Home PI3K/Akt/mTOR PI3K inhibitor - mTOR inhibitor Bimiralisib (PQR309) For research use only.

Bimiralisib (PQR309)

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

Bimiralisib (PQR309) Chemical Structure

CAS No. 1225037-39-7

Purity & Quality Control

Bimiralisib (PQR309) Related Products

Signaling Pathway

PI3K Signaling Pathways

PI3K Signaling Pathway

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
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]. 
Cell Research Cell lines lymphoma cell lines
Concentrations 500 nmol/L
Incubation Time 72 h
Method

--
In Vivo
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].
Animal Research 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
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02483858 Completed
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
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
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
Glioblastoma Multiforme
PIQUR Therapeutics AG|University Hospital Basel Switzerland|Insel Gruppe AG University Hospital Bern|University Hospital Zürich
 July 2015 Phase 2
NCT02249429 Completed
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

Chemical Information & Solubility

Molecular Weight 411.38 Formula

C17H20F3N7O2
CAS No. 1225037-39-7 SDF --
Smiles C1COCCN1C2=NC(=NC(=N2)C3=CN=C(C=C3C(F)(F)F)N)N4CCOCC4
Storage (From the date of receipt) 3 years -20°C powder

In vitro
Batch:

DMSO : 6 mg/mL ( (14.58 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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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.

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