RKI-1447

製品コードS7195 バッチS719501

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

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

化学式

C₁₆H₁₄N₄O₂S

分子量

326.37

CAS No.

1342278-01-6

Solubility (25°C)*

体外

DMSO

65 mg/mL (199.16 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）

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.
Homogeneous suspension	15% Captisol 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。	10.000mg/ml (30.64mM)	Taking the 1 mL working solution as an example, take 10 mg of this product, add it to 1 ml of 15% Captisol clear solution, and mix evenly to form a uniform suspension. The mixed solution should be used immediately for optimal results.
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。	10.000mg/ml (30.64mM)	Taking the 1 mL working solution as an example, add 50 μL of 200 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。	0.250mg/ml (0.77mM)	Taking the 1 mL working solution as an example, add 50 μL of 5 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	RKI-1447 is a potent inhibitor of ROCK1 and ROCK2, with IC50 of 14.5 nM and 6.2 nM, respectively, has anti-invasive and antitumor activities.
in vitro	RKI-1447 is a cell-permeable pyridylthiazolyl-urea that acts as a potent, ATP site-targeting Rho Kinase inhibitor, displaying much reduced potency against PKA, PKN1/PRK1, p70S6K/RPS6kB1, AKT1, MRCKa/CDC42BPA (85.5%, 80.5%, 61.9%, 56.0%, and 50.4% inhibition, respectively, by 1 µM this compound) or 15 other kinases. Crystal structures of the this chemical/ROCK1 complex reveals that this inhibitor is a Type I kinase inhibitor that binds the ATP binding site through interactions with the hinge region and the DFG motif. It suppresses phosphorylation of the ROCK substrates MLC-2 and MYPT-1 in human cancer cells, but had no effect on the phosphorylation levels of the AKT, MEK, and S6 kinase at concentrations as high as 10 μM. This compound is also highly selective at inhibiting ROCK-mediated cytoskeleton re-organization (actin stress fiber formation) following LPA stimulation, but does not affect PAK-meditated lamellipodia and filopodia formation following PDGF and Bradykinin stimulation. It inhibits migration, invasion and anchorage-independent tumor growth of breast cancer cells. ^[1]
in vivo	RKI-1447 is highly effective at inhibiting the outgrowth of mammary tumors in a transgenic mouse model. Tumors from mice treated with this compound increases in size with an average percent change in tumor volume of only 8.8%. Thus, it inhibited mammary tumor growth by 87%, and on average the mammary tumors from Compared with those tumors from mice treated with the vehicle control, this chemical treated mice are 7.7-fold smaller. This compound treatments does not result in mouse weight loss. ^[1]

プロトコル(参考用のみ)

キナーゼアッセイ	Z-Lyte FRET kinase assay
キナーゼアッセイ	Kinase inhibition is measured using the Invitrogen Z-Lyte® FRET kinase assay with Ser/Thr 13 peptide substrate based on the myosin light chain sequence KKRPQRRYSNVF. This compound is tested on three separate days with 8 point dilutions performed in duplicate to determine average IC50 values. The assay conditions are optimized to 15 μL of kinase reaction volume with 5 ng of enzyme in 50 mM HEPES (pH 7.5), 10 mM MgCl₂, 1 mM EGTA, and 0.01% Brij-35. The reaction is incubated for 1 h at room temperature in the presence of 1.5 μM of peptide substrate with 12.5 μM of ATP (for ROCK1) or 2 μM of substrate with 50 μM of ATP (for ROCK2).
細胞アッセイ	細胞株	MDA-MB-231
	濃度	~600 μM
	反応時間	72 h
	実験の流れ	Cells are plated in a 96 well tissue culture plate (1200 cells per well) and incubated for 24 hours. After incubation the cells are treated with vehicle or increasing concentrations of RKI-1447 for 72 hours. After incubation, freshly prepared MTT (2mg/ml) is added to each well and incubated for 3 hours. After incubation the plates are read at 540 nm.
動物実験	動物モデル	MMTV/neu transgenic mice [FVB/N-Tg (MMTVneu) 202 Mul/J]
	投薬量	200 mpk/day
	投与方法	i.p.

参考

https://pubmed.ncbi.nlm.nih.gov/22846914/
https://pubmed.ncbi.nlm.nih.gov/23275831/

カスタマーフィードバック

: Data from [Data independently produced by , , Oncogene, 2016, 1-10.]

: Data from [Data independently produced by , , Neoplasia, 2018, 20(1):44-56]

: Data from [Data independently produced by , , Anticancer Res, 2017, 37(4):1805-1818]

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：

Therapeutic targeting of tumor spheroids in a 3D microphysiological renal cell carcinoma-on-a-chip system [ Neoplasia, 2023, 10.1016/j.neo.2023.100948]	PubMed: 37944353
Correlating Basal Gene Expression across Chemical Sensitivity Data to Screen for Novel Synergistic Interactors of HDAC Inhibitors in Pancreatic Carcinoma [ Pharmaceuticals (Basel), 2023, 16(2)294]	PubMed: 37259439
Establishment and characterization of immortalized sweat gland myoepithelial cells [ Sci Rep, 2022, 12(1):7]	PubMed: 34997030
İnsan kornea endotel hücreleri üzerine farklı RHO kinaz inhibitörlerinin etkinliğinin araştırılması [ GCRIS, 2022, ]	PubMed: none
Synapse-specific Lrp4 mRNA enrichment requires Lrp4/MuSK signaling, muscle activity and Wnt non-canonical pathway [ Cell Biosci, 2021, 11(1):105]	PubMed: 34090516
RKI-1447 suppresses colorectal carcinoma cell growth via disrupting cellular bioenergetics and mitochondrial dynamics. [ J Cell Physiol, 2020, 235(1):254-266]	PubMed: 31237697
A novel human colon signet-ring cell carcinoma organoid line: establishment, characterization and application [ Carcinogenesis, 2020, 41(7):993-1004]	PubMed: 31740922
[ Cell Rep, 2019, ]	PubMed: 31825822
FUS-CHOP Promotes Invasion in Myxoid Liposarcoma through a SRC/FAK/RHO/ROCK-Dependent Pathway [Tornin J Neoplasia, 2018, 20(1):44-56]	PubMed: 29190494
Prominent oncogenic roles of EVI1 in breast carcinoma [Wang H Cancer Res, 2017, 77(8):2148-2160]	PubMed: 28209621

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。