Rociletinib

Summary

Rociletinib (CHEMBL3545308) is a phase-3 clinical-stage small molecule (ATC L01EB05) targeting EGFR; indicated across 2 conditions including non-small cell lung carcinoma and neoplasm; with CIViC clinical evidence for 3 variant-indication associations (e.g. EGFR T790M in lung non-small cell carcinoma).

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• ATC class: L01EB05
• Targets: 1 (EGFR)
• Indications: 2 conditions
• Clinical trials: 8
• Precision-oncology evidence (CIViC): 3 variant–indication associations
• Chemistry: 555.6 Da · C27H28F3N7O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3545308
Name	Rociletinib
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	57335384
ATC	L01EB05
Molecular formula	C27H28F3N7O3
Molecular weight	555.6
InChIKey	HUFOZJXAKZVRNJ-UHFFFAOYSA-N

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

IUPAC name: N-[3-[[2-[4-(4-acetylpiperazin-1-yl)-2-methoxyanilino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]phenyl]prop-2-enamide

Also known as: AVL-301, CNX-419, CO-1686, CS-1631, Rociletinib, ROCILETINIB, 8JC, ROCILETINIB HYDROBROMIDE, CO 1686, ROCILETINIB (CO-1686), US8975249, I-4

Patent coverage: 729 distinct patent families (1,729 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 1,608 (93%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
EGFR	epidermal growth factor receptor	Inhibition	6.52	17.5%	P00533

Broader ChEMBL bioactivity targets: 12 (assay-derived). Sample: Epidermal growth factor receptor, Tyrosine-protein kinase JAK3, Focal adhesion kinase 1, Tyrosine-protein kinase Fer, Dual specificity protein kinase CLK1, Tyrosine-protein kinase Tec, ALK tyrosine kinase receptor, Cyclin-G-associated kinase, Tyrosine-protein kinase BTK, Non-receptor tyrosine-protein kinase TNK1.

Bioactivity

ChEMBL activities: 88 potent at pChembl ≥ 5 of 88 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
EGFR	8.89	IC50	1.3	nM	CHEMBL_ACT_27619442
EGFR	8.89	IC50	1.3	nM	CHEMBL_ACT_27619454
EGFR	8.85	Kd	1.4	nM	CHEMBL_ACT_27102788
EGFR	8.78	Ki	1.65	nM	CHEMBL_ACT_15685234
EGFR	8.77	IC50	1.7	nM	CHEMBL_ACT_18039996
EGFR	8.77	Ki	1.7	nM	CHEMBL_ACT_18040100
EGFR	8.76	Ki	1.75	nM	CHEMBL_ACT_15685230
EGFR	8.74	Ki	1.8	nM	CHEMBL_ACT_18040093
EGFR	8.74	IC50	1.8	nM	CHEMBL_ACT_22894036
EGFR	8.7	IC50	2	nM	CHEMBL_ACT_15685113
EGFR	8.7	IC50	2	nM	CHEMBL_ACT_15685168
EGFR	8.7	IC50	2	nM	CHEMBL_ACT_18189803
EGFR	8.7	IC50	2	nM	CHEMBL_ACT_18189840
EGFR	8.68	IC50	2.1	nM	CHEMBL_ACT_27619418
EGFR	8.59	IC50	2.6	nM	CHEMBL_ACT_18039952
EGFR	8.52	IC50	3	nM	CHEMBL_ACT_15685206
EGFR	8.52	IC50	3	nM	CHEMBL_ACT_18189871
EGFR	8.39	IC50	4.1	nM	CHEMBL_ACT_16752452
EGFR	8.38	IC50	4.19	nM	CHEMBL_ACT_24731169
EGFR	8.37	IC50	4.3	nM	CHEMBL_ACT_17998426
JAK3	8.37	IC50	4.3	nM	CHEMBL_ACT_29122990
EGFR	8.26	IC50	5.5	nM	CHEMBL_ACT_16335936
EGFR	8.26	IC50	5.5	nM	CHEMBL_ACT_27749102
EGFR	8.26	IC50	5.5	nM	CHEMBL_ACT_28460930
EGFR	8.15	Kd	7	nM	CHEMBL_ACT_16444133
EGFR	8.05	IC50	9	nM	CHEMBL_ACT_16540166
EGFR	8.05	IC50	9	nM	CHEMBL_ACT_18450678
EGFR	7.86	IC50	13.8	nM	CHEMBL_ACT_16752453
EGFR	7.86	IC50	13.7	nM	CHEMBL_ACT_27322283
EGFR	7.84	IC50	14.3	nM	CHEMBL_ACT_16444025

Target pathways

Aggregated over 1 target gene(s): EGFR.

Top Reactome pathways

37 total, by targets touching each:

Pathway	Targets	Genes
Signaling by ERBB2	1	EGFR
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	1	EGFR
Signaling by ERBB4	1	EGFR
SHC1 events in ERBB2 signaling	1	EGFR
PLCG1 events in ERBB2 signaling	1	EGFR
PIP3 activates AKT signaling	1	EGFR
Signaling by EGFR	1	EGFR
GRB2 events in EGFR signaling	1	EGFR
GAB1 signalosome	1	EGFR
SHC1 events in EGFR signaling	1	EGFR
EGFR downregulation	1	EGFR
GRB2 events in ERBB2 signaling	1	EGFR
PI3K events in ERBB2 signaling	1	EGFR
EGFR interacts with phospholipase C-gamma	1	EGFR
EGFR Transactivation by Gastrin	1	EGFR
Constitutive Signaling by Aberrant PI3K in Cancer	1	EGFR
Signal transduction by L1	1	EGFR
Constitutive Signaling by EGFRvIII	1	EGFR
Inhibition of Signaling by Overexpressed EGFR	1	EGFR
RAF/MAP kinase cascade	1	EGFR
ERBB2 Regulates Cell Motility	1	EGFR
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	EGFR
ERBB2 Activates PTK6 Signaling	1	EGFR
Cargo recognition for clathrin-mediated endocytosis	1	EGFR
Clathrin-mediated endocytosis	1	EGFR
PTK6 promotes HIF1A stabilization	1	EGFR
Downregulation of ERBB2 signaling	1	EGFR
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	1	EGFR
Extra-nuclear estrogen signaling	1	EGFR
NOTCH3 Activation and Transmission of Signal to the Nucleus	1	EGFR

Dominant GO biological processes

GO term	Targets
cell morphogenesis	1
ossification	1
embryonic placenta development	1
positive regulation of protein phosphorylation	1
hair follicle development	1
ubiquitin-dependent protein catabolic process	1
signal transduction	1
cell surface receptor signaling pathway	1
epidermal growth factor receptor signaling pathway	1
salivary gland morphogenesis	1
learning or memory	1
positive regulation of cell population proliferation	1
gene expression	1
protein ubiquitination	1
cerebral cortex cell migration	1

Indications & clinical

Indications

2 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
non-small cell lung carcinoma	3	MONDO:0005233	EFO:0003060
neoplasm	3	MONDO:0005070	EFO:0000616

Clinical trials

Total trials: 8.

Phase distribution

Phase	Trials
PHASE1/PHASE2	3
PHASE2	2
PHASE2/PHASE3	1
PHASE3	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02186301	PHASE2/PHASE3	TERMINATED	TIGER-1: Safety and Efficacy Study of Rociletinib (CO-1686) or Erlotinib in Patients With EGFR-mutant/Metastatic NSCLC Who Have Not Had Any Previous EGFR Directed Therapy
NCT02322281	PHASE3	TERMINATED	TIGER-3: Open Label, Multicenter Study of Rociletinib (CO-1686) Mono Therapy Versus Single-agent Cytotoxic Chemotherapy in Patients With Mutant EGFR NSCLC Who Have Failed at Least One Previous EGFR-Directed TKI and Platinum-doublet Chemotherapy
NCT01526928	PHASE1/PHASE2	TERMINATED	Study to Evaluate Safety, Pharmacokinetics, and Efficacy of Rociletinib (CO-1686) in Previously Treated Mutant Epidermal Growth Factor Receptor (EGFR) in Non-Small Cell Lung Cancer (NSCLC) Patients
NCT02147990	PHASE2	TERMINATED	Multicenter Study of Rociletinib Administered to Patients With Previously Treated Mutant EGFR Non-small Cell Lung Cancer
NCT02580708	PHASE1/PHASE2	TERMINATED	Phase 1/2 Study of the Safety and Efficacy of Rociletinib in Combination With Trametinib in Patients With mEGFR-positive Advanced or Metastatic Non-small Cell Lung Cancer
NCT02630186	PHASE1/PHASE2	TERMINATED	A Phase 1b/2 Study of Safety and Efficacy of Rociletinib in Combination With MPDL3280A in Patients With Advanced or Metastatic EGFR-mutant NSCLC
NCT02705339	PHASE2	WITHDRAWN	Rociletinib Genomic Landscape in Non-small Cell Lung Cancer (NSCLC)
NCT02547675	Not specified	NO_LONGER_AVAILABLE	Rociletinib (CO-1686) USA Expanded Access Program

Clinical evidence (CIViC)

Variant × indication × effect (3 predictive associations from 4 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
EGFR T790M	Lung Non-small Cell Carcinoma	Sensitivity/Response	Rociletinib	CIViC B	EID646 +1
EGFR T790M	Lung Non-small Cell Carcinoma	Sensitivity/Response	Rociletinib + Osimertinib	CIViC D	EID967
EGFR Amplification	Lung Non-small Cell Carcinoma	Resistance	Osimertinib + Rociletinib	CIViC D	EID3015

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

157 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
AFATINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR
SELUMETINIB	ChEMBL + PubChem	Phase 4 (approved)	EGFR
ABEMACICLIB	ChEMBL	Phase 4 (approved)	EGFR
ACALABRUTINIB	ChEMBL	Phase 4 (approved)	EGFR
AFATINIB DIMALEATE	ChEMBL	Phase 4 (approved)	EGFR
ALECTINIB	ChEMBL	Phase 4 (approved)	EGFR
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	EGFR
AXITINIB	ChEMBL	Phase 4 (approved)	EGFR
BACITRACIN	ChEMBL	Phase 4 (approved)	EGFR
BITHIONOL	ChEMBL	Phase 4 (approved)	EGFR
BOSUTINIB	ChEMBL	Phase 4 (approved)	EGFR
BRIGATINIB	ChEMBL	Phase 4 (approved)	EGFR
CABOZANTINIB	ChEMBL	Phase 4 (approved)	EGFR
CERITINIB	ChEMBL	Phase 4 (approved)	EGFR
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	EGFR
CHROMIC CHLORIDE	ChEMBL	Phase 4 (approved)	EGFR
CISPLATIN	ChEMBL	Phase 4 (approved)	EGFR
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	EGFR
COLISTIN	ChEMBL	Phase 4 (approved)	EGFR
CRIZOTINIB	ChEMBL	Phase 4 (approved)	EGFR
DACOMITINIB	ChEMBL	Phase 4 (approved)	EGFR
DASATINIB	ChEMBL	Phase 4 (approved)	EGFR
DOBUTAMINE	ChEMBL	Phase 4 (approved)	EGFR
DOCETAXEL	ChEMBL	Phase 4 (approved)	EGFR
EBASTINE	ChEMBL	Phase 4 (approved)	EGFR
ECONAZOLE	ChEMBL	Phase 4 (approved)	EGFR
ERLOTINIB	ChEMBL	Phase 4 (approved)	EGFR
FEDRATINIB	ChEMBL	Phase 4 (approved)	EGFR
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	EGFR
GEFITINIB	ChEMBL	Phase 4 (approved)	EGFR
GENTIAN VIOLET	ChEMBL	Phase 4 (approved)	EGFR
GILTERITINIB	ChEMBL	Phase 4 (approved)	EGFR
HEXACHLOROPHENE	ChEMBL	Phase 4 (approved)	EGFR
IBRUTINIB	ChEMBL	Phase 4 (approved)	EGFR
IMATINIB	ChEMBL	Phase 4 (approved)	EGFR
LAPATINIB	ChEMBL	Phase 4 (approved)	EGFR
LAPATINIB DITOSYLATE	ChEMBL	Phase 4 (approved)	EGFR
LAZERTINIB	ChEMBL	Phase 4 (approved)	EGFR
LEVODOPA	ChEMBL	Phase 4 (approved)	EGFR
LORLATINIB	ChEMBL	Phase 4 (approved)	EGFR
METHYLDOPA	ChEMBL	Phase 4 (approved)	EGFR
MICONAZOLE	ChEMBL	Phase 4 (approved)	EGFR
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	EGFR
MITOXANTRONE	ChEMBL	Phase 4 (approved)	EGFR
MOBOCERTINIB	ChEMBL	Phase 4 (approved)	EGFR
MONTELUKAST	ChEMBL	Phase 4 (approved)	EGFR
NELFINAVIR	ChEMBL	Phase 4 (approved)	EGFR
NERATINIB	ChEMBL	Phase 4 (approved)	EGFR
NICLOSAMIDE	ChEMBL	Phase 4 (approved)	EGFR
OLMUTINIB	ChEMBL	Phase 4 (approved)	EGFR
OSIMERTINIB	ChEMBL	Phase 4 (approved)	EGFR
PERHEXILINE	ChEMBL	Phase 4 (approved)	EGFR
PONATINIB	ChEMBL	Phase 4 (approved)	EGFR
SORAFENIB	ChEMBL	Phase 4 (approved)	EGFR
SULOCTIDIL	ChEMBL	Phase 4 (approved)	EGFR
SUNITINIB	ChEMBL	Phase 4 (approved)	EGFR
TAMOXIFEN	ChEMBL	Phase 4 (approved)	EGFR
TERFENADINE	ChEMBL	Phase 4 (approved)	EGFR
THIORIDAZINE	ChEMBL	Phase 4 (approved)	EGFR
TRIBROMSALAN	ChEMBL	Phase 4 (approved)	EGFR