Bimiralisib (PQR309) - 98%, high purity , CAS No.1225037-39-7, Inhibitor of mechanistic target of rapamycin kinase;Inhibitor of phosphatidylinositol-4;5-bisphosphate 3-kinase catalytic subunit alpha;Inhibitor of phosphatidylinositol-4;5-bisphosphate 3-kinase catalytic subunit beta;Inhibitor of phosphatidylinositol-4;

Item Number

B414146

• Synonyms: AS-49856 | GTPL8383 | UNII-6Z3QHB00LB | PQR309; Bimiralisib free base | s8738 | BCP15887 | PQR 309 | Q27088437 | 5-(4,6-Di-4-morpholinyl-1,3,5-triazin-2-yl)-4-(trifluoromethyl)-2-pyridinamine | NSC785117 | NSC-785117 | A3W | Bimiralisib [USAN:INN:WHO-DD]
• Specifications & Purity: Moligand™, ≥98%
• Biochemical and Physiological Mechanisms: Bimiralisib (PQR309) is a novel brain-penetrant dual PI3K/mTOR inhibitor with in vitro and in vivo antilymphoma activity. It displays excellent selectivity versus PI3K-related lipid kinases, protein kinases and unrelated targets.
• Storage Temp: Store at -20°C
• Shipped In: Ice chest + Ice pads
• Grade: Moligand™
• Action Type: INHIBITOR
• Mechanism of action: Inhibitor of mechanistic target of rapamycin kinase;Inhibitor of phosphatidylinositol-4;5-bisphosphate 3-kinase catalytic subunit alpha;Inhibitor of phosphatidylinositol-4;5-bisphosphate 3-kinase catalytic subunit beta;Inhibitor of phosphatidylinositol-4

Product Description

Information

Bimiralisib (PQR309) is a novel brain-penetrant dualPI3K/mTORinhibitor with in vitro and in vivo antilymphoma activity. It displays excellent selectivity versus PI3K-related lipid kinases, protein kinases and unrelated targets.

Targets

PI3Kα (Cell-free assay); PI3Kβ (Cell-free assay); mTOR (Cell-free assay); PI3Kγ (Cell-free assay); PI3Kδ (Cell-free assay) 1.5 nM(Kd); 11 nM(Kd); 12 nM(Kd); 25 nM(Kd); 25 nM(Kd)

In vitro

PQR309 shows in vitro activity with a median IC50 value of 233 nmol/L (95% CI, 174-324 nmol/L) in most of the tesed lymphoma cell lines (increasing doses, 72 hours). The arrest in proliferation is mainly due to cell cycle arrest with a block in G1 rather than to apoptosis, limited to only 2/7 cell lines. PQR309 is more active in B-cell lymphoma cell lines (DLBCL, MCL, CLL, and SMZL) than in the T-cell derived ALCL. PQR309 inhibits PI3K/mTOR signaling in lymphoma cell lines. It has in vitro and in vivo antilymphoma activity as single agent and in combination.\xa0

In vivo

PQR309 is orally available, crosses the blood−brain barrier, and displayed favorable pharmacokinetic parameters in mice, rats, and dogs. It shows little clearance when exposed to rat, dog, and human liver microsomes, with a quicker turnover of PQR309 in mouse liver microsomes, where 40% of the compound was eliminated within 30 min. In female mice, plasma concentrations of PQR309 depended on the drug administration route, resulting in half-lives of approximately 13-36 min for po administration vs 9-10 min for iv administration. PQR309 shows excellent oral bioavailability (>50%). Male Beagle dogs, exposed to PQR309 at 10 mg/kg po, showed maximal drug plasma concentrations Cmax of 583 ng/mL (approximately 1.5 μM) after 60-90 min and a half-life of >7 h, which results in drug levels of approximately 0.38 μM (150 ng/mL) after 24 h. The oral bioavailability in male Beagle dogs was estimated to be 23%. Altogether the PK studies in the three models (female CD-1 mouse, female Sprague-Dawley rats, male Beagle dog) show rapid absorption of PQR309 and good oral bioavailability. PQR309 demonstrates efficiency in inhibiting proliferation in tumor cell lines (PC3 prostate cancer cells) and a rat xenograft model (PC3 xenograft model).

Cell Research(from reference)

Cell lines：lymphoma cell lines 

Concentrations：500 nmol/L 

Incubation Time：72 h