Zimlovisertib (PF-06650833)

製品コードS8531 バッチS853102

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder

化学式

C₁₈H₂₀FN₃O₄

分子量

361.37

CAS No.

1817626-54-2

Solubility (25°C)*

体外

DMSO

72 mg/mL (199.24 mM)

Ethanol

4 mg/mL (11.06 mM)

Water

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	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O 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。	3.600mg/ml (9.96mM)	Taking the 1 mL working solution as an example, add 50 μL of 72 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil 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。	0.900mg/ml (2.49mM)	Taking the 1 mL working solution as an example, add 50 μL of 18 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. 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	Zimlovisertib (PF-06650833) は、IC50が0.2 nMである強力かつ選択的なIRAK4阻害剤です。
in vitro	Zimlovisertib (PF-06650833) was assessed in a panel of 278 kinases (Invitrogen) at 200 nM inhibitor concentration using the ATP Km for each kinase, revealing its kinome selectivity profile. Approximately 100% inhibition was observed for IRAK4, while greater than 70% inhibition was seen for the following kinases, in order of potency: IRAK1, MNK2, LRRK2, CLK4, and CK1γ1. This compound was subsequently evaluated in a whole cell functional VEGF2R assay (PAE-KDR cell line), where no activity was observed at concentrations up to and including 30 μM. .
in vivo	Zimlovisertib (PF-06650833) significantly inhibits LPS-induced TNF in a dose dependent manner. Mean exposures of this compound in plasma are 2.1 nM, 7.7 nM, 19 nM and 150 nM free, respectively, at 2.5 hours after oral administration at 0.3 mg/kg, 1 mg/kg, 3 mg/kg and 30 mg/kg. The fraction unbound in rat plasma of PF-06650833 is 0.3.

プロトコル(参考用のみ)

動物実験	動物モデル	Male Sprague Dawley rats
	投薬量	0.1 mg/kg, 1 mg/kg, 3 mg/kg, 30 mg/kg
	投与方法	Oral

参考

https://pubmed.ncbi.nlm.nih.gov/28498658-discovery-of-clinical-candidate-1-2s3s4s-3-ethyl-4-fluoro-5-oxopyrrolidin-2-ylmethoxy-7-methoxyisoquinoline-6-carboxamide-pf-06650833-a-potent-selective-inhibitor-of-interleukin-1-receptor-associated-kinase-4-irak4-by-fragment-based-drug-design/?from_single_result=Discovery+of+Clinical+Candidate+1-%7B%5B%282S%2C3S%2C4S%29-3-Ethyl-4-fluoro-5-oxopyrrolidin-2-yl%5Dmethoxy%7D-7-methoxyisoquinoline-6-carboxamide+%28PF-06650833%29%2C+a+Potent%2C+Selective+Inhibitor+of+Interleukin-1+Receptor+Associated+Kinase+4+%28IRAK4%29%2C+by+Fragment-Based+Drug+Design.

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：

Targeting IL-1/IRAK1/4 signaling in Acute Myeloid Leukemia Stem Cells Following Treatment and Relapse [ bioRxiv, 2024, 2024.11.09.622796]	PubMed: 39605740
IRAK1 inhibition blocks the HIV-1 RNA mediated pro-inflammatory cytokine response from microglia [ J Gen Virol, 2023, 104(5)001858]	PubMed: 37256770
A temperature-regulated circuit for feeding behavior [ Nat Commun, 2022, 13(1):4229]	PubMed: 35869064
Pacritinib Inhibition of IRAK1 Blocks Aberrant TLR8 Signalling by SARS-CoV-2 and HIV-1-Derived RNA [ J Innate Immun, 2022, 1-11]	PubMed: 35785771
Inhibition of IRAK1/4 enhances the antitumor effect of lenvatinib in anaplastic thyroid cancer cells [ Cancer Sci, 2021, 112(11):4711-4721]	PubMed: 34328666
A temperature-regulated circuit for feeding behavior [ Research Square, 2021, 10.21203/rs.3.rs-916525/v1]	PubMed: None

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。