Home Protein Tyrosine Kinase EGFR inhibitor Rociletinib (CO-1686) For research use only.

Rociletinib (CO-1686)

Synonyms: AVL-301

Rociletinib (CO-1686, AVL-301) is an irreversible, mutant-selective EGFR inhibitor with Ki of 21.5 nM and 303.3 nM for EGFRL858R/T790M and EGFRWT in cell-free assays, respectively. Phase 2.

Rociletinib (CO-1686) Chemical Structure

Rociletinib (CO-1686) Chemical Structure

CAS No. 1374640-70-6

Purity & Quality Control

Rociletinib (CO-1686) Related Products

Signaling Pathway

EGFR Signaling Pathways

EGFR Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
NCI-H1975 Kinase assay ~5 μM DMSO inhibits pEGFR with IC50 of 62 nM 24065731
HCC827 Kinase assay ~5 μM DMSO inhibits pEGFR with IC50 of 187 nM 24065731
HCC827-EPR Kinase assay ~5 μM DMSO inhibits pEGFR with IC50 of 180 nM 24065731
PC9 Kinase assay ~5 μM DMSO inhibits pEGFR with IC50 of 211 nM 24065731
A431 Kinase assay ~5 μM DMSO inhibits pEGFR with IC50 of >4331 nM 24065731
NCI-H1299 Kinase assay ~5 μM DMSO inhibits pEGFR with IC50 of >2000 nM 24065731
NCI-H358 Kinase assay ~5 μM DMSO inhibits pEGFR with IC50 of >2000 nM 24065731
NCI-H1975 Growth inhibitory assay ~5 μM DMSO GI50=32 nM 24065731
HCC827 Growth inhibitory assay ~5 μM DMSO GI50=7 nM 24065731
HCC827-EPR Growth inhibitory assay ~5 μM DMSO GI50=20 nM 24065731
PC9 Growth inhibitory assay ~5 μM DMSO GI50=26 nM 24065731
A431 Growth inhibitory assay ~5 μM DMSO GI50=547 nM 24065731
NCI-H1299 Growth inhibitory assay ~5 μM DMSO GI50=4275 nM 24065731
NCI-H358 Growth inhibitory assay ~5 μM DMSO GI50=1806 nM 24065731
PC-9 (exon 19del) Growth inhibitory assay ~10 μM DMSO IC50=84 nM 26515464
H3255 (L858R) Growth inhibitory assay ~10 μM DMSO IC50=35 nM 26515464
PC-9ER (exon 19del+T790M) Growth inhibitory assay ~10 μM DMSO IC50=37 nM 26515464
H1975 (L858R+T790M) Growth inhibitory assay ~10 μM DMSO IC50=23 nM 26515464
BID007 (A763_Y764insFQEA) Growth inhibitory assay ~10 μM DMSO IC50=1278 nM 26515464
Ba/F3 (FQEA) Growth inhibitory assay ~10 μM DMSO IC50=673 nM 26515464
Ba/F3 (HH) Growth inhibitory assay ~10 μM DMSO IC50=1730 nM 26515464
Ba/F3 (ASV) Growth inhibitory assay ~10 μM DMSO IC50=5290 nM 26515464
Ba/F3 (FQEA) Growth inhibitory assay ~10 μM DMSO IC50=262 nM 26515464
Click to View More Cell Line Experimental Data

Biological Activity

Description Rociletinib (CO-1686, AVL-301) is an irreversible, mutant-selective EGFR inhibitor with Ki of 21.5 nM and 303.3 nM for EGFRL858R/T790M and EGFRWT in cell-free assays, respectively. Phase 2.
Targets
EGFR (L858R/T790M) [1]
(Cell-free assay)		 EGFR (wt) [1]
(Cell-free assay)
21.5 nM(Ki) 303.3 nM(Ki)
In vitro
In vitro CO-1686 inhibits p-EGFR with IC50 ranging from 62 to 187 nM in the mutant EGFR–expressing cells, while inhibits EGFR phosphorylation with IC50 of > 2,000 nM in the three WT EGFR–expressing cells. CO-1686 selectively inhibits growth of NSCLC cells expressing mutant EGFR with GI50 ranging from 7 to 32 nM, and induces apoptosis. CO-1686–resistant NSCLC cell lines exhibits signs of epithelial-mesenchymal transition and increased sensitivity to AKT inhibitors. [1]
Kinase Assay Inhibition Kinetics Studies
Recombinant human wild-type and T790M/L858R double mutant EGFR, both Nterminal GST-tagged, are used in the assay. The Omnia continuous read assay is performed as described by the vendor.
Cell Research Cell lines NSCLC cell lines expressing mutant EGFR (HCC827, PC9, HCC827-EPR, and NCI-H1975) and cell lines expressing WT EGFR (A431, NCI-H1299, and NCI-H358)
Concentrations ~10 μM
Incubation Time 72 hours
Method Cells are seeded at 3,000 cells per well in growth media supplemented with 5% FBS, 2 mmol/L, L-glutamine, and 1% penicillin–streptomycin, allowed to adhere overnight, and treated with a dilution series of test compounds for 72 hours. Cell viability is determined by CellTiter-Glo, and results are represented as background-subtracted relative light units normalized to a dimethyl sulfoxide (DMSO)–treated control. Growth inhibition (GI 50) values are determined by GraphPad Prism 5.04. MK-2206 and XL-880 compounds are obtained from Selleck Chemical. CI data are generated using CalcuSyn.
In Vivo
In vivo CO-1686 causes dose-dependent and significant tumor growth inhibition in all EGFR-mutant models as well as human EGFRL858R- and EGFRL858R/T790M-expressing transgenic mice. [1]
Animal Research Animal Models Human EGFRL858R- and EGFRL858R/T790M-expressing transgenic mice.
Dosages ~50 mg/kg
Administration Oral gavage
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02630186 Terminated
Non-small Cell Lung Cancer
Clovis Oncology Inc.|Genentech Inc.
 February 24 2016 Phase 1|Phase 2
NCT02580708 Terminated
Non-small Cell Lung Cancer
Clovis Oncology Inc.|Novartis Pharmaceuticals
 September 30 2015 Phase 1|Phase 2
NCT02147990 Terminated
Non-small Cell Lung Cancer
Clovis Oncology Inc.
 June 16 2014 Phase 2
NCT01526928 Terminated
Locally Advanced or Metastatic Non Small Cell Lung Cancer
Clovis Oncology Inc.
 March 27 2012 Phase 1|Phase 2

Chemical Information & Solubility

Molecular Weight 555.55 Formula

C27H28F3N7O3
CAS No. 1374640-70-6 SDF Download Rociletinib (CO-1686) SDF
Smiles CC(=O)N1CCN(CC1)C2=CC(=C(C=C2)NC3=NC=C(C(=N3)NC4=CC(=CC=C4)NC(=O)C=C)C(F)(F)F)OC
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (180.0 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


Molecular Weight Calculator

In vivo
Batch:

Add solvents to the product individually and in order.


In vivo Formulation Calculator

Preparing Stock Solutions

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.
Tags: buy Rociletinib (CO-1686) | Rociletinib (CO-1686) supplier | purchase Rociletinib (CO-1686) | Rociletinib (CO-1686) cost | Rociletinib (CO-1686) manufacturer | order Rociletinib (CO-1686) | Rociletinib (CO-1686) distributor