RMC-4550

製品コードS8718 バッチS871804

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
化学式

C21H26Cl2N4O2
分子量 437.36 CAS No. 2172651-73-7
Solubility (25°C)* 体外 Ethanol 22 mg/mL (50.3 mM)
DMSO 11 mg/mL (25.15 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 40%PEG300 5%Tween80 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。

 4.350mg/ml (9.95mM) Taking the 1 mL working solution as an example, add 50 μL 87 mg/ml clarified DMSO stock solution to 400 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL 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 RMC-4550 is a potent SHP-2inhibitor with an IC50 of 1.55 nM and it has no significant activity vs. 468 kinases, the catalytic domain of 15 phosphatases and other cellular targets including GPCRs, transporters and ion channels.
in vitro

RMC-4550 inhibits purified, activated full length human SHP2 with an IC50 of 1.55 nM, and has cellular IC50 of 39 nM in PC9 cells with a pERK readout. This compound has no detectable inhibitory activity up to 10 µM against the catalytic domain of SHP2, a panel of 14 additional protein phosphatases, and a panel of 468 protein kinases. It exhibits low to moderate cross species in vitro intrinsic clearance (3.6-24 µL/min/million cells) in hepatocytes, a high passive permeability (458 nm/s) and efflux ratio of 1.
in vivo

RMC-4550 has moderate to high bioavailability and has a half-life amenable for once daily oral administration. In the EGFR-driven KYSE-520 human esophageal cancer xenograft model, this compound has a dose dependent efficacy consistent with target modulation, assessed by phospho-ERK inhibition in tumors. It is well tolerated at doses that achieved maximal and sustained efficacy in this model.

プロトコル(参考用のみ)

細胞アッセイ 細胞株 HEK-293 cells
濃度 --
反応時間 1 h
実験の流れ

30,000 HEK-293 cells per well are plated in 96-well plates in Biotin-free RPMI supplemented with 0.1% fetal bovine serum, 0.02% bovine serum albumin. Cells are treated with serial 3-fold dilutions of RMC-4550 diluted in biotin-free media supplemented with 0.02% bovine serum albumin (final DMSO concentration equivalent to 0.1%) for one hour. For the final 5 minutes of drug treatment, cells are stimulated with 50 ng/mL EGF, lysed and subjected to ERK1/2 phosphorylation analysis.
動物実験 動物モデル Female (6-8 week old) athymic nude mice implanted with NCI-H358 (Balb/c strain background) or MIA PaCa-2 (NCR nude strain background) tumor cells subcutaneously in the flank
投薬量 3-60 mg/kg
投与方法 PO

参考

  • http://cancerres.aacrjournals.org/content/78/13_Supplement/4878#
  • https://www.biorxiv.org/content/early/2017/09/14/188730

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：

Whole-exome tumor-agnostic ctDNA analysis enhances minimal residual disease detection and reveals relapse mechanisms in localized colon cancer [ Nat Cancer, 2025, 10.1038/s43018-025-00960-z] PubMed: 40301653
RIT1 Drives Oncogenic Transformation and is an Actionable Target in Lung Adenocarcinoma [ Cancer Res, 2025, 10.1158/0008-5472.CAN-24-3819] PubMed: 40644578
Single-molecule imaging quantifies oncogenic KRAS dynamics for enhanced accuracy of therapeutic efficacy assessment [ iScience, 2025, 28(9):113374] PubMed: 40949096
A Hotspot Phosphorylation Site on SHP2 Drives Oncoprotein Activation and Drug Resistance [ Res Sq, 2025, rs.3.rs-7032881] PubMed: 40799749
A Hotspot Phosphorylation Site on SHP2 Drives Oncoprotein Activation and Drug Resistance [ bioRxiv, 2025, 2025.06.11.659120] PubMed: 40667115
Targeted therapies prime oncogene-driven lung cancers for macrophage-mediated destruction [ J Clin Invest, 2024, 134(9)e169315] PubMed: 38483480
Preclinical translational platform of neuroinflammatory disease biology relevant to neurodegenerative disease [ J Neuroinflammation, 2024, 21(1):37] PubMed: 38297405
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
Kinetics of RTK activation determine ERK reactivation and resistance to dual BRAF/MEK inhibition in melanoma [ Cell Rep, 2023, 42(6):112570] PubMed: 37252843
Feedback activation of EGFR/wild-type RAS signaling axis limits KRASG12D inhibitor efficacy in KRASG12D-mutated colorectal cancer [ Oncogene, 2023, 42(20):1620-1633] PubMed: 37020035

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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