Catalog Number
ACM1225037397
Product Name
Bimiralisib free base
Description
Bimiralisib, also known as PQR309, is an orally bioavailable pan inhibitor of phosphoinositide-3-kinases (PI3K) and inhibitor of the mammalian target of rapamycin (mTOR), with potential antineoplastic activity. PI3K/mTOR kinase inhibitor PQR309 inhibits the PI3K kinase isoforms alpha, beta, gamma and delta and, to a lesser extent, mTOR kinase, which may result in tumor cell apoptosis and growth inhibition in cells overexpressing PI3K/mTOR. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to both chemotherapy and radiotherapy.
Synonyms
PQR309; PQR-309; PQR309; Bimiralisib free base
IUPAC Name
5-(4,6-dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine
Molecular Formula
C17H20F3N7O2
Canonical SMILES
NC1=NC=C(C2=NC(N3CCOCC3)=NC(N4CCOCC4)=N2)C(C(F)(F)F)=C1
InChI
InChI=1S/C17H20F3N7O2/c18-17(19,20)12-9-13(21)22-10-11(12)14-23-15(26-1-5-28-6-2-26)25-16(24-14)27-3-7-29-8-4-27/h9-10H,1-8H2,(H2,21,22)
InChI Key
ADGGYDAFIHSYFI-UHFFFAOYSA-N
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Storage
Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
Alternative CAS
1820902-72-4 (HCl salt); 1225037-39-7 (free base)
Biological Target
Bimiralisib (PQR309) is a brain-penetrant, 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.
Drug Formulation
This drug may be formulated in DMSO
Elemental Analysis
C, 49.63; H, 4.90; F, 13.85; N, 23.83; O, 7.78
HS Tariff Code
2934.99.9001
In Vitro Activity
The results of a CCK-8 assay revealed a significant suppressive effect of PQR309 on U87 and U251 cells. The results indicated that the viability of the cells was significantly (P<0.05) suppressed in a dose- and time-dependent manner after the cells were treated with PQR309 (0, 1, 5, 10, 50 and 100 µM) after 72 h (Fig. 1B). The colony formation rates of treated U87 and U251 cells decreased in various concentration groups compared to the control (Fig. 1C-D). According to these results, the IC50 values of PQR309 were 7.104 (95% CI, 5.6-8.5) and 11.986 (95% CI, 10.6-13.4) in U87 and U251 cells, respectively.
Reference: Oncol Rep. 2020 Mar; 43(3): 773-782. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040887/
In Vivo Activity
Rats were injected with 2 × 107 human PC3 prostate cancer cells into one flank and randomized after 16 days. From day 17 the control group received vehicle once daily. Compound 1 (bimiralisib) was orally administered at 5 mg/kg, 10 mg/kg (both daily, QD), or 15 mg/kg [5 consecutive days, 2 days off drug (QD × 5, 2 days off)] for 28 days to match the timelines of regulatory toxicology studies. Treatment with 1 led to significant tumor size reductions: tumor growth was inhibited dose-dependently (best T/C of 31-12%, Figure 6A). Compound 1 was best tolerated at 5 mg/kg without significant body weight changes (Figure 6B). At 10 mg/kg, 1 caused a reduction of body weight, which accumulated to a reduction of 15% after 28 days of treatment. Similarly, 15 mg/kg of 1 led to body weight loss after 5 days of treatment, which was reversible during the recovery period. After 28 days of drug exposure (day 44 of the experiment), animals with body weight loss fully recovered within a treatment-free period (days 45-50) without overt signs of tumor cell proliferation. In a subsequent treatment period tumor growth remained inhibited and body weight loss was only observed in the 15 mg/kg group.
Reference: J Med Chem. 2017 Sep 14; 60(17): 7524-7538. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656176/
Shipping
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Stock Solution Storage
0-4 °C for short term (days to weeks), or -20 °C for long term (months).
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