PRT-060318 2HCl

製品コードS7738 バッチS773801

印刷

化学情報

Chemical Structure Synonyms PRT318 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C18H24N6O.2HCl
分子量 413.34 CAS No. 1194961-19-7(freebase)
Solubility (25°C)* 体外 DMSO 75 mg/mL (181.44 mM)
Water 75 mg/mL (181.44 mM)
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
water

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 75.000mg/ml (181.45mM) Taking the 1 mL working solution as an example, add 75 mg of this product to 1 ml of ddH2O, mix evenly to make it clear, The mixed solution should be used immediately for optimal results. 
* <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 PRT-060318（PRT318）は、HIT治療へのアプローチとして開発された、Sykチロシンキナーゼの新規選択的阻害剤です。
in vitro PRT318 inhibits platelet activation via GPVI/FcRγ, an ITAM receptor complex, but not via ADP or thrombin, which are G-protein coupled receptors. PRT318 effectively antagonizes CLL(chronic lymphocytic leukemia) cell survival after BCR triggering and in nurse-like cell-co-cultures. PRT318 inhibits Syk and extracellular signal-regulated kinase phosphorylation after BCR triggering.
in vivo In both rabbit and pig models, intravenous infusion of PRT060318 targets maximal inhibition of Syk kinase activity and significantly inhibits arterial thrombosis. The antithrombotic activity of PRT060318 in pigs is remarkable because it was achieved with complete inhibition of CVXN-induced platelet aggregation, with no effect on ADP-induced platelet aggregation, and no prolongation of ear bleeding time. Also, Syk inhibitor PRT318 is an active agent in HIT. Inhibition of Syk signaling with the orally bio-available PRT318 limits the thrombocytopenic and thrombotic effects of HIT IC in vivo.

プロトコル(参考用のみ)

細胞アッセイ 細胞株 LY3，LY4，LY7,LY18 cell lines
濃度 0-3μM
反応時間 0-72h
実験の流れ

The numbers of cells treated with various doses of PRT318 are followed over time. PRT318 inhibits growth of the sensitive cell lines in a dose-dependent manner. Two sensitive (LY7 and LY18) and 2 resistant (LY3 and LY4) cell lines are treated with indicated doses of PRT318.
動物実験 動物モデル C57Bl/6 Mice; transgenic HIT mice
投薬量 30 mg/kg
投与方法 orally via gavage

参考

  • http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3568699/
  • https://pubmed.ncbi.nlm.nih.gov/22362000/
  • https://pubmed.ncbi.nlm.nih.gov/21881044/
  • https://pubmed.ncbi.nlm.nih.gov/22025527/

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：

Small molecule activators of TAK1 promotes its activity-dependent ubiquitination and TRAIL-mediated tumor cell death [ Proceedings of the National Academy of Sciences, September 26, 2023, e2308079120] PubMed: 37733743
The protein segregase VCP/p97 promotes host antifungal defense via regulation of SYK activation [ PLOS Pathogens, October 29, 2024, e1012674] PubMed: 39471181
Physiological platelet aggregation assay to mitigate drug-induced thrombocytopenia using a microphysiological system [ Scientific Reports, June 5, 2024, 14(1)] PubMed: 38898080
Platelet spleen tyrosine kinase is a key regulator of anti-PF4 antibody-induced immunothrombosis [ Blood Advances, 2025, 1772-1785] PubMed: 39705541
Spleen tyrosine kinase inhibitors disrupt human neutrophil swarming and antifungal functions [ Microbiol Spectr, 2025, 13(1):e0254921] PubMed: 39601545
Guided monocyte fate to FRβ/CD163+ S1 macrophage antagonises atopic dermatitis via fibroblastic matrices in mouse hypodermis [ Cellular and Molecular Life Sciences, 2024, 14] PubMed: 39720957
Guided monocyte fate to FRβ/CD163+ S1 macrophage antagonises atopic dermatitis via fibroblastic matrices in mouse hypodermis [ Cell Mol Life Sci, 2024, 82(1):14] PubMed: 39720957
Multi-phased Kinetics and Interaction of Protein Kinase Signaling in Glycoprotein VI-Induced Platelet αIIbβ3 Integrin Activation and Degranulation [ Thrombosis and Haemostasis, 2024, 470-483] PubMed: 38653482
The protein segregase VCP/p97 promotes host antifungal defense via regulation of SYK activation [ PLoS Pathog, 2024, 20(10):e1012674] PubMed: 39471181
Multi-phased Kinetics and Interaction of Protein Kinase Signaling in Glycoprotein VI-Induced Platelet αIIbβ3 Integrin Activation and Degranulation [ Thromb Haemost, 2024, 10.1055/a-2311-0117] PubMed: 38653482

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。

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