Niraparib

Niraparib

Niraparib
Clinical data
Routes of
administration		 Oral
Legal status
Legal status
Identifiers
CAS Number 1038915-60-4 YesY
PubChem (CID) 24958200
ChemSpider 24531930 YesY
UNII HMC2H89N35 YesY
ChEMBL CHEMBL1094636 YesY
Chemical and physical data
Formula C19H20N4O
Molar mass 320.394 g/mol
3D model (Jmol) Interactive image

Niraparib (originally MK-4827)[1] is an orally active[2] small molecule PARP inhibitor being developed (by Tesaro) to treat ovarian cancer.

It is an inhibitor of PARP1 and PARP2.[3]

Niraparib is due to be submitted for FDA approval (for maintenance therapy in ovarian cancer) later in 2016.[4]

Chemically MK-4827 is C19H20N4O[5] (ignoring a possible tosylate group).[6]

A 2012 study found that PARP inhibitors exhibit cytotoxic effects not based solely on their enzymatic inhibition of PARP, but by their trapping of PARP on damaged DNA, and the strength of this trapping activity was ordered niraparib >> olaparib >> veliparib.[7]

Clinical trials

It has undergone a phase III trial for ovarian cancer.[8] It is reported that the primary endpoint (progression-free survival, PFS) was met.[4] Patients with and without a BRCA mutation both showed longer PFS.[4]

As of June 2016 seven clinical trials have been registered for MK-4827.[9]

References

  1. ↑ "PARP Inhibitors in Oncology. Chemosensitizers or Single-Agent Therapeutics?" (PDF). July 2009.
  2. ↑ A Phase III Trial of Niraparib Versus Physician's Choice in HER2 Negative, Germline BRCA Mutation-positive Breast Cancer Patients (BRAVO)
  3. ↑ "PARP inhibitor, MK-4827, shows anti-tumor activity in first trial in humans". 17 Nov 2010.
  4. 1 2 3 Tesaro’s PARP ovarian cancer drug hits PhIII goal; prepares to file. June 2016
  5. ↑ MK-4827 @ pubchem
  6. ↑ MK-4827
  7. ↑ Murai, Junko, et al. "Trapping of PARP1 and PARP2 by clinical PARP inhibitors." Cancer research 72.21 (2012): 5588-5599.
  8. ↑ AbbVie takes PARP inhibitor into third phase III trial. June 2014
  9. ↑ Niraparib studies

Further reading


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