Niraparib metabolite M1 is a carboxylic acid metabolite of niraparib (MK4827; Zejula), which is a PARP1/2 inhibitor approved for cancer treatment.

Physicochemical Properties

Molecular Formula	C₁₉H₁₉N₃O₂
Molecular Weight	321.37
Exact Mass	321.147
CAS #	1476777-06-6
Related CAS #	Niraparib;1038915-60-4
PubChem CID	118737587
Appearance	Light brown to brown solid powder
Density	1.3±0.1 g/cm3
Boiling Point	442.0±45.0 °C at 760 mmHg
Flash Point	221.1±28.7 °C
Vapour Pressure	0.0±1.1 mmHg at 25°C
Index of Refraction	1.693
LogP	4.01
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	3
Heavy Atom Count	24
Complexity	450
Defined Atom Stereocenter Count	1
SMILES	C1C[C@H](CNC1)C2=CC=C(C=C2)N3C=C4C=CC=C(C4=N3)C(=O)O
InChi Key	HDQHGRLURKGIFL-CQSZACIVSA-N
InChi Code	InChI=1S/C19H19N3O2/c23-19(24)17-5-1-3-15-12-22(21-18(15)17)16-8-6-13(7-9-16)14-4-2-10-20-11-14/h1,3,5-9,12,14,20H,2,4,10-11H2,(H,23,24)/t14-/m1/s1
Chemical Name	2-[4-[(3S)-piperidin-3-yl]phenyl]indazole-7-carboxylic acid
Synonyms	MK-4827 metabolite M1; Niraparib metabolite M1; 1476777-06-6; UXM824C9GS; UNII-UXM824C9GS; CHEMBL3427055; 2-[4-[(3S)-piperidin-3-yl]phenyl]indazole-7-carboxylic acid; 2H-Indazole-7-carboxylic acid, 2-(4-(3S)-3-piperidinylphenyl)-; Niraparib Carboxylic Acid; Niraparib carboxylic acid metabolite M1; M1 metabolite of niraparib
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Niraparib metabolite
ln Vitro	Niraparib metabolite M1 has the validation in plasma and urine for the support of clinical studies such as the mass balance research and the absolute bioavailability study[1].
ln Vivo	MK-4827, a novel, orally bioavailable, PARP-1 and PARP-2 inhibitor, strongly enhanced the effect of radiation on a variety of human tumor xenografts, both p53 wild type and p53 mutant. It was well tolerated in vivo and demonstrated efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer.
Animal Protocol	Formulated in 0.5% Methocel in deionized water; 25 mg/kg twice daily or 50 mg/kg once daily; Oral gavage Female nude mice
References	[1]. Liquid chromatography-tandem mass spectrometry assay for the quantification of niraparib and its metabolite M1 in human plasma and urine. J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Nov 19;1040:14-21.
Additional Infomation	Niraparib (MK-4827) is a novel poly(ADP-Ribose) polymerase (PARP) inhibitor currently investigated in phase III clinical trials to treat cancers. The development of a new drug includes the characterisation of absorption, metabolism and excretion (AME) of the compound. AME studies are a requirement of regulatory agencies and for this purpose bioanalytical assays are essential. This article describes the development and validation of a bioanalytical assay for niraparib and its carboxylic acid metabolite M1 in human plasma and urine using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Sample pre-treatment involved protein precipitation for plasma and dilution of urine samples using acetonitrile-methanol (50:50, v/v). Final extracts were injected onto a SunFire C18 column and gradient elution using 20mM ammonium acetate (mobile phase A) and formic acid:acetonitrile:methanol (0.1:50:50, v/v/v) (mobile phase B) was applied. Detection was performed on an API5500 tandem mass spectrometer operating in the positive electrospray ionisation mode applying multiple reaction monitoring (MRM). The assay was successfully validated in accordance with the Food and Drug Administration and latest European Medicines Agency guidelines on bioanalytical method validation and can therefore be applied in pharmacological clinical studies. [1]

Solubility Data

Solubility (In Vitro)

DMSO:10 mM Water:<1 mg/mL Ethanol:<1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.75 mg/mL (8.56 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.75 mg/mL (8.56 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.75 mg/mL (8.56 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.1117 mL	15.5584 mL	31.1168 mL
	5 mM	0.6223 mL	3.1117 mL	6.2234 mL
	10 mM	0.3112 mL	1.5558 mL	3.1117 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.