MK-4827 tosylate
MK-4827 tosylate structure
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Common Name | MK-4827 tosylate | ||
|---|---|---|---|---|
| CAS Number | 1038915-73-9 | Molecular Weight | 492.59000 | |
| Density | N/A | Boiling Point | N/A | |
| Molecular Formula | C26H28N4O4S | Melting Point | N/A | |
| MSDS | N/A | Flash Point | N/A | |
Use of MK-4827 tosylateNiraparib tosylate (MK-4827 tosylate) is an excellent PARP1 and PARP2 inhibitor with an IC50 of 3.8 and 2.1 nM, respectively. |
Summary: Niraparib p-toluenesulfonate (common name: MK-4827 tosylate), with the chemical name (3S)-3-[4-[7-(carbamoyl)-2H-indazole-2-yl]phenyl]piperidine p-toluenesulfonate, has a molecular formula of C26H28N4O4S and a molecular weight of 492.59000, with a CAS number of 1038915-73-9. This compound is an effective PARP1 and PARP2 inhibitor with IC50 values of 3.8 nM and 2.1 nM, respectively. For research-use only, not for medical or clinical usage.
This table lists Chinese names, IUPAC names and various aliases of this chemical substance.
| Name | niraparib p-toluenesulfonate |
|---|---|
| Synonym | More Synonyms |
This table contains bioactivity, target information and biological‑assay experimental data of this compound.
| Description | Niraparib tosylate (MK-4827 tosylate) is an excellent PARP1 and PARP2 inhibitor with an IC50 of 3.8 and 2.1 nM, respectively. |
|---|---|
| Related Catalog | |
| Target |
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) |
| In Vitro | Niraparib (MK-4827) inhibits PARP activity with EC50=4 nM and EC90=45 nM in a whole cell assay. MK-4827 inhibits proliferation of cancer cells with mutant BRCA-1 and BRCA-2 with CC50 in the 10−100 nM range. MK-4827 displays excellent PARP 1 and 2 inhibition with IC50=3.8 and 2.1 nM, respectively, and in a whole cell assay[1]. To validate that Niraparib (MK-4827) inhibits PARP in these cell lines, A549 and H1299 cells are treated with 1 μM Niraparib (MK-4827) for various times and measured PARP enzymatic activity using a chemiluminescent assay. The results show that Niraparib (MK-4827) 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[2]. |
| In Vivo | Niraparib (MK-4827) is well tolerated and demonstrates efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer. Niraparib (MK-4827) is well tolerated in vivo and demonstrates efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer. Niraparib (MK-4827) is characterized by acceptable pharmacokinetics in rats with plasma clearance of 28 (mL/min)/kg, very high volume of distribution (Vdss=6.9 L/kg), long terminal half-life (t1/2=3.4 h), and excellent bioavailability, F=65%[1]. Niraparib (MK-4827) enhances radiation response of p53 mutant Calu-6 tumor in both cases, with the single daily dose of 50 mg/kg being more effective than 25 mg/kg given twice daily[3]. |
| Cell Assay | The inhibition of PARP is analyzed in A549 and H1299 cells using the HT Universal Chemiluminescent PARP Assay Kit. Briefly, cells are treated with DMSO or 1 μM Niraparib (MK-4827) for 15, 30, 60, or 120 minutes, trypsinized, and transferred to a pre-chilled tube. The cells are washed twice with ice cold PBS and resuspended in cold PARP extraction buffer. The cell suspensions are incubated on ice for 30 minutes with periodic vortexing to disrupt the cell membrane. The suspensions are centrifuged and the supernatant transferred to a pre-chilled tube on ice. The histone coated wells of the 96-well plate are rehydrated with 1X PARP buffer and incubated at room temperature for 30 minutes. The PARP buffer is removed and 20 μg of protein as determined by the Bio-Rad Protein Assay is added to each well followed by diluted PARP-HSA enzyme and 1X PARP buffer. The strip wells are then incubated at room temperature for 60 minutes, washed twice with PBS containing 0.1% Triton X-100, and then washed with PBS. Diluted Strep-HRP is added to the strip wells and incubated for 60 minutes at room temperature. The wells are washed again as before. Equal volumes of PeroxyGlow A and B are combined and added to the wells and chemiluminescent readings are obtained immediately using a plate-reader[2]. |
| Animal Admin | Mice[3] Female nude mice (Ncr Nu/Nu) are randomly assigned to treatment groups consisting of 5 to 8 mice each when tumors grew to 6.0 mm in diameter at which time treatment with MK-4827 is initiated. MK-4827 is given at a dose of 25 mg/kg twice daily or 50 mg/kg once daily for either 21 days or is discontinued at 9 days from the time tumors reached 8 mm in diameter. Fractionated local tumor irradiation (XRT) is given when tumors reach 8.0 mm in diameter (7.7-8.2 mm). Radiation (2 Gy per fraction) is delivered to the tumor-bearing leg of mice once daily for 14 consecutive days or twice daily for 7 consecutive days using a small-animal irradiator consisting of two parallel-opposed 137Cs sources, at a dose rate of 5 Gy/min. During irradiation un-anesthetized mice are mechanically immobilized in a jig so that the tumor is centered within a 3.0 cm diameter radiation field and the animal’s body shielded from radiation exposure. On the day when both MK-4827 and radiation are given, drug is administered 1 h before the first radiation dose of the day. |
| References |
This table shows physicochemical parameters including melting point, boiling point, density, solubility and optical rotation. Missing data is marked as N/A.
| Molecular Formula | C26H28N4O4S |
|---|---|
| Molecular Weight | 492.59000 |
| Exact Mass | 492.18300 |
| PSA | 135.69000 |
| LogP | 5.94300 |
| Storage condition | -20℃ |
This table presents publicly reported synthetic routes, reaction conditions, reactants and product information of the compound.
This table lists upstream starting materials and downstream derivative products related to this chemical.
| Precursor 1 | |
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| DownStream 0 | |
This table contains target information, in‑vitro & in‑vivo assay data for this compound.
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Name: Synergistic antiproliferative activity against human A549 cells pretreated with MS023...
Source: ChEMBL
Target: A549
External Id: CHEMBL5715208
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Name: Antiproliferative against human A549 cells assessed as reduction in cell viability pr...
Source: ChEMBL
Target: A549
External Id: CHEMBL5715211
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Name: Antiproliferative against human A549 cells assessed as cell viability at 10 uM for 24...
Source: ChEMBL
Target: A549
External Id: CHEMBL5715212
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Name: Synergistic antiproliferative activity against human A549 cells assessed as synergy i...
Source: ChEMBL
Target: A549
External Id: CHEMBL5715215
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Name: Antiproliferative against human A549 cells assessed as viable cells pretreated with M...
Source: ChEMBL
Target: A549
External Id: CHEMBL5715214
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This table collects all English aliases, systematic names and CAS‑related synonyms of the compound.
| MK-4827 tosylate |
| MK-4827 (tosylate) |
| Niraparib Tosylate |
This section contains frequently‑asked‑questions about this compound, including basic parameters, properties, storage conditions and corresponding answers.
| Q: What is the CAS number of niraparib p-toluenesulfonate? |
| A: CAS number of niraparib p-toluenesulfonate is 1038915-73-9. |
| Q: What are the uses of niraparib p-toluenesulfonate? |
| A: Main uses of niraparib p-toluenesulfonate: Niraparib tosylate (MK-4827 tosylate) is an excellent PARP1 and PARP2 inhibitor with an IC50 of 3.8 and 2.1 nM, respectively. |
| Q: What is the molecular weight of niraparib p-toluenesulfonate? |
| A: Molecular weight of niraparib p-toluenesulfonate is 492.59000. |
| Q: What are the upstream materials of niraparib p-toluenesulfonate? |
| A: Related upstream materials(CAS) of niraparib p-toluenesulfonate: 108-86-1. |
| Q: What are the storage conditions for niraparib p-toluenesulfonate? |
| A: Storage conditions for niraparib p-toluenesulfonate: -20℃. |
| Q: What is the polar surface area (PSA) of niraparib p-toluenesulfonate? |
| A: Polar surface area (PSA) of niraparib p-toluenesulfonate is 135.69000. |
| Q: What is the molecular formula of niraparib p-toluenesulfonate? |
| A: Molecular formula of niraparib p-toluenesulfonate is C26H28N4O4S. |
| Q: What is the LogP of niraparib p-toluenesulfonate? |
| A: LogP of niraparib p-toluenesulfonate is 5.94300. |
| Q: What is the English name of niraparib p-toluenesulfonate? |
| A: The English name of niraparib p-toluenesulfonate is niraparib p-toluenesulfonate. |
| Q: What English synonyms does niraparib p-toluenesulfonate have? |
| A: English synonyms of niraparib p-toluenesulfonate: MK-4827 tosylate, MK-4827 (tosylate), Niraparib Tosylate. |
This table lists manufacturers and suppliers of this compound, including vendor names and product supply reference information.
| Shanghai Nianxing Industrial Co., Ltd |
| Dayang Chem (Hangzhou) Co., Ltd. |