Samotolisib (LY3023414)

製品コードS8322 バッチS832202

印刷

化学情報

Chemical Structure Synonyms GTPL8918 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C23H26N4O3
分子量 406.48 CAS No. 1386874-06-1
Solubility (25°C)* 体外 DMSO 81 mg/mL (199.27 mM)
Ethanol 40 mg/mL (98.4 mM)
Water Insoluble
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 LY3023414 (Samotolisib, GTPL8918) is an oral ATP competitive inhibitor of the class I PI3K isoforms, mTOR and DNA-PK.
in vitro LY3023414 shows high solubility across a wide pH range. In vitro, inhibition of PI3K/AKT/mTOR signaling by LY3023414 causes G1 cell-cycle arrest and resulted in broad antiproliferative activity in cancer cell panel screens. In cell-based assays, LY3023414 inhibition of PI3K and mTOR is assessed in the PTEN-deficient U87 MG glioblastoma cell line. LY3023414 inhibits the phosphorylation of AKT at position T308 downstream of PI3K at an IC50 of 106 nM. Similarly, LY3023414 inhibits phosphorylation of AKT at position S473 (IC50 = 94.2 nM) by mTORC2 as well as phosphorylation of mTORC1 kinase targets p70S6K (position T389; IC50 =10.6 nM) and 4E-BP1 (positions T37/46; IC50 = 187 nM). The downstream phosphorylation of S6RP at positions pS240/244 (IC50 = 19.1 nM) by p70S6K was inhibited as well, indicating target inhibition along the entire PI3K/AKT/mTOR pathway by LY3023414[1].
in vivo In vivo, LY3023414 demonstrates high bioavailability and dose-dependent dephosphorylation of PI3K/AKT/mTOR pathway downstream substrates such as AKT, S6K, S6RP, and 4E-BP1 for 4 to 6 hours, reflecting the drug's half-life of 2 hours. Intermittent target inhibition is sufficient for its antitumor activity. LY3023414 shows time- and dose-dependent target inhibition in vivo. It is currently being evaluated in phase 1 and 2 trials for the treatment of human malignancies[1].

プロトコル(参考用のみ)

動物実験 動物モデル athymic nude, CD-1 nude and NMRI athymic nude mice(Xenograft tumors)
投薬量 --
投与方法 p.o.

カスタマーフィードバック

Data from [Data independently produced by , , Oncotarget, 2017, 8(58): 98964-98973]

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：

Protective effect of leukemia inhibitory factor on the retinal injury induced by acute ocular hypertension in rats [ Exp Ther Med, 2023, 25(1):19] PubMed: 36561619
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
Microenvironment drives cell state, plasticity, and drug response in pancreatic cancer [ Cell, 2021, 184(25):6119-6137.e26] PubMed: 34890551
Samotolisib Attenuates Acute Liver Injury Through Inhibiting Caspase-11-Mediated Pyroptosis Via Regulating E3 Ubiquitin Ligase Nedd4 [ Front Pharmacol, 2021, 12:726198] PubMed: 34483936
Uraemic extracellular vesicles augment osteogenic transdifferentiation of vascular smooth muscle cells via enhanced AKT signalling and PiT-1 expression [ J Cell Mol Med, 2021, 25(12):5602-5614] PubMed: 33960650
LY3023414 inhibits both osteogenesis and osteoclastogenesis through the PI3K/Akt/GSK3 signalling pathway [ Bone Joint Res, 2021, 10(4):237-249] PubMed: 33789427
Phosphorylation of PRAS40 contributes to the activation of the PI3K/AKT/mTOR signaling pathway and the inhibition of autophagy following status epilepticus in rats [ Exp Ther Med, 2020, 20(4):3625-3632] PubMed: 32855714
Autophagy inhibition sensitizes LY3023414-induced anti-glioma cell activity in vitro and in vivo. [ Oncotarget, 2017, 8(58):98964-98973] PubMed: 29228741

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。