Bimiralisib (PQR309)

Catalog No.S8738

For research use only.

Bimiralisib (PQR309) is a novel brain-penetrant dual PI3K/mTOR inhibitor with in vitro and in vivo antilymphoma activity. It displays excellent selectivity versus PI3K-related lipid kinases, protein kinases and unrelated targets.

Bimiralisib (PQR309) Chemical Structure

CAS No. 1225037-39-7

Selleck's Bimiralisib (PQR309) has been cited by 4 Publications

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Biological Activity

Description Bimiralisib (PQR309) is a novel brain-penetrant dual PI3K/mTOR inhibitor with in vitro and in vivo antilymphoma activity. It displays excellent selectivity versus PI3K-related lipid kinases, protein kinases and unrelated targets.
Targets
PI3Kα [2]
(Cell-free assay)
PI3Kβ [2]
(Cell-free assay)
mTOR [2]
(Cell-free assay)
PI3Kγ [2]
(Cell-free assay)
PI3Kδ [2]
(Cell-free assay)
1.5 nM(Kd) 11 nM(Kd) 12 nM(Kd) 25 nM(Kd) 25 nM(Kd)
In vitro

PQR309 shows in vitro activity with a median IC50 value of 233 nmol/L (95% CI, 174-324 nmol/L) in most of the tesed lymphoma cell lines (increasing doses, 72 hours). The arrest in proliferation is mainly due to cell cycle arrest with a block in G1 rather than to apoptosis, limited to only 2/7 cell lines. PQR309 is more active in B-cell lymphoma cell lines (DLBCL, MCL, CLL, and SMZL) than in the T-cell derived ALCL. PQR309 inhibits PI3K/mTOR signaling in lymphoma cell lines. It has in vitro and in vivo antilymphoma activity as single agent and in combination[1]

In vivo

PQR309 is orally available, crosses the blood−brain barrier, and displayed favorable pharmacokinetic parameters in mice, rats, and dogs. It shows little clearance when exposed to rat, dog, and human liver microsomes, with a quicker turnover of PQR309 in mouse liver microsomes, where 40% of the compound was eliminated within 30 min. In female mice, plasma concentrations of PQR309 depended on the drug administration route, resulting in half-lives of approximately 13-36 min for po administration vs 9-10 min for iv administration. PQR309 shows excellent oral bioavailability (>50%). Male Beagle dogs, exposed to PQR309 at 10 mg/kg po, showed maximal drug plasma concentrations Cmax of 583 ng/mL (approximately 1.5 μM) after 60-90 min and a half-life of >7 h, which results in drug levels of approximately 0.38 μM (150 ng/mL) after 24 h. The oral bioavailability in male Beagle dogs was estimated to be 23%. Altogether the PK studies in the three models (female CD-1 mouse, female Sprague-Dawley rats, male Beagle dog) show rapid absorption of PQR309 and good oral bioavailability. PQR309 demonstrates efficiency in inhibiting proliferation in tumor cell lines (PC3 prostate cancer cells) and a rat xenograft model (PC3 xenograft model)[2].

Protocol (from reference)

Cell Research:

[1]

  • Cell lines: lymphoma cell lines
  • Concentrations: 500 nmol/L
  • Incubation Time: 72 h
  • Method:

    --

Animal Research:

[2]

  • Animal Models: female CD-1 mice, female Sprague-Dawley rats, and male Beagle dogs
  • Dosages: 5 mg/kg (i.v) or 10 mg/kg (oral)
  • Administration: by either a single intravenous bolus or a single oral application

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 411.38
Formula

C17H20F3N7O2

CAS No. 1225037-39-7
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C1COCCN1C2=NC(=NC(=N2)C3=CN=C(C=C3C(F)(F)F)N)N4CCOCC4

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02483858 Completed Drug: PQR 309 Cancer PIQUR Therapeutics AG|Roswell Park Cancer Institute|M.D. Anderson Cancer Center|Mayo Clinic|Hospital Clinic of Barcelona|University College London Hospitals|Churchill Hospital|Case Western Reserve University|University Hospital Zürich March 21 2019 Phase 1
NCT03127020 Completed Drug: PQR309 Lymphoma|Non-Hodgkin Lymphoma PIQUR Therapeutics AG|University Hospital Basel Switzerland|University Hospital Munich|University Hospital Freiburg|Charite University Berlin Germany|University of Stuttgart June 2016 Phase 2
NCT02723877 Completed Drug: PQR309|Drug: Eribulin Metastatic Breast Cancer PIQUR Therapeutics AG|Hospital Universitario Ramon y Cajal|Hospital Universitari Vall d''Hebron Research Institute|Institut Català d''Oncologia|Churchill Hospital|Barts Cancer Institute|Fundación Instituto Valenciano de Oncología March 28 2016 Phase 1|Phase 2
NCT02850744 Terminated Drug: PQR309 Glioblastoma Multiforme PIQUR Therapeutics AG|University Hospital Basel Switzerland|University Hospital Inselspital Berne|University Hospital Zürich July 2015 Phase 2
NCT02249429 Completed Drug: bimiralisib Lymphoma Malignant PIQUR Therapeutics AG|University College London Hospitals|Churchill Hospital|Royal Marsden NHS Foundation Trust|University of Haifa|Weill Medical College of Cornell University|Institut Curie|University Clinical Center Sarajevo|Clinical Center Kragujevac|Clinical Center Nis Nis|Institute for Oncology and Radiology Serbia Belgrade|University Clinical Centre of Republic of Srpska May 2015 Phase 2

(data from https://clinicaltrials.gov, updated on 2022-08-01)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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