Fluzoparib

CAS No. 1358715-18-0

Fluzoparib( SHR3162, HS10160 )

Catalog No. M22887 CAS No. 1358715-18-0

fluzoparib is a novel, potent, and orally available inhibitor of PARP, potentially for the treatment of solid tumours.Fluzoparib potently inhibited PARP1 enzyme activity and induced DNA double-strand breaks, G2 /M arrest, and apoptosis in homologous recombination repair (HR)-deficient cells.?

Purity : >98% (HPLC)

COA Datasheet HNMR HPLC MSDS Handing Instructions
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Biological Information

  • Product Name
    Fluzoparib
  • Note
    Research use only, not for human use.
  • Brief Description
    fluzoparib is a novel, potent, and orally available inhibitor of PARP, potentially for the treatment of solid tumours.Fluzoparib potently inhibited PARP1 enzyme activity and induced DNA double-strand breaks, G2 /M arrest, and apoptosis in homologous recombination repair (HR)-deficient cells.?
  • Description
    fluzoparib is a novel, potent, and orally available inhibitor of PARP, potentially for the treatment of solid tumours.Fluzoparib potently inhibited PARP1 enzyme activity and induced DNA double-strand breaks, G2 /M arrest, and apoptosis in homologous recombination repair (HR)-deficient cells.?Fluzoparib preferentially inhibited the proliferation of HR-deficient cells and sensitized both HR-deficient and HR-proficient cells to cytotoxic drugs.?Notably, fluzoparib showed good pharmacokinetic properties, favorable toxicity profile, and superior antitumor activity in HR-deficient xenografts models.?Furthermore, fluzoparib in combination with apatinib or with apatinib plus paclitaxel elicited significantly improved antitumor responses without extra toxicity.?In vitro experiments in NSCLC cell lines along with in vivo experiments using an NSCLC xenograft mouse model demonstrated the radiosensitization effect of fluzoparib.?The underlying mechanisms involved increased apoptosis, cell-cycle arrest, enhanced irradiation-induced DNA damage, and delayed DNA-damage repair.
  • In Vitro
    Fluzoparib (30μM; 24 hour) increases the levels of γH2AX in a concentration‐dependent manner in both BRCA2‐deficient V‐C8 cells and?BRCA1‐deficient MDA‐MB‐436 cells, but not in BRCA‐proficient V‐C8#13‐5 cells.Fluzoparib (10?μM; 24 hour) increases levels of both pCDK1 and cyclin B, indicating activation of the G2/M checkpoint in MDA‐MB‐436 cells.Fluzoparib (10μM; 72 hour) increases the processing of caspase‐3, ‐8, and ‐9 concentration‐dependently, it induces G2/M arrest and apoptosis in HR‐deficient MDA‐MB‐436 cellscells.Fluzoparib is preferentially efficacious against HR‐deficient cells, such as BRCA1‐deficient (UWB1.289), MDA‐MB‐436, BRCA2‐deficient (V‐C8), BRCA1‐deficientBRCA2‐mutated (MX‐1) and BRCA1 hypermethylated (OVCAR‐8) cells with IC50 values of 0.51μM, 1.57?μM, 0.053 μM, 1.57μM, and 1.43μM, respectively. The IC50 values for HR‐proficient cells (V‐C8#13‐5 and UWB1.289 BRCA1) are both >10μM.
  • In Vivo
    Fluzoparib (oral gavage; 0.3, 1, or 3mg/kg; single dose) exhibits a good pharmacokinetic profile in Female Balb/cA nude mice (5‐6 weeks old) mice bearing MDA‐MB‐436. After a single oral dose, fluzoparib is rapidly absorbed and rapidly cleared from blood at all dose levels; plasma concentrations of fluzoparib quickly reaches maximum within 2hours. In contrast, concentrations of fluzoparib in tumor remains at high levels even at 24 hours after dosing (57.9ng/g , 39.3 ng/g, and 85.6ng/g for doses of 0.3, 1, and 3mg/kg, respectively).Fluzoparib (oral gavage; 30 mg/kg; 21 days) apparently inhibits the growth of tumor with an inhibition rate of 59% (day 21) at 30mg/kg, and it does not cause significant loss of body weight in Nude mice bearing MDA‐MB‐436 (BRCA1‐deficient)model.Fluzoparib (3mg/kg) combines with Cisplatin, Paclitaxel, or Apatinib (oral gavage; BID; 21 days) causes growth inhibition with rates of 61.4%, 55.3%, and 72.8%, respectively.Fluzoparib, Cisplatin, and Apatinib combination or Fluzoparib, Paclitaxel, and Apatinib combination can cause growth inhibition with rates of 84.9% and 75.6% (day 21), respectively in vivo.The 2‐drug combination of Fluzoparib with cisplatin and The 3‐drug Fluzoparib, Cisplatin, and Apatinib combination lead to loss of body weight, whereas no apparent toxicity was observed in other combinations.
  • Synonyms
    SHR3162, HS10160
  • Pathway
    Cell Cycle/DNA Damage
  • Target
    PARP
  • Recptor
    PARP
  • Research Area
    ——
  • Indication
    ——

Chemical Information

  • CAS Number
    1358715-18-0
  • Formula Weight
    472.4
  • Molecular Formula
    C22H16F4N6O2
  • Purity
    >98% (HPLC)
  • Solubility
    DMSO:94 mg/mL (198.98 mM)
  • SMILES
    C1CN2C(=NC(=N2)C(F)(F)F)CN1C(=O)C3=C(C=CC(=C3)CC4=NNC(=O)C5=CC=CC=C54)F
  • Chemical Name
    ——

Shipping & Storage Information

  • Storage
    (-20℃)
  • Shipping
    With Ice Pack
  • Stability
    ≥ 2 years

Reference

1. Wang L , Yang C , Xie C , et al. Pharmacologic characterization of fluzoparib, a novel poly(ADP‐ribose) polymerase inhibitor undergoing clinical trials[J]. Cancer Science, 2019.
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