MK-4827 (tosylate) Chemical Properties

Melting point:

>142oC (dec.)

storage temp. 

-20°C Freezer

solubility 

Methanol (Slightly)

form 

Solid

color 

Off-White to Pale Yellow

InChI

InChI=1/C19H20N4O.C7H8O3S/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)/t14-;/s3

InChIKey

LCPFHXWLJMNKNC-XOIICWPPNA-N

SMILES

S(C1C=CC(C)=CC=1)(O)(=O)=O.C(C1=CC=CC2=CN(C3C=CC([C@H]4CNCCC4)=CC=3)N=C12)(=O)N |&1:23,r|

MK-4827 (tosylate) Usage And Synthesis

Description

Niraparib tosylate (MK-4827 tosylate) is a highly potent and orally bioavailable PARP1 and PARP2 inhibitor with an IC50 of 3.8 and 2.1 nM, respectively; with significant activity in cancer cells with mutant BRCA-1 and BRCA-2; >330-fold selective against PARP3, V-PARP, and Tank1. Niraparib tosylate leads to inhibition of repair of DNA damage, activates apoptosis, and shows anti-tumor activity.

Uses

Niraparib is a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors.

in vitro

In a whole-cell assay, Niraparib (MK-4827) tosylate hydrate inhibits PARP activity with EC50=4 nM and EC90=45 nM. Niraparib tosylate hydrate inhibits the proliferation of cancer cells with mutant BRCA-1 and BRCA-2 with CC50 in the 10-100 nM range. Niraparib tosylate hydrate displays excellent PARP 1 and 2 inhibition with IC50=3.8 and 2.1 nM, respectively, and in a whole-cell assay. Niraparib tosylate hydrate inhibits PARP within 15 minutes of treatment, reaching about 85% inhibition in the A549 cells at 1 h and about 55% inhibition at 1 h for the H1299 cells.

in vivo

IC 50

PARP-2: 2.1 nM (IC₅₀); PARP-1: 3.8 nM (IC₅₀); V-PARP: 330 nM (IC₅₀); TANK-1: 570 nM (IC₅₀); PARP-3: 1300 nM (IC₅₀)

References

[1] PHILIP JONES*. 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[J]. Journal of Medicinal Chemistry, 2009, 52 22: 7170-7185. DOI: 10.1021/jm901188v
[2] YUAN YUAN. Novel targeted therapeutics: inhibitors of MDM2, ALK and PARP.[J]. Journal of Hematology & Oncology, 2011, 4: 16. DOI: 10.1186/1756-8722-4-16
[3] LI WANG. MK-4827, a PARP-1/-2 inhibitor, strongly enhances response of human lung and breast cancer xenografts to radiation.[J]. Investigational New Drugs, 2012: 2113-2120. DOI: 10.1007/s10637-011-9770-x
[4] MIRZA M, MONK B, HERRSTEDT J, et al. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer.[J]. The New England Journal of Medicine, 2016, 75 1: 0. DOI: 10.1056/nejmoa1611310

MK-4827 (tosylate)(1038915-73-9)Related Product Information

• (S)-2-(4-(piperidin-3-yl)phenyl)-2H-indazole-7-carboxaMide
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• Nintedanib
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• Tosyl azide
• EGF816 (mesylate)
• Epacadostat (INCB024360)
• Nintedanib Ethanesulfonate Salt
• MK-4827 (R-enantioMer)
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• tert-butyl (S)-3-(4-bromophenyl)piperidine-1-carboxylate
• Niraparib
• Niraparib tosylate
• 3-(4-Bromophenyl)piperidine-1-carboxylic acid tert-butyl ester