MK-4827 (Niraparib) is an oral potent, selective PARP-1 and PARP-2 inhibitor currently in phase I clinical trials for cancer treatment. MK-4827 shows excellent PARP 1 and 2 inhibition with IC(50) = 3.8 and 2.1 nM, respectively, and in a whole cell assay, it inhibited PARP activity with EC(50) = 4 nM and inhibited proliferation of cancer cells with mutant BRCA-1 and BRCA-2 with CC(50) in the 10-100 nM range. MK-4827 reduced PAR levels in tumors by 1 h after administration which persisted for up to 24 h. MK-4827 was well tolerated in vivo and demonstrated efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer. In addition, MK-4827 strongly enhances the effect of radiation on a variety of human tumor xenografts, both p53 wild type and p53 mutant.
Sci Rep. 2023 Feb 27;13(1):3334.
Inhibition of nicotinamide dinucleotide salvage pathway counters acquired and intrinsic poly(ADP-ribose) polymerase inhibitor resistance in high-grade serous ovarian cancer
Niraparib (MK-4827) purchased from AbMole
Nat Commun. 2019 Jun 11;10(1):2556.
Exploiting interconnected synthetic lethal interactions between PARP inhibition and cancer cell reversible senescence.
Niraparib (MK-4827) purchased from AbMole
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Source | Oncotarget (2017). Figure 3. MK-4827 |
| Method | Western blotting | |
| Cell Lines | J45.01 cells | |
| Concentrations | - | |
| Incubation Time | 48 hrs | |
| Results | Similar analysis for DNMT1 showed increased levels of DNMT1 in the chromatin-bound fraction from cells exposed to [DAC+Rom+Npb] compared with cells exposed to [DAC+Rom]; the DNMT1 ratio was 0.25:1 ([DAC+Rom+Npb]:[DAC+Rom]) in the soluble extracts and 2.09:1 in the chromatin-bound fractions |
| Cell Experiment | |
|---|---|
| Cell lines | |
| Preparation method | |
| Concentrations | |
| Incubation time | |
| Animal Experiment | |
|---|---|
| Animal models | Female nude mice (Ncr Nu/Nu) with solitary tumor xenografts |
| Formulation | suspended in 0.5% HPMC in deionized water, mixed for 24 h |
| Dosages | 25 or 50 mg/kg |
| Administration | orally gavage |
| Molecular Weight | 320.39 |
| Formula | C19H20N4O |
| CAS Number | 1038915-60-4 |
| Solubility (25°C) | DMSO ≥ 20 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
| Related PARP Products |
|---|
| DSB-1522
DSB-1522 is a PARP1 inhibitor that can be used in tumor-related studies. |
| DM-5167
DM-5167 is a PARP1 inhibitor that can be used in studies related to triple negative breast cancer. |
| NMS-03305293
NMS-03305293 is a PARP inhibitor with high selectivity for PARP1 isoforms and low DNA capture effect, which specifically kills BRCA mutated tumor cells. In addition, NMS-03305293 can penetrate the blood-brain barrier and can be used in studies related to CNS tumors and brain metastatic tumors. |
| SNV1521
SNV1521 is a potential best-in-class (BIC), highly selective and CNS-permeable PARP1 inhibitor. |
| Basroparib
Basroparib is an orally active selective inhibitor of end-anchor polymerase (TNKS) and an inhibitor of ribose polymerase (PARP) with antitumor activity. |
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