Compound Detail

CHEMBL191334

NUTLIN-3

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COc1ccc(C2=N[C@@H](c3ccc(Cl)cc3)[C@@H](c3ccc(Cl)cc3)N2C(=O)N2CCNC(=O)C2)c(OC(C)C)c1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL191334
Name	NUTLIN-3
Phase	Preclinical
Structure Type	MOL
InChI Key	BDUHCSBCVGXTJM-WUFINQPMSA-N

246

Targets

726

Activities

Assay Types

PK Parameters

Publications

Known Names

Molecular Properties

581.5

MW (Da)

5.89

ALogP

HBA

HBD

83.5

PSA (Å²)

0.39

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Availability	Unknown
Chirality	Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula	C30H30Cl2N4O4
MW	581.50
Aromatic Rings	3
Heavy Atoms	40
NP-Likeness	-0.25

Activity Summary

IC50 688 meas. best 8.46

Ki 27 meas. best 8.19

Kd 9 meas. best 7.7

EC50 2 meas. best 5.38

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
Tumour suppressor p53/oncoprotein Mdm2 CHEMBL1907611	IC50	8.46	7.1615	3.5	20
NCI-H460 CHEMBL396	IC50	8.19	6.3867	6.5	3
E3 ubiquitin-protein ligase Mdm2 CHEMBL5023	Ki	8.19	7.0436	6.4	14
Tumour suppressor protein p53/Mdm4 CHEMBL2221344	IC50	8.03	5.795	9.3	4
E3 ubiquitin-protein ligase Mdm2 CHEMBL5023	IC50	8.0	6.7732	10.0	22
E3 ubiquitin-protein ligase Mdm2 CHEMBL3600278	Ki	7.98	7.98	10.5	1
Unchecked CHEMBL612545	Ki	7.9	6.84	12.6	2
E3 ubiquitin-protein ligase Mdm2 CHEMBL3600279	Ki	7.7	7.7	19.9	1
E3 ubiquitin-protein ligase Mdm2 CHEMBL5023	Kd	7.7	7.036	20.0	5
SW480 CHEMBL612544	IC50	7.62	5.7033	24.1	3
HeLa CHEMBL399	IC50	7.55	5.5367	28.2	3
Tumour suppressor p53/oncoprotein Mdm2 CHEMBL1907611	Ki	7.37	7.034	42.6	5
Unchecked CHEMBL612545	IC50	7.05	6.9	90.0	3
MOLM-13 CHEMBL3706572	IC50	6.7	6.7	199.0	1
MV4-11 CHEMBL613835	IC50	6.21	6.21	612.4	1
H4 CHEMBL1075452	IC50	6.18	6.18	662.8	1
SJSA-1 CHEMBL2366298	IC50	6.16	5.8483	700.0	6
PA-1 CHEMBL614949	IC50	6.06	6.06	871.0	1
NON-PROTEIN TARGET CHEMBL3879801	IC50	6.0	5.0544	1000.0	9
Cellular tumor antigen p53 CHEMBL4096	IC50	6.0	5.67	1000.0	3
RKO CHEMBL614879	IC50	6.0	5.718	1000.0	5
MSTO-211H CHEMBL1075509	IC50	5.99	5.71	1028.0	3
NKM-1 CHEMBL2366133	IC50	5.98	5.98	1049.3	1
HCT-116 CHEMBL394	IC50	5.98	5.5345	1038.0	11
NEC8 CHEMBL2366340	IC50	5.92	5.92	1215.7	1
EOL1 CHEMBL614489	IC50	5.9	5.9	1267.0	1
K5 CHEMBL2366152	IC50	5.85	5.85	1420.7	1
ADMET CHEMBL612558	IC50	5.85	5.85	1400.0	1
Protein Mdm4 CHEMBL1255126	Ki	5.8	4.98	1599.0	2
Tumour suppressor protein p53/Mdm4 CHEMBL2221344	Ki	5.8	5.515	1599.0	2
QIMR-WIL CHEMBL2366337	IC50	5.79	5.79	1608.5	1
MOLT-16 CHEMBL2366362	IC50	5.75	5.75	1786.0	1
CHP-212 CHEMBL1075423	IC50	5.74	5.74	1813.7	1
A549 CHEMBL392	IC50	5.73	5.2533	1881.0	9
CTB-1 CHEMBL2366344	IC50	5.69	5.69	2022.5	1
HepG2 CHEMBL395	IC50	5.69	5.3233	2051.0	3
A101D CHEMBL2366306	IC50	5.63	5.63	2350.1	1
MOLT-4 CHEMBL614177	IC50	5.63	5.63	2328.5	1
DOHH-2 CHEMBL2366181	IC50	5.62	5.62	2422.8	1
ES4 CHEMBL2366118	IC50	5.61	5.61	2431.6	1
SW780 CHEMBL1075595	IC50	5.6	5.6	2508.8	1
VA-ES-BJ CHEMBL2366259	IC50	5.59	5.59	2541.1	1
RPMI-8866 CHEMBL2366341	IC50	5.59	5.59	2562.1	1
JVM-3 CHEMBL2366372	IC50	5.59	5.59	2593.2	1
ML-2 CHEMBL614356	IC50	5.59	5.59	2565.8	1
DK-MG CHEMBL1075433	IC50	5.58	5.58	2624.7	1
NB69 CHEMBL1075510	IC50	5.58	5.58	2653.3	1
LNCaP-Clone-FGC CHEMBL2366172	IC50	5.58	5.58	2643.2	1
A3-KAW CHEMBL2366273	IC50	5.58	5.58	2618.2	1
HT-144 CHEMBL2366291	IC50	5.58	5.58	2645.8	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	65000.0	ng.hr.mL-1	Mus musculus
Cmax	20808.25	nM	Mus musculus
Fu	0.118	-	Mus musculus
Fu	0.007	-	Mus musculus
T1/2	2.6	hr	Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
Tumour suppressor p53/oncoprotein Mdm2	IC50	=	3.5	nM	8.46	Inhibition of human MDM2 (1 to 125 residues) and p53 (unknown origin) interactio...	30221935
Tumour suppressor p53/oncoprotein Mdm2	IC50	=	4.1	nM	8.39	Inhibition of MDM2/p53 interaction (unknown origin) using biotinylated MDM2 and ...	26181851
NCI-H460	IC50	=	6.49	nM	8.19	Growth inhibition of human NCI-H460 cells harboring p53 incubated for 4 days by ...	38062557
E3 ubiquitin-protein ligase Mdm2	Ki	=	6.4	nM	8.19	Inhibition of human MDM2 by TR-FRET assay	26181851
Tumour suppressor protein p53/Mdm4	IC50	=	9.3	nM	8.03	Inhibition of GST-tagged MDM4/Biotin-tagged p53 interaction (unknown origin) inc...	35420431
Tumour suppressor p53/oncoprotein Mdm2	IC50	=	10.0	nM	8.0	Inhibition of p53 (18 to 26)-MDM2 (2 to 188) interaction using fluorescent dye C...	22507962
Tumour suppressor p53/oncoprotein Mdm2	IC50	=	10.0	nM	8.0	Inhibition of p53-MDM2 interaction (unknown origin) by TR-FRET assay	26141769
E3 ubiquitin-protein ligase Mdm2	IC50	=	10.0	nM	8.0	Inhibition of Cy5-labeled p53 derived TFSDLWKLL peptide binding to C-terminal bi...	30217415
Tumour suppressor p53/oncoprotein Mdm2	IC50	=	10.0	nM	8.0	Inhibition of C-terminal biotin-tagged streptavidin labelled human MDM2 ( 2 to 1...	27542305
E3 ubiquitin-protein ligase Mdm2	Ki	=	10.5	nM	7.98	Inhibition of dog MDM2 by TR-FRET assay	26181851
Unchecked	Ki	=	12.6	nM	7.9	Inhibition of rat MDM2 by TR-FRET assay	26181851
Tumour suppressor p53/oncoprotein Mdm2	IC50	=	17.8	nM	7.75	Inhibition of human MDM2-p53 interaction after 18 hrs by HTRF assay	22524527
E3 ubiquitin-protein ligase Mdm2	IC50	=	18.0	nM	7.75	Inhibition of human recombinant GST-thrombin-MDM2 (1 to 188) expressed in Escher...	23597064
Tumour suppressor p53/oncoprotein Mdm2	IC50	=	18.7	nM	7.73	Inhibition of GST-tagged MDM2/Biotin-tagged p53 interaction (unknown origin) inc...	35420431
Tumour suppressor p53/oncoprotein Mdm2	IC50	=	18.7	nM	7.73	Inhibition of human MDM2/p53 interaction by SPR analysis	34286973
E3 ubiquitin-protein ligase Mdm2	IC50	=	18.7	nM	7.73	Antagonist activity against human MDM2 by TR-FRET assay	34286973
E3 ubiquitin-protein ligase Mdm2	Kd	=	20.0	nM	7.7	Binding affinity to MDM2 (unknown origin) assessed as dissociation constant	39185935
E3 ubiquitin-protein ligase Mdm2	Kd	=	20.0	nM	7.7	Binding affinity to GST-tagged human MDM2 extracted from Escherichia coli BL21 (...	39185935
E3 ubiquitin-protein ligase Mdm2	Ki	=	19.9	nM	7.7	Inhibition of mouse MDM2 by TR-FRET assay	26181851
SW480	IC50	=	24.08	nM	7.62	Growth inhibition of human SW480 cells incubated for 4 days by CCK-8 assay	38062557

Literature References

PubMed	DOI	Target Context	# Activities
35420431	10.1021/acs.jmedchem.2c00095	Unchecked	18
16474381	10.1038/nchembio774	MCF7	17
30045621	10.1021/acs.jmedchem.8b00664	A549	16
24852275	10.1016/j.ejmech.2014.05.027	HCT-116	12
20947617	10.1124/dmd.110.035915	ADMET	8
26982372	10.1021/acs.jmedchem.5b01913	Molecular identity unknown	8
23802716	10.1021/jm400311n	MCF7	8
31196710	10.1016/j.bmcl.2019.06.007	Tumour suppressor p53/oncoprotein Mdm2	6
18680271	10.1021/jm8002813	E3 ubiquitin-protein ligase Mdm2	6
23046248	10.1021/jm300969t	A549	5
23540934	10.1021/np400049j	E3 ubiquitin-protein ligase Mdm2	5
26982372	10.1021/acs.jmedchem.5b01913	E3 ubiquitin-protein ligase Mdm2	5
27010502	10.1016/j.bmc.2016.03.021	MCF7	4
21314128	10.1021/jm1011929	E3 ubiquitin-protein ligase Mdm2	4
26982372	10.1021/acs.jmedchem.5b01913	Apoptosis regulator Bcl-2	4
19856920	10.1021/jm900681h	HCT-116	4
29089230	10.1016/j.bmcl.2017.10.049	Tumour suppressor p53/oncoprotein Mdm2	4
31421630	10.1016/j.ejmech.2019.111588	HCT-116	4
26181851	10.1021/acs.jmedchem.5b00810	Unchecked	4
-	10.1039/C5MD00450K	Cellular tumor antigen p53	4

Data from ChEMBL 36 via Core Engine