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Bimiralisib(PQR309)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Bimiralisib(PQR309)图片
CAS NO:1225037-39-7
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 411.38
Formula C17H20F3N7O2
CAS No. 1225037-39-7(free base);
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 10 mM in DMSO
Water: N/A
Ethanol: N/A
SMILES Code NC1=NC=C(C2=NC(N3CCOCC3)=NC(N4CCOCC4)=N2)C(C(F)(F)F)=C1
Synonyms Bimiralisib; PQR309; PQR-309; PQR309; PI3K-IN-2; PI3K IN-2
实验参考方法
In Vitro

In vitro activity: PQR309 (also known as Bimiralisib) is a potent, brain-penetrant, orally bioavailable, balanced pan-inhibitor of PI3K/mTOR (phosphoinositide-3-kinase/mammalian target of rapamycin) with IC50s of 33 nM, 451 nM, 661 nM, 708 nM and 89 nM for PI3Kα, PI3Kδ, PI3Kβ, PI3Kγ and mTOR, respectively. Bimiralisib has potential antineoplastic activity and is orally available, crosses the blood-brain barrier, and displayed favorable pharmacokinetic parameters in mice, rats, and dogs. Bimiralisib demonstrated efficiency in inhibiting proliferation in tumor cell lines and a rat xenograft model. Bimiralisib has a broad application range in oncology, including treatment of brain tumors or CNS metastasis. Bimiralisib is currently in phase II clinical trials for advanced solid tumors and refractory lymphoma.


Kinase Assay: QR309 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.


Cell Assay: 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.

In VivoOral 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 5='' 10='' 14='' h='' after='' which='' reflects='' the='' time='' point='' when='' drug='' reaches='' median='' gi50='' determined='' in='' tumor='' cell='' lines.='' female='' rats='' a='' single='' oral='' dose='' achieves='' similar='' levels='' as='' intravenous='' injection='' with='' regard='' to='' cmax.='' half-life='' of='' 5-8='' and='' an='' auc0.25-12='' around='' 000='' ml='' contributed='' excellent='' bioavailability='' 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.
Animal modelMale nude NIH rats bearing PC-3 tumors
Formulation & DosageDissolved in DMSO to 40 mg/mL. The solution is diluted with 20% HPBCD [(2-hydroxypropyl)-β-cyclodextrin] in water; 5, 10, 15 mg/kg; i.v.
ReferencesJ Med Chem. 2017 Sep 14;60(17):7524-7538; Eur J Cancer. 2018 Jun;96:6-16.