years (range: 39–75 years) n = 6 Health Status: unhealthy Condition: advanced solid tumours Age Group: 59 years (range: 39–75 years) Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/23810788/	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: https://pubmed.ncbi.nlm.nih.gov/23810788/
30 mg 1 times / day steady, oral Dose: 30 mg, 1 times / day Route: oral Route: steady Dose: 30 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23810788/	unhealthy, 59 years (range: 39–75 years) n = 6 Health Status: unhealthy Condition: advanced solid tumours Age Group: 59 years (range: 39–75 years) Sex: M+F Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/23810788/	DLT: Fatigue... Dose limiting toxicities: Fatigue (grade 3, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/23810788/
60 mg 1 times / day steady, oral Dose: 60 mg, 1 times / day Route: oral Route: steady Dose: 60 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/23810788/	unhealthy, 59 years (range: 39–75 years) n = 7 Health Status: unhealthy Condition: advanced solid tumours Age Group: 59 years (range: 39–75 years) Sex: M+F Population Size: 7 Sources: https://pubmed.ncbi.nlm.nih.gov/23810788/	DLT: Pneumonitis... Dose limiting toxicities: Pneumonitis (grade 3, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/23810788/
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208447lbl.pdf	unhealthy n = 367 Health Status: unhealthy Condition: platinum-sensitive recurrent ovarian cancer \| fallopian tube cancer\|primary peritoneal cancer Population Size: 367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208447lbl.pdf	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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208447lbl.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781	inhibitor 1767	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OCT1 512 BCRP 699 OATP1B1 788 OATP1B3 706 OAT1 599 OAT3 642 OCT2 647 BSEP 402 CYP1A 72 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP3A4/5 278 P-gp 1461 MATE1 306 MATE2 263	BCRP 561 P-gp 1537 CYP1A2 1054 CYP3A4/5 85 UGT 192 OATP1B1 406 OATP1B3 350 OCT1 327 OAT1 326 OAT3 339 OCT2 355 BSEP 52 MATE1 135 MATE2 96	CYP1A2 701

Drug as perpetrator

Target	Modality	Activity	Metabolite
BCRP 773	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no	M1 8
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208447Orig1s000MultidisciplineR.pdf#page=90 Page: 90.0	no
BSEP 403	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no	M1 8
CYP1A 121	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no
CYP1A 121	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no	M1 8
CYP1A2 1692	inducer 1573 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no	M1 8
CYP2B6 1001	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no	M1 8
CYP2C19 1553	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no	M1 8
CYP2C8 965	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no
CYP2C8 965	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no	M1 8
CYP2C9 1819	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no	M1 8
CYP2D6 1891	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no	M1 8
CYP3A4 1925	inducer 1573 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no
CYP3A4 1925	inducer 1573 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no	M1 8
CYP3A4/5 335	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no
CYP3A4/5 335	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no	M1 8
MATE1 308	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no	M1 8
MATE2 263	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no	M1 8
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208447Orig1s000MultidisciplineR.pdf#page=90 Page: 90.0	no
OAT1 603	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no	M1 8
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208447Orig1s000MultidisciplineR.pdf#page=90 Page: 90.0	no
OAT3 644	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no	M1 8
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208447Orig1s000MultidisciplineR.pdf#page=90 Page: 90.0	no
OATP1B1 803	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no	M1 8
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208447Orig1s000MultidisciplineR.pdf#page=90 Page: 90.0	no
OATP1B3 715	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no	M1 8
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208447Orig1s000MultidisciplineR.pdf#page=90 Page: 90.0	no
OCT2 648	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no	M1 8
P-gp 1650	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no	M1 8
P-gp 1650	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	weak [Inhibition 161 uM]
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208447Orig1s000MultidisciplineR.pdf#page=72 Page: 72.0	weak
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208447Orig1s000MultidisciplineR.pdf#page=72 Page: 72.0	weak
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208447Orig1s000MultidisciplineR.pdf#page=81 Page: 81.0	yes [IC50 1.21 uM]
MATE1 308	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	yes [Inhibition 0.18 uM]
MATE2 263	inhibitor 3277 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	yes [Inhibition <0.14 uM]

Drug as victim

Target	Modality	Activity	Metabolite
BCRP 561	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=43 Page: -	no	M1 13
BSEP 52	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208447Orig1s000MultidisciplineR.pdf#page=90 Page: 90.0	no
BSEP 52	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no	M1 13
MATE1 135	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=43 Page: -	no
MATE2 96	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=43 Page: -	no
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208447Orig1s000MultidisciplineR.pdf#page=90 Page: 90.0	no
OAT1 326	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no	M1 13
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208447Orig1s000MultidisciplineR.pdf#page=90 Page: 90.0	no
OAT3 339	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no	M1 13
OATP1B1 406	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208447Orig1s000MultidisciplineR.pdf#page=90 Page: 90.0	no
OATP1B1 406	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=43 Page: -	no	M1 13
OATP1B3 350	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208447Orig1s000MultidisciplineR.pdf#page=90 Page: 90.0	no
OATP1B3 350	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=43 Page: -	no	M1 13
OCT1 327	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208447Orig1s000MultidisciplineR.pdf#page=90 Page: 90.0	no
OCT1 327	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=43 Page: -	no	M1 13
OCT2 355	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208447Orig1s000MultidisciplineR.pdf#page=90 Page: 90.0	no
OCT2 355	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=42 Page: -	no	M1 13
P-gp 1537	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=43 Page: -	no	M1 13
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208447Orig1s000MultidisciplineR.pdf#page=72 Page: 72.0	yes
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208447Orig1s000MultidisciplineR.pdf#page=89 Page: 89.0	yes
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208447Orig1s000MultidisciplineR.pdf#page=89 Page: 89.0	yes
CYP3A4/5 85	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208447Orig1s000MultidisciplineR.pdf#page=89 Page: 89.0	yes
MATE1 135	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=43 Page: -	yes	M1 13
MATE2 96	substrate 3367 Sources: https://www.ema.europa.eu/en/documents/assessment-report/zejula-epar-public-assessment-report_en.pdf#page=43 Page: -	yes	M1 13
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208447Orig1s000MultidisciplineR.pdf#page=72 Page: 72.0	yes
UGT 192	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208447Orig1s000MultidisciplineR.pdf#page=89 Page: 89.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208447Orig1s000MultidisciplineR.pdf#page=30 Page: 30.0

Sourcing

Vendor/Aggregator	ID	URL
AA Blocks	AA0038X2	https://www.aablocks.com/goods/Goods/detail?id=AA0038X2
AK Scientific, Inc. (AKSCI)	0919AA	http://www.aksci.com/item_detail.php?cat=0919AA
Aaron Chemicals	AR0039OU	http://www.aaronchem.com/1038915-60-4
AbMole Bioscience	M2215	http://www.abmole.com/products/mk-4827.html
Achemo Scientific Limited	AC-86985	http://www.achemo.com/search/?Keyword= 1038915-60-4
Achemtek	0102-029640	http://www.achemtek.com/1038915-60-4
Adooq BioScience	MK-4827	http://www.adooq.com/mk-4827.html
Adooq BioScience	A11026	https://www.adooq.com/mk-4827.html
Ambinter	Amb22388574	http://www.ambinter.com/reference/22388574
Angene	AGN-PC-0OSO5V	http://www.angenechemical.com/productshow/AGN-PC-0OSO5V.html
Anward	ANW-62065	http://www.anward.com/pro_result/48516
ApexBio Technology	A3617	http://www.apexbt.com/mk-9380.html
Aurum Pharmatech LLC	W-5696	http://www.Aurumpharmatech.com/Product/ProductDetails/W_5696
Axon MedChem	2928	https://www.axonmedchem.com/product/2928
BLD Pharm	BD234046	http://www.bldpharm.com/products/1038915-60-4.html
BioCrick	BCC1761	http://www.biocrick.com/MK-4827-BCC1761.html
CSNpharm	CSN13146	https://www.csnpharm.com/products/mk-4827.html
Chem Scene	CS-0780	http://www.chemscene.com/1038915-60-4.html
Chemspace	CSSB00015193672	https://chem-space.com/CSSB00015193672
DAOGE BIOPHARMA	DG21-13343	https://www.daogechem.com/product/1038915-60-4.html
Excenen	EX-A290	http://www.excenen.com/searchresultlist.php?id=1038915-60-4
Lab Network	LN01331029	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01331029
Matrix Scientific	153552	https://www.matrixscientific.com/153552.html
MedChem Express	HY-10619	https://www.medchemexpress.com/MK-4827.html
Smolecule	S537248	http://www.smolecule.com/products/s537248
Smolecule	S746643	https://www.smolecule.com/products/s746643
Synblock Inc	SB16547	http://www.synblock.com/product/1038915-60-4.html
THE BioTek	bt-277148	https://www.thebiotek.com/product/inhibitors/bt-277148
Tenova Pharmaceuticals Inc	T31004	https://www.tenovapharma.com/Niraparib
Yuhao Chemical	YH65274	http://www.chemyuhao.com/1038915-60-4.html
abcr GmbH	AB435856	http://www.abcr.com/shop/en/AB435856
eNovation Chemicals	D388300	http://www.enovationchem.com/productDetails.asp?productID=D388300
iChemical	EBD2206766	http://www.ichemical.com/products/1038915-60-4.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy.	2005 Apr 14	15829967
Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase.	2005 Apr 14	15829966
Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers.	2009 Jul 9	19553641
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	19873981
Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors.	2012 Nov 1	23118055
The Role of PARP Inhibitors in the Treatment of Gynecologic Malignancies.	2013 Oct 1	24098868

Patents

Sample Use Guides

In Vivo Use Guide

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

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 Dec 16 09:12:11 GMT 2023` Edited by `admin` on `Sat Dec 16 09:12:11 GMT 2023`
Record UNII	195Q483UZD
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

Niraparib tosylate monohydrate

Common Name

English

ZEJULA

Brand Name

English

AKEEGA COMPONENT NIRAPARIB TOSYLATE MONOHYDRATE

Brand Name

English

2H-Indazole-7-carboxamide, 2-[4-(3S)-3-piperidinylphenyl]-, 4-methylbenzenesulfonate, hydrate (1:1:1)

Systematic Name

English

MK-4827 TOSYLATE MONOHYDRATE

Code

English

NIRAPARIB TOSILATE HYDRATE

Common Name

English

NIRAPARIB TOSYLATE MONOHYDRATE COMPONENT OF AKEEGA

Brand Name

English

NIRAPARIB TOSYLATE MONOHYDRATE [MI]

Common Name

English

NIRAPARIB TOSILATE HYDRATE [JAN]

Common Name

English

Niraparib tosylate monohydrate [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C62554