Compound Detail

CHEMBL3577124

LY-3009120

Phase I

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Phase I

CNc1ncc2cc(-c3cc(NC(=O)NCCC(C)(C)C)c(F)cc3C)c(C)nc2n1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL3577124
Name	LY-3009120
Phase	Phase I
Structure Type	MOL
InChI Key	HHCBMISMPSAZBF-UHFFFAOYSA-N

Known Names

DP-4978 Ly-3009120 LY3009120 Pan-raf inhibitor ly3009120

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

424.5

MW (Da)

5.05

ALogP

HBA

HBD

91.8

PSA (Å²)

0.53

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Chirality	Achiral

Extended Properties

Molecular Formula	C23H29FN6O
MW	424.52
Aromatic Rings	3
Heavy Atoms	31
NP-Likeness	-1.35

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Serine/threonine-protein kinase B-raf inhibitor	INHIBITOR	Serine/threonine-protein kinase B-raf	✓	✓
Serine/threonine-protein kinase RAF inhibitor	INHIBITOR	RAF proto-oncogene serine/threonine-protein kinase	✓	✓
Serine/threonine-protein kinase A-Raf inhibitor	INHIBITOR	Serine/threonine-protein kinase A-Raf	✓	✓

Indications

Carcinoma, Non-Small-Cell Lung Colorectal Neoplasms Melanoma Neoplasm Metastasis

Activity Summary

IC50 46 meas. best 8.92

Ki 4 meas. best 10.21

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
RAF proto-oncogene serine/threonine-protein kinase CHEMBL1906	Ki	10.21	10.21	0.1	2
Serine/threonine-protein kinase B-raf CHEMBL5145	Ki	9.86	9.86	0.1	2
Serine/threonine-protein kinase A-Raf CHEMBL1169596	IC50	8.92	7.88	1.2	3
Serine/threonine-protein kinase B-raf CHEMBL5145	IC50	8.82	7.8875	1.5	8
RAF proto-oncogene serine/threonine-protein kinase CHEMBL1906	IC50	8.42	7.8875	3.8	4
A-375 CHEMBL613859	IC50	8.04	7.415	9.2	4
Ephrin type-A receptor 2 CHEMBL2068	IC50	7.7	7.7	20.0	1
Mitogen-activated protein kinase kinase kinase 20 CHEMBL3886	IC50	7.41	7.41	39.0	1
A549 CHEMBL392	IC50	7.34	6.8	45.6	4
MAP kinase p38 CHEMBL2094115	IC50	7.21	7.21	61.0	1
Tyrosine-protein kinase Fyn CHEMBL1841	IC50	7.04	7.04	91.0	1
Mitogen-activated protein kinase kinase kinase 1 CHEMBL3956	IC50	7.01	7.01	98.0	1
MV4-11 CHEMBL613835	IC50	7.0	7.0	100.0	1
Ephrin type-B receptor 4 CHEMBL5147	IC50	7.0	7.0	100.0	1
GTPase KRas CHEMBL2189121	IC50	6.82	6.82	150.0	1
SK-MEL-2 CHEMBL614917	IC50	6.7	6.7	200.0	1
HCT-116 CHEMBL394	IC50	6.66	6.66	220.0	1
Tyrosine-protein kinase CSK CHEMBL2634	IC50	6.54	6.54	290.0	1
Proto-oncogene tyrosine-protein kinase Src CHEMBL267	IC50	6.51	6.51	310.0	1
Tyrosine-protein kinase ABL1 CHEMBL1862	IC50	6.42	6.42	380.0	1
Interleukin-1 receptor-associated kinase 1 CHEMBL3357	IC50	6.41	6.41	390.0	1
eIF-2-alpha kinase GCN2 CHEMBL5358	IC50	6.35	6.35	450.0	1
c-Jun N-terminal kinase, JNK CHEMBL2096667	IC50	6.33	6.33	470.0	1
Dual specificity mitogen-activated protein kinase kinase 5 CHEMBL4948	IC50	6.1	6.1	800.0	1
Unchecked CHEMBL612545	IC50	6.05	6.05	900.0	1
HT-29 CHEMBL384	IC50	6.05	6.05	900.0	1
Mitogen-activated protein kinase kinase kinase kinase 5 CHEMBL4852	IC50	6.01	6.01	970.0	1
HepG2 CHEMBL395	IC50	5.58	5.58	2600.0	1
Vascular endothelial growth factor receptor 2 CHEMBL279	IC50	5.41	5.41	3900.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	169.0	ng.hr.mL-1	Rattus norvegicus
AUC	1667.0	ng.hr.mL-1	Rattus norvegicus
AUC	20.5	ng.hr.mL-1	Canis lupus familiaris
AUC	2093.0	ng.hr.mL-1	Canis lupus familiaris
AUC	1260.0	ng.hr.mL-1	Macaca mulatta
CL	34.1	mL.min-1.kg-1	Rattus norvegicus
CL	14.6	mL.min-1.kg-1	Canis lupus familiaris
CL	25.9	mL.min-1.kg-1	Macaca mulatta
CL	30.0	%	Rattus norvegicus
CL	30.0	%	Canis lupus familiaris
CL	30.0	%	Macaca mulatta
Cmax	81.03	nM	Rattus norvegicus
Cmax	932.82	nM	Rattus norvegicus
Cmax	6.596	nM	Canis lupus familiaris
Cmax	1203.71	nM	Canis lupus familiaris
Cmax	1158.96	nM	Macaca mulatta
F	3.6	%	Rattus norvegicus
F	31.7	%	Rattus norvegicus
F	0.2	%	Canis lupus familiaris
F	16.7	%	Canis lupus familiaris
F	20.0	%	Macaca mulatta
T1/2	1.4	hr	Rattus norvegicus
T1/2	2.7	hr	Rattus norvegicus
T1/2	7.6	hr	Canis lupus familiaris
T1/2	7.9	hr	Canis lupus familiaris
T1/2	3.5	hr	Macaca mulatta
T1/2	1.1	hr	Rattus norvegicus
T1/2	1.8	hr	Canis lupus familiaris
T1/2	1.0	hr	Macaca mulatta
T1/2	67.0	hr	Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
RAF proto-oncogene serine/threonine-protein kinase	Ki	=	0.061	nM	10.21	Inhibition of CRAF Y340D/Y341D mutant (unknown origin) using inactive MAP2K1 as ...	33780623
RAF proto-oncogene serine/threonine-protein kinase	Ki	=	0.061	nM	10.21	Inhibition of CRAF Y340D/Y341D mutant (unknown origin) assessed as using inactiv...	34055227
Serine/threonine-protein kinase B-raf	Ki	=	0.139	nM	9.86	Inhibition of BRAF (unknown origin) (416 to 766) inactive MAP2K1 as substrate pr...	33780623
Serine/threonine-protein kinase B-raf	Ki	=	0.139	nM	9.86	Inhibition of BRAF (unknown origin) (416 to 766) assessed as using inactive phos...	34055227
Serine/threonine-protein kinase A-Raf	IC50	=	1.2	nM	8.92	Inhibition of ARaf (unknown origin)	30529543
Serine/threonine-protein kinase B-raf	IC50	=	1.5	nM	8.82	Inhibition of BRAF (unknown origin)	30529543
RAF proto-oncogene serine/threonine-protein kinase	IC50	=	3.8	nM	8.42	Inhibition of cRAF (unknown origin)	30529543
RAF proto-oncogene serine/threonine-protein kinase	IC50	=	4.3	nM	8.37	Inhibition of wild type CRAF (unknown origin) assessed as ADP formation measured...	25965804
Serine/threonine-protein kinase B-raf	IC50	=	5.5	nM	8.26	Inhibition of human GST-tagged BRAF V600E mutant (416 to 766 residues) using hum...	30529543
Serine/threonine-protein kinase B-raf	IC50	=	5.8	nM	8.24	Inhibition of recombinant BRAF V600E mutant (unknown origin) assessed as ADP for...	25965804
A-375	IC50	=	9.2	nM	8.04	Antiproliferative activity against human A375 cells after 72 hrs by resazurin as...	25965804
Serine/threonine-protein kinase B-raf	IC50	=	15.0	nM	7.82	Inhibition of wild type BRAF (unknown origin) assessed as ADP formation measured...	25965804
Ephrin type-A receptor 2	IC50	=	20.0	nM	7.7	Competitive binding affinity to EphA2 in human A375 cells after 15 mins in prese...	25965804
A-375	IC50	=	28.3	nM	7.55	Antiproliferative activity against human A375 cells harboring BRAF mutant assess...	34055227
A-375	IC50	=	28.3	nM	7.55	Antiproliferative activity against human A-375 cells harboring BRAF mutant asses...	33780623
Serine/threonine-protein kinase B-raf	IC50	=	31.0	nM	7.51	Inhibition of BRAF (unknown origin)	32340792
Serine/threonine-protein kinase B-raf	IC50	=	31.0	nM	7.51	Competitive binding affinity to BRAF in human A375 cells after 15 mins in presen...	25965804
Serine/threonine-protein kinase B-raf	IC50	=	31.0	nM	7.51	Inhibition of desthiobiotin-ATP acylphosphate probe binding to B-Raf in human A3...	30529543
Serine/threonine-protein kinase B-raf	IC50	=	37.0	nM	7.43	Inhibition of BRAF V600E mutant in human A375 cells assessed as inhibition of ER...	25965804
Mitogen-activated protein kinase kinase kinase 20	IC50	=	39.0	nM	7.41	Competitive binding affinity to ZAK in human A375 cells after 15 mins in presenc...	25965804

Literature References

PubMed	DOI	Target Context	# Activities
25965804	10.1021/acs.jmedchem.5b00067	Rattus norvegicus	15
25965804	10.1021/acs.jmedchem.5b00067	Canis familiaris	12
25965804	10.1021/acs.jmedchem.5b00067	Rhesus monkey	8
25965804	10.1021/acs.jmedchem.5b00067	ADMET	4
-	10.6019/CHEMBL4495565	SARS-CoV-2	4
25965804	10.1021/acs.jmedchem.5b00067	Serine/threonine-protein kinase B-raf	4
30529543	10.1016/j.ejmech.2018.11.033	Serine/threonine-protein kinase B-raf	3
25965804	10.1021/acs.jmedchem.5b00067	No relevant target	3
-	10.6019/CHEMBL5724709	HEK-293T	2
-	10.6019/CHEMBL4495564	Replicase polyprotein 1ab	2
30529543	10.1016/j.ejmech.2018.11.033	RAF proto-oncogene serine/threonine-protein kinase	2
33780623	10.1021/acs.jmedchem.0c02085	A549	2
-	10.6019/CHEMBL5724709	Fibroblast	2
34055227	10.1021/acsmedchemlett.1c00063	A549	2
-	10.6019/CHEMBL4808148	Histone deacetylase 6	2
25965804	10.1021/acs.jmedchem.5b00067	Molecular identity unknown	2
-	10.6019/CHEMBL5724709	U2OS	2
30529543	10.1016/j.ejmech.2018.11.033	Serine/threonine-protein kinase A-Raf	2
25965804	10.1021/acs.jmedchem.5b00067	RAF proto-oncogene serine/threonine-protein kinase	2
25965804	10.1021/acs.jmedchem.5b00067	Mitogen-activated protein kinase kinase kinase 1	1

Data from ChEMBL 36 via Core Engine