RMC-4550

製品コードS8718 バッチS871803

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 DMSO 87 mg/mL (198.92 mM)
Ethanol 30 mg/mL (68.59 mM)
Water Insoluble
* <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. RMC-4550 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. RMC-4550 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[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, RMC-4550 has a dose dependent efficacy consistent with target modulation, assessed by phospho-ERK inhibition in tumors. RMC-4550 is well tolerated at doses that achieved maximal and sustained efficacy in this model[1].

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 and 1% penicillin/streptomycin. Expression of SOS1 constructs is induced by the addition 0.1 μg/mL doxycycline for 24 hours. Cells are treated with serial 3-fold dilutions of RMC-4550 diluted in biotin-free media supplemented with 0.02% bovine serum albumin and 1% penicillin/streptomycin (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

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：

Preclinical translational platform of neuroinflammatory disease biology relevant to neurodegenerative disease [ J Neuroinflammation, 2024, 21(1):37] PubMed: 38297405
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
Feedback activation of EGFR/wild-type RAS signaling axis limits KRASG12D inhibitor efficacy in KRASG12D-mutated colorectal cancer [ Oncogene, 2023, 10.1038/s41388-023-02676-9 10.3322/caac.21660 10.1001/jama.2021.6021 10.1038/nrdp.2015.65 10.1038/s41575-019-0189-8 10.1038/nature11252 10.1038/s41392] PubMed: 37020035
SHP2 inhibitors maintain TGFβ signalling through SMURF2 inhibition [ NPJ Precis Oncol, 2023, 7(1):136] PubMed: 38102334
Rational combination of SHP2 and mTOR inhibition for the treatment of hepatocellular carcinoma [ Mol Oncol, 2023, none] PubMed: 36650715
SHP2 participates in decidualization by activating ERK to maintain normal nuclear localization of progesterone receptor [ Reproduction, 2023, 166(1):37-53] PubMed: 37184079
RAS-dependent RAF-MAPK hyperactivation by pathogenic RIT1 is a therapeutic target in Noonan syndrome-associated cardiac hypertrophy [ Sci Adv, 2023, 9(28):eadf4766] PubMed: 37450595
RAS-dependent RAF-MAPK hyperactivation by pathogenic RIT1 is a therapeutic target in Noonan syndrome-associated cardiac hypertrophy [ Sci Adv, 2023, 9(28):eadf4766] PubMed: 37450595
Targeted therapies prime oncogene-driven lung cancers for macrophage-mediated destruction [ bioRxiv, 2023, 2023.03.03.531059] PubMed: 36945559

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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