CRT0066101 dihydrochloride

製品コードS8366 バッチS836603

印刷

化学情報

Synonyms

CRT0066101 2HCl

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₁₈H₂₂N₆O.2HCl

分子量

411.33

CAS No.

1883545-60-5

Solubility (25°C)*

体外

DMSO (warmed with 50ºC water bath)

82 mg/mL (199.35 mM)

Water

Insoluble

Ethanol

Insoluble

体内（毎回新しく調製した物を用意してください）

Clear solution	5% DMSO 1 95% Corn oil	0.5mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 10 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.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	4.1mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 82 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.

* <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	CRT0066101 dihydrochloride is a small molecule PKD family specific inhibitor which specifically blocks PKD1/2 activity and does not suppress PKCα/PKCβ/PKCε activity in multiple.
in vitro	CRT0066101 reduces BrdU incorporation, increases apoptosis, blocks neurotensin (NT)-induced PKD1/2 activation, reduces NT-induced PKD-mediated Hsp27 phosphorylation, attenuates PKD1-mediated NF-κB activation, and abrogates expression of NF-κB-dependent-dependent proliferative and pro-survival proteins. CRT0066101 significantly inhibits Panc-1 cell proliferation with an IC50 value of 1 μM. It also significantly reduces cell proliferation of Colo357, Panc-1, MiaPaCa-2, and AsPC-1 cells but has a modest effect in Capan-2 cells. Thus, CRT0066101 significantly blocks proliferation of PaCa cells that express moderate to high endogenous levels of PKD1/2. CRT0066101 (5 µM) blocks both the basal and NT-induced pS916-PKD1/2 (activated PKD1/2) in Panc-1 and Panc-28 cells, also abrogates NT-induced phosphorylation of Hsp27 (pS82-Hsp27), which is a physiological substrate of PKD1/2 in a dose-dependent manner^[1].
in vivo	CRT0066101 given orally (80 mg/kg/day) for 28 days significantly abrogates PaCa growth in Panc-1 subcutaneous xenograft model. Activated PKD1/2 expression in the treated tumor-explants is significantly inhibited with peak tumor concentration (12 µM) of CRT0066101 achieved within 2 h after oral administration. CRT0066101 given orally (80 mg/kg/day) for 21 days in Panc-1 orthotopic model potently blocks tumor growth in vivo. CRT0066101 significantly reduces Ki-67+ proliferation index (p< 0.01), increases TUNEL+ apoptotic cells (p<0.05), and abrogates expression of NF-κB-dependent proteins including cyclin D1, survivin, and cIAP-1. CRT0066101 blocks Panc-1 cell proliferation and growth in multiple xenograft models^[1]

プロトコル(参考用のみ)

細胞アッセイ	細胞株	Panc-1 cells
	濃度	5 μM
	反応時間	1 h
	実験の流れ	Panc-1 cells are either transfected with control (Panc-1) or PKD1 over-expressing (Panc-1-PKD1) vectors and 23 h post-transfection are treated with DMSO (−) or 5 µM CRT0066101 (+) for 1 h prior to preparation of nuclear extracts (NE) for measuring NF-κB activation by EMSA
動物実験	動物モデル	CR-UK nu/nu mice
	投薬量	80 mg/kg
	投与方法	by oral gavage

参考

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：

Golgi retention and oncogenic KIT signaling via PLCγ2-PKD2-PI4KIIIβ activation in gastrointestinal stromal tumor cells [ Cell Rep, 2023, 42(9):113035]	PubMed: 37616163
Protein Kinase D3 (PKD3) Requires Hsp90 for Stability and Promotion of Prostate Cancer Cell Migration [ Cells, 2023, 12(2)212]	PubMed: 36672148
Estrogen receptor alpha mutations regulate gene expression and cell growth in breast cancer through microRNAs [ NAR Cancer, 2023, 5(2):zcad027]	PubMed: 37275275
Estrogen receptor alpha mutations regulate gene expression and cell growth in breast cancer through microRNAs [ NAR Cancer, 2023, 5(2):zcad027]	PubMed: 37275275
Novel Treatments of Uveal Melanoma Identified with a Synthetic Lethal CRISPR/Cas9 Screen [ Cancers (Basel), 2022, 14(13)3186]	PubMed: 35804957
Protein Kinase D-Dependent Downregulation Of Immediate Early Genes Through Class IIa Histone Deacetylases In Acute Lymphoblastic Leukemia [ Mol Cancer Res, 2021, molcanres.0808.2020]	PubMed: 33980612
Functions of protein kinase D in β-cell regulation and breast cancer stem cell maintenance [ University of Stuttgart, 2020, N/A]	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。