受注:045-509-1970 |
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder | |
化学式 | C21H26Cl2N4O2 |
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分子量 | 437.36 | CAS No. | 2172651-73-7 | |
Solubility (25°C)* | 体外 | DMSO | 100 mg/mL (228.64 mM) | |
* <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. |
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. |
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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]. |
細胞アッセイ | 細胞株 | HEK-293 cells |
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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% /. Expression of SOS1 constructs is induced by the addition 0.1 μg/mL 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% / (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. |
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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 |
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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。
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。