Niraparib HCl
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MedKoo CAT#: 201916

CAS#: 1038915-64-8 (HCl)

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.


Price and Availability

Size
Price

100mg
USD 950
1g
USD 3850
Size
Price

200mg
USD 1650
2g
USD 5950
Size
Price

500mg
USD 2650
5g
USD 8950

Niraparib HCl, purity > 98%, is in stock. Current shipping out time is about 2 weeks after order is received. CoA, QC data and MSDS documents are available in one week after order is received.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 201916
Name: Niraparib HCl
CAS#: 1038915-64-8 (HCl)
Chemical Formula: C19H21ClN4O
Exact Mass: 356.1404
Molecular Weight: 356.854
Elemental Analysis: C, 63.95; H, 5.93; Cl, 9.93; N, 15.70; O, 4.48


Related CAS #: 1038915-60-4 (free base)   1038915-64-8 (HCl)   1038915-73-9 (tosylate)   1613220-15-7 (tosylate hydrate)  

Synonym: MK4827; MK 4827; MK4827; Niraparib; Niraparib HCl; Niraparib hydrochloride.

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

InChi Key: YXYDNYFWAFBCAN-PFEQFJNWSA-N

InChi Code: 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

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


Technical Data

Appearance:
Light yellow 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, not in water

Shelf Life:
>2 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).

Harmonized System Code:
293490


Additional Information

Related CAS#
CAS#1038915-60-4 ( Niraparib free base);
CAS#1038915-64-8 ( Niraparib HCl salt);
CAS#1038915-73-9 ( Niraparib tosylate)

MK-4827 displays good pharmacokinetic properties and is currently in phase I clin. trials. This compd. displays excellent PARP 1 and 2 inhibition with IC50 = 3.8 and 2.1 nM, resp., and in a whole cell assay, it inhibited PARP activity with EC50 = 4 nM and inhibited proliferation of cancer cells with mutant BRCA-1 and BRCA-2 with CC50 in the 10-100 nM range. MK-4827 was well tolerated in vivo and demonstrated efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer.  [See: Journal of Medicinal Chemistry (2009), 52(22), 7170-7185. ]
 
MK-4827 was found to be highly and similarly effective in both radiation schedules but maximum radiation enhancement was observed when MK-4827 was given at a dose of 50 mg/kg once daily (EF = 2.2). MK-4827 radiosensitized all four tumors studied regardless of their p53 status. MK-4827 reduced PAR levels in tumors by 1 h after administration which persisted for up to 24 h. This long period of PARP inhibition potentially adds to the flexibility of design of future clinical trials. Thus, MK-4827 shows high potential to improve the efficacy of radiotherapy. (source: Invest New Drugs. 2011 Nov 30. [Epub ahead of print])
 


References

1: Ledermann JA. PARP inhibitors in ovarian cancer. Ann Oncol. 2016 Apr;27 Suppl 1:i40-i44. doi: 10.1093/annonc/mdw094. PubMed PMID: 27141070.

2: Kaye SB. Progress in the treatment of ovarian cancer-lessons from homologous recombination deficiency-the first 10 years. Ann Oncol. 2016 Apr;27 Suppl 1:i1-i3. doi: 10.1093/annonc/mdw082. PubMed PMID: 27141062; PubMed Central PMCID: PMC4852273.

3: Jenner ZB, Sood AK, Coleman RL. Evaluation of rucaparib and companion diagnostics in the PARP inhibitor landscape for recurrent ovarian cancer therapy. Future Oncol. 2016 Jun;12(12):1439-56. doi: 10.2217/fon-2016-0002. Epub 2016 Apr 18. PubMed PMID: 27087632.

4: Liu JF, Matulonis UA. What Is the Place of PARP Inhibitors in Ovarian Cancer Treatment? Curr Oncol Rep. 2016 May;18(5):29. doi: 10.1007/s11912-016-0515-z. Review. PubMed PMID: 26984416.

5: Alotaibi M, Sharma K, Saleh T, Povirk LF, Hendrickson EA, Gewirtz DA. Radiosensitization by PARP Inhibition in DNA Repair Proficient and Deficient Tumor Cells: Proliferative Recovery in Senescent Cells. Radiat Res. 2016 Mar;185(3):229-45. doi: 10.1667/RR14202.1. Epub 2016 Mar 2. PubMed PMID: 26934368; PubMed Central PMCID: PMC4821451.

6: Ekblad T, Schüler H. Sirtuins are Unaffected by PARP Inhibitors Containing Planar Nicotinamide Bioisosteres. Chem Biol Drug Des. 2016 Mar;87(3):478-82. doi: 10.1111/cbdd.12680. Epub 2015 Nov 26. PubMed PMID: 26518726.

7: McGonigle S, Chen Z, Wu J, Chang P, Kolber-Simonds D, Ackermann K, Twine NC, Shie JL, Miu JT, Huang KC, Moniz GA, Nomoto K. E7449: A dual inhibitor of PARP1/2 and tankyrase1/2 inhibits growth of DNA repair deficient tumors and antagonizes Wnt signaling. Oncotarget. 2015 Dec 1;6(38):41307-23. doi: 10.18632/oncotarget.5846. PubMed PMID: 26513298; PubMed Central PMCID: PMC4747407.

8: Engert F, Schneider C, Weiβ LM, Probst M, Fulda S. PARP Inhibitors Sensitize Ewing Sarcoma Cells to Temozolomide-Induced Apoptosis via the Mitochondrial Pathway. Mol Cancer Ther. 2015 Dec;14(12):2818-30. doi: 10.1158/1535-7163.MCT-15-0587. Epub 2015 Oct 5. PubMed PMID: 26438158.

9: Chornenkyy Y, Agnihotri S, Yu M, Buczkowicz P, Rakopoulos P, Golbourn B, Garzia L, Siddaway R, Leung S, Rutka JT, Taylor MD, Dirks PB, Hawkins C. Poly-ADP-Ribose Polymerase as a Therapeutic Target in Pediatric Diffuse Intrinsic Pontine Glioma and Pediatric High-Grade Astrocytoma. Mol Cancer Ther. 2015 Nov;14(11):2560-8. doi: 10.1158/1535-7163.MCT-15-0282. Epub 2015 Sep 8. PubMed PMID: 26351319.

10: Seimiya H. [Cancer therapy by PARP inhibitors]. Nihon Rinsho. 2015 Aug;73(8):1330-5. Review. Japanese. PubMed PMID: 26281686.

11: Hopkins TA, Shi Y, Rodriguez LE, Solomon LR, Donawho CK, DiGiammarino EL, Panchal SC, Wilsbacher JL, Gao W, Olson AM, Stolarik DF, Osterling DJ, Johnson EF, Maag D. Mechanistic Dissection of PARP1 Trapping and the Impact on In Vivo Tolerability and Efficacy of PARP Inhibitors. Mol Cancer Res. 2015 Nov;13(11):1465-77. doi: 10.1158/1541-7786.MCR-15-0191-T. Epub 2015 Jul 27. PubMed PMID: 26217019.

12: Jones P, Wilcoxen K, Rowley M, Toniatti C. Niraparib: A Poly(ADP-ribose) Polymerase (PARP) Inhibitor for the Treatment of Tumors with Defective Homologous Recombination. J Med Chem. 2015 Apr 23;58(8):3302-14. doi: 10.1021/jm5018237. Epub 2015 Mar 11. PubMed PMID: 25761096.

13: Shen Y, Aoyagi-Scharber M, Wang B. Trapping Poly(ADP-Ribose) Polymerase. J Pharmacol Exp Ther. 2015 Jun;353(3):446-57. doi: 10.1124/jpet.114.222448. Epub 2015 Mar 10. PubMed PMID: 25758918.

14: Genther Williams SM, Kuznicki AM, Andrade P, Dolinski BM, Elbi C, O'Hagan RC, Toniatti C. Treatment with the PARP inhibitor, niraparib, sensitizes colorectal cancer cell lines to irinotecan regardless of MSI/MSS status. Cancer Cell Int. 2015 Feb 4;15(1):14. doi: 10.1186/s12935-015-0162-8. eCollection 2015. PubMed PMID: 25685067; PubMed Central PMCID: PMC4326439.

15: Bridges KA, Toniatti C, Buser CA, Liu H, Buchholz TA, Meyn RE. Niraparib (MK-4827), a novel poly(ADP-Ribose) polymerase inhibitor, radiosensitizes human lung and breast cancer cells. Oncotarget. 2014 Jul 15;5(13):5076-86. PubMed PMID: 24970803; PubMed Central PMCID: PMC4148123.

16: Liu JF, Konstantinopoulos PA, Matulonis UA. PARP inhibitors in ovarian cancer: current status and future promise. Gynecol Oncol. 2014 May;133(2):362-9. doi: 10.1016/j.ygyno.2014.02.039. Epub 2014 Mar 4. Review. PubMed PMID: 24607283.

17: Murai J, Huang SY, Renaud A, Zhang Y, Ji J, Takeda S, Morris J, Teicher B, Doroshow JH, Pommier Y. Stereospecific PARP trapping by BMN 673 and comparison with olaparib and rucaparib. Mol Cancer Ther. 2014 Feb;13(2):433-43. doi: 10.1158/1535-7163.MCT-13-0803. Epub 2013 Dec 19. PubMed PMID: 24356813; PubMed Central PMCID: PMC3946062.

18: Reinbolt RE, Hays JL. The Role of PARP Inhibitors in the Treatment of Gynecologic Malignancies. Front Oncol. 2013 Oct 1;3:237. doi: 10.3389/fonc.2013.00237. Review. PubMed PMID: 24098868; PubMed Central PMCID: PMC3787651.

19: Postel-Vinay S, Bajrami I, Friboulet L, Elliott R, Fontebasso Y, Dorvault N, Olaussen KA, André F, Soria JC, Lord CJ, Ashworth A. A high-throughput screen identifies PARP1/2 inhibitors as a potential therapy for ERCC1-deficient non-small cell lung cancer. Oncogene. 2013 Nov 21;32(47):5377-87. doi: 10.1038/onc.2013.311. Epub 2013 Aug 12. PubMed PMID: 23934192.

20: Infante JR, Burris HA 3rd. PARP inhibitors: pitfalls and promises. Lancet Oncol. 2013 Aug;14(9):798-9. doi: 10.1016/S1470-2045(13)70276-6. Epub 2013 Jun 28. PubMed PMID: 23810789.