1. PI3K/Akt/mTOR
  2. PI3K
    mTOR

PQR309 (Synonyms: Bimiralisib)

Cat. No.: HY-12868 Purity: 99.43%
Handling Instructions

PQR309 is a potent, brain-penetrant, orally bioavailable, pan-class I PI3K/mTOR inhibitor with IC50s of 33 nM, 451 nM, 661 nM, 708 nM and 89 nM for PI3Kα, PI3Kδ, PI3Kβ, PI3Kγ and mTOR, respectively.

For research use only. We do not sell to patients.
PQR309 Chemical Structure

PQR309 Chemical Structure

CAS No. : 1225037-39-7

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 109 In-stock
2 mg USD 72 In-stock
5 mg USD 120 In-stock
10 mg USD 168 In-stock
50 mg USD 528 In-stock
100 mg USD 888 In-stock
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  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

PQR309 is a potent, brain-penetrant, orally bioavailable, pan-class I PI3K/mTOR inhibitor with IC50s of 33 nM, 451 nM, 661 nM, 708 nM and 89 nM for PI3Kα, PI3Kδ, PI3Kβ, PI3Kγ and mTOR, respectively.

IC50 & Target

IC50: 33 nM (PI3Kα), 451 nM (PI3Kδ), 661 nM (PI3Kβ), 708 nM (PI3Kγ), 36 nM (PI3Kα-H1047R), 63 nM (PI3Kα-E542K), 136 nM (PI3Kα-E545K), 89 nM (mTOR)[1]

In Vitro

PQR309 is a highly selective pan-PI3K inhibitor with a balanced targeting of mTOR kinase. PQR309 also inhibits PI3Kα-H1047R), PI3Kα-E542K and PI3Kα-E545K with IC50s of 36 nM, 63 nM and 136 nM, respectively[1].

In Vivo

Oral administration yields similar concentrations of PQR309 in brain and plasma samples illustrates that PQR309 readily passes the blood–brain barrier. In mice, both po and iv application routes show a rapid drop below 200 ng/mL (~0.5 μM) of PQR309 within <1 h (iv) to <2 h (po) after administration, which reflects the time point when the drug reaches the median GI50 determined in tumor cell lines. In female rats a single oral dose (10 mg/kg) achieves similar drug levels as a single intravenous injection (5 mg/kg) with regard to Cmax. The half-life of 5-8 h and an AUC0.25-12 of around 14 000 h•ng/mL contributed to an excellent oral bioavailability of PQR309 (>50%). Twenty-four hours after po administration, plasma levels of PQR309 are still >2 μM (800-1000 ng/mL). Moreover, after 1-2 h exposure to PQR309, drug levels in rat brain samples are comparable to plasma levels, confirming rapid access of PQR309 to the brain[1].

Clinical Trial
References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 2.4308 mL 12.1542 mL 24.3084 mL
5 mM 0.4862 mL 2.4308 mL 4.8617 mL
10 mM 0.2431 mL 1.2154 mL 2.4308 mL
Please refer to the solubility information to select the appropriate solvent.
Cell Assay
[1]

Human tumor cell lines are seeded into 96-well microtiter plates and exposed to five (1/2 log serial) drug dilutions plus control, followed by 48 h (except for two controls of each cell line which are fixed with TCA (cell population at t =0 h [Tz]). The assay is terminated by fixation with TCA (10% final). Cell density is determined using a sulforhodamine B staining protocol and the absorbance measured at 515 nm. Using seven absorbance measurements, the percentage growth is calculated at each of the drug concentrations levels. Percentage growth inhibition is calculated. The NTRC Oncolines 44 cell lines are exposed for 72 h to 9-point 3-fold serial dilutions of PQR309. The concentration of 50% growth inhibition is associated with the signal ((luminescenceuntreated,t=72h-luminescencet=0)/2)+luminescencet=0. The data set integrated here is used for IC50 calculations. IC50 values of A2058 or SKOV3 cell proliferation given are determined and calculated[1].
MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

PQR309 is dissolved in DMSO to 40 mg/mL. This solution is diluted with 20% HPBCD [(2-hydroxypropyl)-β-cyclodextrin] in water[1].

Mice[1]
Healthy male nude NIH rats are used. 2×107 PC-3 cells are injected subcutaneously at day 0 (D0) in 200 μL of RPMI1640 into the right flank of male nude rats, 24 h after a whole-body irradiation with a γ-source (5 Gy, 60Co). Tumor-bearing rats are randomized on day 16 (mean volume of 330±70 mm3 according to their individual tumor volume into five groups of each eight animals using Vivo manager software. Analysis of variance is performed to test for homogeneity between groups. Daily administration on D17-D44 and from D51 to D57: group 1, vehicle; group 2, compound 1 at 5 mg/kg; group 3, PQR309 at 10 mg/kg. Group 4: PQR309 at 15 mg/kg from D17 to D21, from D24 to D28, from D34 to D38, from D41 to D4, and from D51 to D56. Group 5: one iv injection of Vinorelbine at 2.5 mg/kg on D17, D24, D31, and D38. Final termination of rats is performed on D87. Body weight is measured at least twice a week. Length and width of tumors are measured and recorded twice a week with calipers, and the tumor volume is estimated.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

411.38

Formula

C₁₇H₂₀F₃N₇O₂

CAS No.

1225037-39-7

SMILES

NC1=NC=C(C2=NC(N3CCOCC3)=NC(N4CCOCC4)=N2)C(C(F)(F)F)=C1

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

10 mM in DMSO

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

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PQR309
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