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Compound Detail

CHEMBL3545308

ROCILETINIB
🧪 Phase III
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🧪 Phase III
C=CC(=O)Nc1cccc(Nc2nc(Nc3ccc(N4CCN(C(C)=O)CC4)cc3OC)ncc2C(F)(F)F)c1

Basic Information

ChEMBL ID CHEMBL3545308
Name ROCILETINIB
Phase Phase III
Structure Type MOL
InChI Key HUFOZJXAKZVRNJ-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

AVL-301 CNX-419 CO-1686 CS-1631 Rociletinib
21
Targets
127
Activities
4
Assay Types
4
PK Parameters
20
Publications
5
Known Names
2
Indications
1
Mechanisms

Molecular Properties

555.6
MW (Da)
4.78
ALogP
8
HBA
3
HBD
111.7
PSA (Ų)
0.34
QED
1
Ro5 Violations
8
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Achiral
USAN Stem -tinib
USAN Year 2014

Extended Properties

Molecular Formula C27H28F3N7O3
MW 555.56
Aromatic Rings 3
Heavy Atoms 40
NP-Likeness -1.48

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Epidermal growth factor receptor erbB1 inhibitor INHIBITOR Epidermal growth factor receptor

Indications

Carcinoma, Non-Small-Cell Lung Neoplasms

ATC Classification

L01EB05
rociletinib
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 101 meas. best 8.89
Kd 13 meas. best 8.85
Ki 7 meas. best 8.78
EC50 6 meas. best 7.35

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Epidermal growth factor receptor
CHEMBL203
IC50 8.89 7.498 1.3 59
Epidermal growth factor receptor
CHEMBL203
Kd 8.85 7.5125 1.4 4
Epidermal growth factor receptor
CHEMBL203
Ki 8.78 8.0543 1.6 7
HEK293
CHEMBL614818
IC50 8.14 8.03 7.2 2
Unchecked
CHEMBL612545
IC50 8.05 6.9657 9.0 7
NCI-H1975
CHEMBL614348
IC50 7.64 6.9938 23.0 8
HCC827
CHEMBL4296422
IC50 7.51 7.51 31.0 3
Epidermal growth factor receptor
CHEMBL203
EC50 7.35 6.6867 45.0 3
HCC827
CHEMBL4296422
EC50 7.35 7.35 45.0 1
Receptor tyrosine-protein kinase erbB-3
CHEMBL5838
IC50 7.34 7.34 46.0 1
PC-9
CHEMBL614102
IC50 7.08 6.825 84.0 2
NCI-H1975
CHEMBL614348
EC50 7.0 7.0 100.0 1
NON-PROTEIN TARGET
CHEMBL3879801
IC50 6.86 5.98 137.0 3
ALK tyrosine kinase receptor
CHEMBL4247
IC50 6.84 6.84 145.0 1
Non-receptor tyrosine-protein kinase TNK1
CHEMBL5334
Kd 6.54 6.54 289.0 1
Tyrosine-protein kinase Tec
CHEMBL4246
Kd 6.54 6.54 288.0 1
Focal adhesion kinase 1
CHEMBL2695
Kd 6.36 6.36 433.0 1
Cyclin-G-associated kinase
CHEMBL4355
Kd 6.35 6.35 450.0 1
Tyrosine-protein kinase BTK
CHEMBL5251
Kd 6.26 6.26 547.0 1
A-431
CHEMBL614069
IC50 6.19 5.7683 641.0 6
Dual specificity protein kinase CLK1
CHEMBL4224
Kd 6.19 6.19 651.0 1
Tyrosine-protein kinase Fer
CHEMBL3982
Kd 5.96 5.96 1110.0 1
Tyrosine-protein kinase Fes/Fps
CHEMBL5455
Kd 5.92 5.92 1194.0 1
A-431
CHEMBL614069
EC50 5.78 5.78 1660.0 1
A549
CHEMBL392
IC50 5.49 5.3225 3240.0 4
COS-7
CHEMBL614564
IC50 5.13 5.13 7390.0 1
SW-620
CHEMBL612262
IC50 4.98 4.98 10500.0 1
Unchecked
CHEMBL612545
Kd 4.87 4.87 13533.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 81.0 mL.min-1.g-1 Mus musculus
CL 5.1 mL.min-1.g-1 Homo sapiens
F 65.0 % Mus musculus
Fu 0.01 - Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Epidermal growth factor receptor IC50 = 1.3 nM 8.89 Assay on In Vitro Enzyme-Inhibiting Activity: Test compounds: a part of compound... -
Epidermal growth factor receptor IC50 = 1.3 nM 8.89 Assay on In Vitro Enzyme-Inhibiting Activity: Test compounds: a part of compound... -
Epidermal growth factor receptor Kd = 1.4 nM 8.85 EGFR in vitro assay: Kinase-tagged T7 phage strains were prepared in an E. coli ... -
Epidermal growth factor receptor Ki = 1.65 nM 8.78 Inhibition of EGFR L858R/T790M mutant (unknown origin) expressed in Sf9 cells by... 26275028
Epidermal growth factor receptor Ki = 1.7 nM 8.77 Reversible inhibition of human N-terminal GST-tagged EGFR L858R/T790M double mut... 28225269
Epidermal growth factor receptor IC50 = 1.7 nM 8.77 Inhibition of wild-type human N-terminal GST-tagged EGFR cytoplasmic domain (669... 28225269
Epidermal growth factor receptor Ki = 1.75 nM 8.76 Inhibition of EGFR L858R mutant (unknown origin) expressed in Sf9 cells by enzym... 26275028
Epidermal growth factor receptor Ki = 1.8 nM 8.74 Reversible inhibition of human N-terminal GST-tagged EGFR L858R mutant cytoplasm... 28225269
Epidermal growth factor receptor IC50 = 1.8 nM 8.74 Inhibition of recombinant human EGFR T790M/L858R mutant expressed in baculovirus... 32912431
Epidermal growth factor receptor IC50 = 2.0 nM 8.7 Inhibition of wild type EGFR (unknown origin) expressed in Sf9 cells pre-incubat... 26275028
Epidermal growth factor receptor IC50 = 2.0 nM 8.7 Inhibition of EGFR L858R mutant (unknown origin) expressed in Sf9 cells pre-incu... 26275028
Epidermal growth factor receptor IC50 = 2.0 nM 8.7 Inhibition of wild type N-terminal GST-fused human EGFR cytoplasmic domain expre... 28853575
Epidermal growth factor receptor IC50 = 2.0 nM 8.7 Inhibition of human recombinant GST-tagged EGFR L858R mutant expressed in baculo... 28853575
Epidermal growth factor receptor IC50 = 2.1 nM 8.68 Assay on In Vitro Enzyme-Inhibiting Activity: Test compounds: a part of compound... -
Epidermal growth factor receptor IC50 = 2.6 nM 8.59 Inhibition of human N-terminal GST-tagged EGFR L858R/T790M double mutant cytopla... 28225269
Epidermal growth factor receptor IC50 = 3.0 nM 8.52 Inhibition of EGFR L858R/T790M mutant (unknown origin) expressed in Sf9 cells pr... 26275028
Epidermal growth factor receptor IC50 = 3.0 nM 8.52 Inhibition of recombinant human GST-tagged EGFR L858R/T790M double mutant expres... 28853575
Epidermal growth factor receptor IC50 = 4.1 nM 8.39 Inhibition of EGFR L858R/T790M mutant phosphorylation in human patient derived H... 27433829
Epidermal growth factor receptor IC50 = 4.19 nM 8.38 Inhibition of EGFR L858R/T790M mutant (unknown origin) incubated for 35 mins by ... 35594654
Epidermal growth factor receptor IC50 = 4.3 nM 8.37 Inhibition of N-terminal 6His/TEV protease cleavage site-tagged human EGFR L858R... 28033579

Literature References

PubMed DOI Target Context # Activities
28225269 10.1021/acs.jmedchem.6b01626 Epidermal growth factor receptor 15
26275028 10.1021/acs.jmedchem.5b01082 Epidermal growth factor receptor 9
26968253 10.1016/j.bmcl.2016.02.067 Epidermal growth factor receptor 9
28526474 10.1016/j.ejmech.2017.05.027 Homo sapiens 6
26756222 10.1021/acs.jmedchem.5b01633 Epidermal growth factor receptor 6
29191878 10.1126/science.aan4368 Unchecked 5
36423823 10.1016/j.bmcl.2022.129084 Unchecked 4
28287730 10.1021/acs.jmedchem.6b01894 Epidermal growth factor receptor 4
- 10.1039/C5MD00208G Epidermal growth factor receptor 4
27634676 10.1016/j.bmc.2016.09.001 NON-PROTEIN TARGET 4
28282122 10.1021/acs.jmedchem.6b01907 Epidermal growth factor receptor 4
26968253 10.1016/j.bmcl.2016.02.067 NON-PROTEIN TARGET 3
27433829 10.1021/acs.jmedchem.5b01985 Epidermal growth factor receptor 3
28853575 10.1021/acs.jmedchem.7b00515 ADMET 3
28853575 10.1021/acs.jmedchem.7b00515 Epidermal growth factor receptor 3
28853575 10.1021/acs.jmedchem.7b00515 Plasma 3
28853575 10.1021/acs.jmedchem.7b00515 No relevant target 2
26756222 10.1021/acs.jmedchem.5b01633 ADMET 2
27634676 10.1016/j.bmc.2016.09.001 Epidermal growth factor receptor 2
28853575 10.1021/acs.jmedchem.7b00515 Unchecked 2

Data from ChEMBL 36 via Core Engine