PQR-309

PQR-309 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 PQR-309 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.

Product information

CAS Number: 1225037-39-7

Molecular Weight: 411.38

Formula: C17H20F3N7O2

Synonym:

Bimiralisib free base

PQR309

PQR-309

Related CAS Number:

1820902-72-4 (HCl)

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

Smiles: NC1=CC(=C(C=N1)C1N=C(N=C(N=1)N1CCOCC1)N1CCOCC1)C(F)(F)F

InChiKey: ADGGYDAFIHSYFI-UHFFFAOYSA-N

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)

Technical Data

Appearance: Solid Power.

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

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

PQR-309 is a highly selective pan-PI3K inhibitor with a balanced targeting of mTOR kinase. PQR-309 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 PQR-309 in brain and plasma samples illustrates that PQR-309 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 PQR-309 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 PQR-309 (>50%). Twenty-four hours after po administration, plasma levels of PQR-309 are still >2 μM (800-1000 ng/mL). Moreover, after 1-2 h exposure to PQR-309 , drug levels in rat brain samples are comparable to plasma levels, confirming rapid access of PQR-309 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.