Niraparib tosylate hydrate
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MedKoo CAT#: 330234

CAS#: 1613220-15-7 (tosylate hydrate)

Description: Niraparib, also know as MK-4827, is an inhibitor of poly (ADP-ribose) polymerase (PARP) with potential antineoplastic activity. MK4827 inhibits PARP activity, enhancing the accumulation of DNA strand breaks and promoting genomic instability and apoptosis. The PARP family of proteins detect and repair single strand DNA breaks by the base-excision repair (BER) pathway.


Chemical Structure

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Niraparib tosylate hydrate
CAS# 1613220-15-7 (tosylate hydrate)

Theoretical Analysis

MedKoo Cat#: 330234
Name: Niraparib tosylate hydrate
CAS#: 1613220-15-7 (tosylate hydrate)
Chemical Formula: C26H30N4O5S
Exact Mass: 0.00
Molecular Weight: 510.609
Elemental Analysis: C, 61.16; H, 5.92; N, 10.97; O, 15.67; S, 6.28

Price and Availability

Size Price Availability Quantity
200mg USD 450 2 weeks
500mg USD 850 2 weeks
1g USD 1450 2 weeks
2g USD 2450 2 weeks
5g USD 5850 2 weeks
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Related CAS #: 1038915-73-9 (tosylate)   1038915-60-4 (free base)   1038915-64-8 (HCl)   1613220-15-7 (tosylate hydrate)   1038915-58-0    

Synonym: Niraparib tosylate hydrate; MK-4827; MK-4827; MK4827; MK4827-tosylate; Niraparib tosylate;

IUPAC/Chemical Name: (S)-2-(4-(piperidin-3-yl)phenyl)-2H-indazole-7-carboxamide 4-methylbenzenesulfonate hydrate

InChi Key: ACNPUCQQZDAPJH-FMOMHUKBSA-N

InChi Code: 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

SMILES Code: O=C(C1=CC=CC2=CN(C3=CC=C([C@H]4CNCCC4)C=C3)N=C12)N.O=S(C5=CC=C(C)C=C5)(O)=O.[H]O[H]

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >3 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Product Data:
Biological target: Niraparib (MK-4827) tosylate hydrate is a highly potent and orally bioavailable PARP1 and PARP2 inhibitor with IC50s of 3.8 and 2.1 nM.
In vitro activity: This study aimed to explore the genomic and molecular landscape of BRCAness using whole exome sequencing (WES) in STS, aiming to find a potential target for STS treatment. To reveal the possible genomic and molecular characteristics of STS, analyses were performed in 22 STS tumor samples from the First Affiliated Hospital of Sun Yat-sen University by comparing with their matched normal adjacent tissues using WES. DNA damage was induced by a topoisomerase II inhibitor (etoposide) and PARPi niraparib (MK4827) in normal fibroblasts and STS cell lines (HT-1080, RD, SW982, VA-ES-BJ, SK-LMS-1, SW872). We subsequently investigated the potency of niraparib (MK4827) in STS in vitro using MTT assays (Figure S3A). The MTT assay results showed that STS cell lines were sensitive to MK4827. Moreover, with the downregulation of PARP-1 expression, fibroblasts were less sensitive to MK4827 than STS cell lines. Among the five FDA-approved PARPis, niraparib was a more potent and less cytotoxic PARPi for STS treatment. Moreover, according to the screening combination test for cytotoxic regimens therapy for STS (doxorubicin, ifosfamide, dacarbazine, and TMZ), we found that niraparib and TMZ were the most synergistically effective among all STS cell line combination therapies. Our finding provided a novel potential targeted therapeutic strategy for patients with STS. Theranostics. 2020; 10(21): 9477–9494.Published online 2020 Jul 25. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449912/
In vivo activity: To explore whether the biophysical properties intrinsic to niraparib, such as high permeability and VD, may contribute to its broader clinical activity in patients with or without BRCA mutations, the pharmacokinetic profiles and efficacies of niraparib and olaparib were compared in preclinical tumor models. Niraparib was administered at 25, 50, or 75 mg/kg once daily for 28 days to mice bearing MDA-MB-436 BRCAmut tumors. Suppression of tumor growth was observed at all doses with TGIs of 60%, 93%, and 107%, respectively The tissue distribution of niraparib and olaparib were also compared in both the MDA-MB-436 and OVC134 models. After 5-day treatment in the MDA-MB-436 model or 2-day treatment in the OVC134 model, niraparib tumor exposure was 3.3-fold of plasma exposure (Figure 2A & 2C and Table 3), suggesting that niraparib tends to concentrate in tumor relative to plasma. Niraparib demonstrated greater efficacy compared to olaparib in vivo, a phenotype that could, at least partially, be attributed to their different pharmacokinetic properties, i.e. VD and cell permeability. This may also explain why niraparib has shown stronger activity in non-BRCAmut patients in clinical studies. Our results show that niraparib tumor exposure is significantly higher than plasma exposure, which is consistent with its high VD. In comparison, olaparib tumor exposure is lower than plasma exposure. In addition, niraparib permeates the brain, whereas olaparib shows very limited brain exposure at maximum tolerated dose (MTD). Importantly, in BRCAwt tumor xenograft models and an intracranial tumor model, niraparib achieved more potent tumor growth inhibition than olaparib. Oncotarget. 2018 Dec 14; 9(98): 37080–37096.Published online 2018 Dec 14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324689/

Preparing Stock Solutions

The following data is based on the product molecular weight 510.61 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Sambade MJ, Van Swearingen AED, McClure MB, Deal AM, Santos C, Sun K, Wang J, Mikule K, Anders CK. Efficacy and pharmacodynamics of niraparib in BRCA-mutant and wild-type intracranial triple-negative breast cancer murine models. Neurooncol Adv. 2019 Jun 4;1(1):vdz005. doi: 10.1093/noajnl/vdz005. PMID: 32642648; PMCID: PMC7212882. 2. Li H, Tu J, Zhao Z, Chen L, Qu Y, Li H, Yao H, Wang X, Lee DF, Shen J, Wen L, Huang G, Xie X. Molecular signatures of BRCAness analysis identifies PARP inhibitor Niraparib as a novel targeted therapeutic strategy for soft tissue Sarcomas. Theranostics. 2020 Jul 25;10(21):9477-9494. doi: 10.7150/thno.45763. PMID: 32863940; PMCID: PMC7449912. (synergistic) 3. Sun K, Mikule K, Wang Z, Poon G, Vaidyanathan A, Smith G, Zhang ZY, Hanke J, Ramaswamy S, Wang J. A comparative pharmacokinetic study of PARP inhibitors demonstrates favorable properties for niraparib efficacy in preclinical tumor models. Oncotarget. 2018 Dec 14;9(98):37080-37096. doi: 10.18632/oncotarget.26354. PMID: 30647846; PMCID: PMC6324689. 4. AlHilli MM, Becker MA, Weroha SJ, Flatten KS, Hurley RM, Harrell MI, Oberg AL, Maurer MJ, Hawthorne KM, Hou X, Harrington SC, McKinstry S, Meng XW, Wilcoxen KM, Kalli KR, Swisher EM, Kaufmann SH, Haluska P. In vivo anti-tumor activity of the PARP inhibitor niraparib in homologous recombination deficient and proficient ovarian carcinoma. Gynecol Oncol. 2016 Nov;143(2):379-388. doi: 10.1016/j.ygyno.2016.08.328. Epub 2016 Sep 8. PMID: 27614696; PMCID: PMC5370566.
In vitro protocol: 1. Sambade MJ, Van Swearingen AED, McClure MB, Deal AM, Santos C, Sun K, Wang J, Mikule K, Anders CK. Efficacy and pharmacodynamics of niraparib in BRCA-mutant and wild-type intracranial triple-negative breast cancer murine models. Neurooncol Adv. 2019 Jun 4;1(1):vdz005. doi: 10.1093/noajnl/vdz005. PMID: 32642648; PMCID: PMC7212882. 2. Li H, Tu J, Zhao Z, Chen L, Qu Y, Li H, Yao H, Wang X, Lee DF, Shen J, Wen L, Huang G, Xie X. Molecular signatures of BRCAness analysis identifies PARP inhibitor Niraparib as a novel targeted therapeutic strategy for soft tissue Sarcomas. Theranostics. 2020 Jul 25;10(21):9477-9494. doi: 10.7150/thno.45763. PMID: 32863940; PMCID: PMC7449912. (synergistic)
In vivo protocol: 1. Sun K, Mikule K, Wang Z, Poon G, Vaidyanathan A, Smith G, Zhang ZY, Hanke J, Ramaswamy S, Wang J. A comparative pharmacokinetic study of PARP inhibitors demonstrates favorable properties for niraparib efficacy in preclinical tumor models. Oncotarget. 2018 Dec 14;9(98):37080-37096. doi: 10.18632/oncotarget.26354. PMID: 30647846; PMCID: PMC6324689. 2. AlHilli MM, Becker MA, Weroha SJ, Flatten KS, Hurley RM, Harrell MI, Oberg AL, Maurer MJ, Hawthorne KM, Hou X, Harrington SC, McKinstry S, Meng XW, Wilcoxen KM, Kalli KR, Swisher EM, Kaufmann SH, Haluska P. In vivo anti-tumor activity of the PARP inhibitor niraparib in homologous recombination deficient and proficient ovarian carcinoma. Gynecol Oncol. 2016 Nov;143(2):379-388. doi: 10.1016/j.ygyno.2016.08.328. Epub 2016 Sep 8. PMID: 27614696; PMCID: PMC5370566.

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1: Krens S, van der Meulen E, Jansman FGA, Burger DM, van Erp NP. Quantification of cobimetinib, cabozantinib, dabrafenib, niraparib, olaparib, vemurafenib, regorafenib and its metabolite regorafenib M2 in human plasma by UPLC-MS/MS. Biomed Chromatogr. 2019 Nov 22:e4758. doi: 10.1002/bmc.4758. [Epub ahead of print] PubMed PMID: 31758580.

2: Gallagher JR, Heap KJ, Carroll S, Travers K, Harrow B, Westin SN. Real-world adverse events with niraparib 200 mg/day maintenance therapy in ovarian cancer: a retrospective study. Future Oncol. 2019 Dec;15(36):4197-4206. doi: 10.2217/fon-2019-0471. Epub 2019 Nov 11. PubMed PMID: 31707856.

3: Ji Y, Wang Q, Zhao Q, Zhao S, Li L, Sun G, Ye L. Autophagy suppression enhances DNA damage and cell death upon treatment with PARP inhibitor Niraparib in laryngeal squamous cell carcinoma. Appl Microbiol Biotechnol. 2019 Dec;103(23-24):9557-9568. doi: 10.1007/s00253-019-10148-y. Epub 2019 Nov 4. PubMed PMID: 31686145.

4: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK548333/ PubMed PMID: 31643655.

5: Gourd E. Niraparib improves progression-free survival in ovarian cancer. Lancet Oncol. 2019 Nov;20(11):e615. doi: 10.1016/S1470-2045(19)30631-X. Epub 2019 Oct 3. PubMed PMID: 31587884.

6: González-Martín A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, McCormick C, Lorusso D, Hoskins P, Freyer G, Baumann K, Jardon K, Redondo A, Moore RG, Vulsteke C, O'Cearbhaill RE, Lund B, Backes F, Barretina-Ginesta P, Haggerty AF, Rubio-Pérez MJ, Shahin MS, Mangili G, Bradley WH, Bruchim I, Sun K, Malinowska IA, Li Y, Gupta D, Monk BJ; PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2019 Sep 28. doi: 10.1056/NEJMoa1910962. [Epub ahead of print] PubMed PMID: 31562799.

7: Matulonis UA, Walder L, Nøttrup TJ, Bessette P, Mahner S, Gil-Martin M, Kalbacher E, Ledermann JA, Wenham RM, Woie K, Lau S, Marmé F, Casado Herraez A, Hardy-Bessard AC, Banerjee S, Lindahl G, Benigno B, Buscema J, Travers K, Guy H, Mirza MR. Niraparib Maintenance Treatment Improves Time Without Symptoms or Toxicity (TWiST) Versus Routine Surveillance in Recurrent Ovarian Cancer: A TWiST Analysis of the ENGOT-OV16/NOVA Trial. J Clin Oncol. 2019 Dec 1;37(34):3183-3191. doi: 10.1200/JCO.19.00917. Epub 2019 Sep 16. PubMed PMID: 31518175; PubMed Central PMCID: PMC6881097.

8: Mirza MR, Åvall Lundqvist E, Birrer MJ, dePont Christensen R, Nyvang GB, Malander S, Anttila M, Werner TL, Lund B, Lindahl G, Hietanen S, Peen U, Dimoula M, Roed H, Ør Knudsen A, Staff S, Krog Vistisen A, Bjørge L, Mäenpää JU; AVANOVA investigators. Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer (NSGO-AVANOVA2/ENGOT-ov24): a randomised, phase 2, superiority trial. Lancet Oncol. 2019 Oct;20(10):1409-1419. doi: 10.1016/S1470-2045(19)30515-7. Epub 2019 Aug 29. PubMed PMID: 31474354.

9: Gray S, Khor XY, Yiannakis D. Niraparib as maintenance therapy in a patient with ovarian cancer and brain metastases. BMJ Case Rep. 2019 Aug 28;12(8). pii: e230738. doi: 10.1136/bcr-2019-230738. PubMed PMID: 31466953.

10: Zhang J, Zheng H, Gao Y, Lou G, Yin R, Ji D, Li W, Wang W, Xia B, Wang D, Hou J, Yan J, Hei Y, Zhang ZY, Milton A, Wu X. Phase I Pharmacokinetic Study of Niraparib in Chinese Patients with Epithelial Ovarian Cancer. Oncologist. 2019 Aug 22. pii: theoncologist.2019-0565. doi: 10.1634/theoncologist.2019-0565. [Epub ahead of print] PubMed PMID: 31439812.

11: Mirza MR, Bergmann TK, Mau-Sørensen M, Christensen RD, Åvall-Lundqvist E, Birrer MJ, Jørgensen M, Roed H, Malander S, Nielsen F, Lassen U, Brøsen K, Bjørge L, Mäenpää J. A phase I study of the PARP inhibitor niraparib in combination with bevacizumab in platinum-sensitive epithelial ovarian cancer: NSGO AVANOVA1/ENGOT-OV24. Cancer Chemother Pharmacol. 2019 Oct;84(4):791-798. doi: 10.1007/s00280-019-03917-z. Epub 2019 Aug 2. PubMed PMID: 31375879.

12: Konstantinopoulos PA, Waggoner S, Vidal GA, Mita M, Moroney JW, Holloway R, Van Le L, Sachdev JC, Chapman-Davis E, Colon-Otero G, Penson RT, Matulonis UA, Kim YB, Moore KN, Swisher EM, Färkkilä A, D'Andrea A, Stringer-Reasor E, Wang J, Buerstatte N, Arora S, Graham JR, Bobilev D, Dezube BJ, Munster P. Single-Arm Phases 1 and 2 Trial of Niraparib in Combination With Pembrolizumab in Patients With Recurrent Platinum-Resistant Ovarian Carcinoma. JAMA Oncol. 2019 Jun 13. doi: 10.1001/jamaoncol.2019.1048. [Epub ahead of print] PubMed PMID: 31194228; PubMed Central PMCID: PMC6567832.

13: Vinayak S, Tolaney SM, Schwartzberg L, Mita M, McCann G, Tan AR, Wahner-Hendrickson AE, Forero A, Anders C, Wulf GM, Dillon P, Lynce F, Zarwan C, Erban JK, Zhou Y, Buerstatte N, Graham JR, Arora S, Dezube BJ, Telli ML. Open-Label Clinical Trial of Niraparib Combined With Pembrolizumab for Treatment of Advanced or Metastatic Triple-Negative Breast Cancer. JAMA Oncol. 2019 Jun 13. doi: 10.1001/jamaoncol.2019.1029. [Epub ahead of print] PubMed PMID: 31194225; PubMed Central PMCID: PMC6567845.

14: Del Campo JM, Matulonis UA, Malander S, Provencher D, Mahner S, Follana P, Waters J, Berek JS, Woie K, Oza AM, Canzler U, Gil-Martin M, Lesoin A, Monk BJ, Lund B, Gilbert L, Wenham RM, Benigno B, Arora S, Hazard SJ, Mirza MR. Niraparib Maintenance Therapy in Patients With Recurrent Ovarian Cancer After a Partial Response to the Last Platinum-Based Chemotherapy in the ENGOT-OV16/NOVA Trial. J Clin Oncol. 2019 Nov 10;37(32):2968-2973. doi: 10.1200/JCO.18.02238. Epub 2019 Jun 7. PubMed PMID: 31173551; PubMed Central PMCID: PMC6839909.

15: Wallace K, Goble S, Isaacson J, Maloney L, Cameron T, Bedel J. Comment on: "Cost-Effectiveness of Niraparib Versus Routine Surveillance, Olaparib and Rucaparib for the Maintenance Treatment of Patients with Ovarian Cancer in the United States". Pharmacoeconomics. 2019 Aug;37(8):1065-1067. doi: 10.1007/s40273-019-00815-3. PubMed PMID: 31172449; PubMed Central PMCID: PMC6830408.

16: Guy H, Walder L, Fisher M. Response to 'Comment on "Cost-Effectiveness of Niraparib Versus Routine Surveillance, Olaparib and Rucaparib for the Maintenance Treatment of Patients with Ovarian Cancer in the United States"'. Pharmacoeconomics. 2019 Jul;37(7):965-967. doi: 10.1007/s40273-019-00803-7. PubMed PMID: 31044349.

17: McQueen RB, Whittington MD, Chapman RH, Kumar VM, Campbell JD. Comment on "Cost-Effectiveness of Niraparib Versus Routine Surveillance, Olaparib and Rucaparib for the Maintenance Treatment of Patients with Ovarian Cancer in the United States". Pharmacoeconomics. 2019 Jul;37(7):963-964. doi: 10.1007/s40273-019-00802-8. PubMed PMID: 31044348.

18: Moore KN, Secord AA, Geller MA, Miller DS, Cloven N, Fleming GF, Wahner Hendrickson AE, Azodi M, DiSilvestro P, Oza AM, Cristea M, Berek JS, Chan JK, Rimel BJ, Matei DE, Li Y, Sun K, Luptakova K, Matulonis UA, Monk BJ. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019 May;20(5):636-648. doi: 10.1016/S1470-2045(19)30029-4. Epub 2019 Apr 1. Erratum in: Lancet Oncol. 2019 May;20(5):e242. PubMed PMID: 30948273.

19: Neeser K, O'Neil WM, Stern L, Harrow B, Travers K. Budget impact of niraparib as maintenance treatment in recurrent ovarian cancer following platinum-based chemotherapy. J Comp Eff Res. 2019 Jun;8(8):577-587. doi: 10.2217/cer-2018-0069. Epub 2019 Apr 2. PubMed PMID: 30935213.

20: Niraparib Shrinks BRCA-Mutated Prostate Tumors. Cancer Discov. 2019 Apr;9(4):OF7. doi: 10.1158/2159-8290.CD-NB2019-030. Epub 2019 Mar 1. PubMed PMID: 30824427.