Bimiralisib (PQR309)

Catalog No.S8738 Batch:S873802

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Technical Data

Formula

C17H20F3N7O2
Molecular Weight 411.38 CAS No. 1225037-39-7
Solubility (25°C)* In vitro  
 
 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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 Assay:

[1]
  • Cell lines

    lymphoma cell lines

  • Concentrations

    500 nmol/L

  • Incubation Time

    72 h

  • Method

    --
Animal Study:

[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

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

Resistance to PI3κδ inhibitors in marginal zone lymphoma can be reverted by targeting the IL-6/PDGFRA axis [ Haematologica, 2022, 10.3324/haematol.2021.279957] PubMed: 35484662
Functional impact and targetability of PI3KCA, GNAS, and PTEN mutations in a spindle cell rhabdomyosarcoma with MYOD1 L122R mutation [ Cold Spring Harb Mol Case Stud, 2022, 8(1)a006140] PubMed: 35012940
Synergism between the phosphatidylinositol 3-kinase p110β isoform inhibitor AZD6482 and the mixed lineage kinase 3 inhibitor URMC-099 on the blockade of glioblastoma cell motility and focal adhesion formation [ Cancer Cell Int, 2021, 21(1):24] PubMed: 33407478
PI3K/mTORC1/2 inhibitor PQR309 inhibits proliferation and induces apoptosis in human glioblastoma cells. [ Oncol Rep, 2020, 43(3):773-782] PubMed: 32020210

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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