Bimiralisib free base

Cas：1225037-39-7 (free base)

Product Information：

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.

Chemical Formula: C17H20F3N7O2

Exact Mass: 411.1631

Molecular Weight: 411.3892

Elemental Analysis: C, 49.63; H, 4.90; F, 13.85; N, 23.83; O, 7.78

Synonym: 

PQR309

PQR-309

PQR309

Bimiralisib free base

Chemical Name: 5-(4,6-dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine

InChi Key:

ADGGYDAFIHSYFI-UHFFFAOYSA-N

InChi Code: 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)

Smiles Code:

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

Technical Data：

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: 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.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

In Vitro：

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

In Vivo：

Oral administration yields similar concentrations of Bimiralisib in brain and plasma samples illustrates that Bimiralisib 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.

References：

1. Big Hopes with Small Molecules - PIQUR Therapeutics AG is aiming to Turn Cancer into a Manageable Disease. Chimia (Aarau). 2014 Dec;68(12):891-2. doi: 10.2533/chimia.2014.891. PubMed PMID: 26508614.

Products are for research use only. Not for human use.