RMC-4550

製品コードS8718 バッチS871803

印刷

化学情報

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

DMSO

87 mg/mL (198.92 mM)

Ethanol

30 mg/mL (68.59 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.

* <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 は、IC50 が 1.55 nM の強力な SHP-2 阻害剤であり、468 種類のキナーゼ、15 種類のホスファターゼの触媒ドメイン、および GPCR、トランスポーター、イオンチャネルを含むその他の細胞ターゲットに対して有意な活性を示しません。
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。

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。