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| Targets |
Rociletinib targets mutant forms of the epidermal growth factor receptor (EGFR), specifically the T790M mutation that confers resistance to first-generation EGFR inhibitors. The compound is an irreversible/covalent inhibitor that selectively targets mutant EGFR over wild-type EGFR. Ki values are 21.5 nM for EGFR L858R/T790M and 303.3 nM for EGFR WT.
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| ln Vitro |
Rociletinib (0.1 μM) potently and irreversibly inhibits EGFR and inhibits more than 50% of 23 targets. Rociletinib potently and specifically inhibits the proliferation and promotes death of NSCLC cells expressing mutant EGFR. Rociletinib-resistant NSCLC cell lines are responsive to AKT inhibition [1].
In vitro, Rociletinib inhibits mutant EGFR with Ki values of 21.5 nM for EGFR L858R/T790M and 303.3 nM for EGFR WT, demonstrating selectivity for the mutant form. The compound is an irreversible and mutant-selective EGFR kinase inhibitor. Detailed IC₅0 values against specific mutant EGFR isoforms are not extensively documented. |
| ln Vivo |
An NSCLC xenograft model with an EGFR mutation shows antitumor efficacy when treated with rociletinib (100 mg/kg/day, orally). The anticancer efficacy of rociletinib (50 mg/kg bid, po) has been shown in transgenic mice that express human EGFR-L858R and EGFR-L858R-T790M [1].
In vivo activity data for Rociletinib are available from clinical studies. As an orally delivered EGFR mutant-selective inhibitor, the compound has shown efficacy in patients with EGFR-mutant non-small cell lung cancer (NSCLC) harboring the T790M resistance mutation. Further clinical data are available in the published literature. |
| Enzyme Assay |
The in vitro kinase inhibition assay for EGFR uses recombinant EGFR wild-type and mutant (L858R/T790M) kinases. Kinase activity is measured by incubating the enzyme with a peptide substrate and ATP in the presence of varying concentrations of Rociletinib. Phosphorylated substrate is quantified using radioactive ATP incorporation, fluorescence polarization, or luminescence-based methods. Ki values are calculated from dose-response curves.
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| Cell Assay |
For in vitro cell-based assays, NSCLC cell lines with EGFR mutations (such as H1975 cells with L858R/T790M) are cultured and treated with Rociletinib at various concentrations. Cell viability is measured using MTT, CellTiter-Glo, or other proliferation assays. EGFR phosphorylation is assessed by Western blot to confirm target inhibition. Selectivity for mutant over wild-type EGFR is confirmed using cells expressing wild-type EGFR. Experiments are typically performed in triplicate.
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| Animal Protocol |
In vivo animal studies for Rociletinib typically involve xenograft mouse models using EGFR-mutant NSCLC cell lines. Tumor-bearing mice are administered Rociletinib orally at various doses. Tumor volume is measured periodically using calipers, and tumor growth inhibition is assessed relative to vehicle-treated controls. At study termination, tumors are harvested for analysis of EGFR phosphorylation and downstream signaling. Pharmacokinetic studies may also be performed.
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| ADME/Pharmacokinetics |
Rociletinib is orally bioavailable with good systemic exposure. The compound has molecular formula C2₇H2₉BrF3N₇O3 and molecular weight 636.46. It is soluble in DMSO and typically formulated for oral administration. Further detailed PK parameters (half-life, Cmax, AUC) are available in the clinical literature.
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| Toxicity/Toxicokinetics |
Toxicological data for Rociletinib are available from clinical studies. As an EGFR inhibitor, potential side effects include rash, diarrhea, and hyperglycemia. The compound was investigated in clinical trials for NSCLC. Comprehensive safety data are available in the published clinical literature.
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| References | |
| Additional Infomation |
Rociletinib hydrobromide (CAS# 1446700-26-0) is an orally delivered, irreversible EGFR inhibitor that targets mutant forms including T790M. Ki values are 21.5 nM for EGFR L858R/T790M and 303.3 nM for EGFR WT. It is also known as CO-1686, AVL-301, and CNX-419. The compound was investigated clinically for NSCLC.
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| Molecular Formula |
C₂₇H₂₉BRF₃N₇O₃
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| Molecular Weight |
636.46
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| Exact Mass |
635.146
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| CAS # |
1446700-26-0
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| Related CAS # |
Rociletinib;1374640-70-6
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| PubChem CID |
71725151
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
41
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| Complexity |
871
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
IPKRDUJIGYXXNT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H28F3N7O3.BrH/c1-4-24(39)32-18-6-5-7-19(14-18)33-25-21(27(28,29)30)16-31-26(35-25)34-22-9-8-20(15-23(22)40-3)37-12-10-36(11-13-37)17(2)38;/h4-9,14-16H,1,10-13H2,2-3H3,(H,32,39)(H2,31,33,34,35);1H
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| Chemical Name |
N-[3-[[2-[4-(4-acetylpiperazin-1-yl)-2-methoxyanilino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]phenyl]prop-2-enamide;hydrobromide
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| Synonyms |
CO-1686 hydrobromide AVL-301 hydrobromide CNX-419 hydrobromideCO1686AVL-301 CNX419CO-1686 AVL 301 CNX 419CO 1686 AVL301 CNX-419.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 59 mg/mL (~92.70 mM)
H2O : < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.93 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (3.93 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5712 mL | 7.8560 mL | 15.7119 mL | |
| 5 mM | 0.3142 mL | 1.5712 mL | 3.1424 mL | |
| 10 mM | 0.1571 mL | 0.7856 mL | 1.5712 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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