Bimiralisib (PQR309)

製品コードS8738 バッチS873802

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder
	化学式	C₁₇H₂₀F₃N₇O₂
	分子量	411.38	CAS No.	1225037-39-7
Solubility (25°C)*	体外


* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

生物活性

製品説明	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.
in vitro	Bimiralisib (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. It is more active in B-cell lymphoma cell lines (DLBCL, MCL, CLL, and SMZL) than in the T-cell derived ALCL. This compound inhibits PI3K/mTOR signaling in lymphoma cell lines. It has in vitro and in vivo antilymphoma activity as single agent and in combination.
in vivo	Bimiralisib (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 in mouse liver microsomes, where 40% of the compound was eliminated within 30 min. In female mice, plasma concentrations 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. This compound shows excellent oral bioavailability (>50%). Male Beagle dogs, exposed to it 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 and good oral bioavailability. It demonstrates efficiency in inhibiting proliferation in tumor cell lines (PC3 prostate cancer cells) and a rat xenograft model (PC3 xenograft model).

プロトコル(参考用のみ)

細胞アッセイ	細胞株	lymphoma cell lines
	濃度	500 nmol/L
	反応時間	72 h
	実験の流れ	--
動物実験	動物モデル	female CD-1 mice, female Sprague-Dawley rats, and male Beagle dogs
	投薬量	5 mg/kg (i.v) or 10 mg/kg (oral)
	投与方法	by either a single intravenous bolus or a single oral application

参考

https://pubmed.ncbi.nlm.nih.gov/29066507/
https://pubmed.ncbi.nlm.nih.gov/28829592/

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

PQR309, a dual PI3K/mTOR inhibitor, synergizes with gemcitabine by impairing the GSK-3β and STAT3/HSP60 signaling pathways to treat nasopharyngeal carcinoma [ Cell Death Dis, 2024, 15(3):237]	PubMed: 38555280
Resistance to PI3κδ inhibitors in marginal zone lymphoma can be reverted by targeting the IL-6/PDGFRA axis [ Haematologica, 2022, 10.3324/haematol.2021.279957]	PubMed: 35484662
Functional impact and targetability of PI3KCA, GNAS, and PTEN mutations in a spindle cell rhabdomyosarcoma with MYOD1 L122R mutation [ Cold Spring Harb Mol Case Stud, 2022, 8(1)a006140]	PubMed: 35012940
Synergism between the phosphatidylinositol 3-kinase p110β isoform inhibitor AZD6482 and the mixed lineage kinase 3 inhibitor URMC-099 on the blockade of glioblastoma cell motility and focal adhesion formation [ Cancer Cell Int, 2021, 21(1):24]	PubMed: 33407478
PI3K/mTORC1/2 inhibitor PQR309 inhibits proliferation and induces apoptosis in human glioblastoma cells. [ Oncol Rep, 2020, 43(3):773-782]	PubMed: 32020210

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。