Compound Detail

CHEMBL3125702

NAVTEMADLIN

🧪 Phase III

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🧪 Phase III

CC(C)[C@@H](CS(=O)(=O)C(C)C)N1C(=O)[C@@](C)(CC(=O)O)C[C@H](c2cccc(Cl)c2)[C@H]1c1ccc(Cl)cc1

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL3125702
Name	NAVTEMADLIN
Phase	Phase III
Structure Type	MOL
InChI Key	DRLCSJFKKILATL-YWCVFVGNSA-N

Known Names

Amg 232 AMG-232 Krt-232 Mdm2 inhibitor amg-232 Navtemadlin

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

568.6

MW (Da)

6.38

ALogP

HBA

HBD

91.8

PSA (Å²)

0.38

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Chirality	Single Enantiomer

Flags

Chemical Probe

USAN Stem	-madlin
USAN Year	2022

Extended Properties

Molecular Formula	C28H35Cl2NO5S
MW	568.56
Aromatic Rings	2
Heavy Atoms	37
NP-Likeness	-0.45

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
Tumour suppressor p53/oncoprotein Mdm2 inhibitor	INHIBITOR	Tumour suppressor p53/oncoprotein Mdm2	✓	✓

Indications

Endometrial Neoplasms Polycythemia Vera Primary Myelofibrosis Primary Myelofibrosis Small Cell Lung Carcinoma Thrombocythemia, Essential Carcinoma, Merkel Cell Carcinoma, Non-Small-Cell Lung Gliosarcoma Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid, Acute Melanoma Multiple Myeloma Myeloproliferative Disorders Neoplasms Neoplasms Plasmacytoma Sarcoma

Activity Summary

IC50 16 meas. best 9.22

Kd 3 meas. best 10.42

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
E3 ubiquitin-protein ligase Mdm2 CHEMBL5023	Kd	10.42	10.3733	0.0	3
Tumour suppressor p53/oncoprotein Mdm2 CHEMBL1907611	IC50	9.22	9.1467	0.6	3
E3 ubiquitin-protein ligase Mdm2 CHEMBL5023	IC50	9.22	8.794	0.6	5
Hepatocyte CHEMBL613690	IC50	8.2	8.2	6.3	1
SJSA-1 CHEMBL2366298	IC50	8.04	7.8933	9.1	3
HCT-116 CHEMBL394	IC50	8.0	8.0	10.0	1
CWR22R CHEMBL612657	IC50	6.52	6.52	300.0	1
A-375 CHEMBL613859	IC50	6.22	6.22	600.0	1
Unchecked CHEMBL612545	IC50	6.05	6.05	900.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
CL	8.5	mL.min-1.kg-1	Macaca fascicularis
CL	11.0	mL.min-1.kg-1	Rattus norvegicus
CL	8.5	mL.min-1.kg-1	Macaca fascicularis
CL	0.25	mL.min-1.kg-1	Rattus norvegicus
CL	0.25	mL.min-1.kg-1	Mus musculus
CL	0.25	mL.min-1.kg-1	Macaca fascicularis
F	51.0	%	Macaca fascicularis
F	51.0	%	Macaca fascicularis
F	42.0	%	Rattus norvegicus
F	43.0	%	Mus musculus
F	44.0	%	Macaca fascicularis
F	18.0	%	Canis lupus familiaris
T1/2	2.4	hr	Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
E3 ubiquitin-protein ligase Mdm2	Kd	=	0.038	nM	10.42	Binding affinity to human MDM2 by by isothermal titration calorimetry	25384157
E3 ubiquitin-protein ligase Mdm2	Kd	=	0.045	nM	10.35	Binding affinity to human MDM2 by by surface plasmon resonace spectroscopy	25384157
E3 ubiquitin-protein ligase Mdm2	Kd	=	0.045	nM	10.35	Binding affinity to human MDM2 by by Surface Plasmon Resonace (SPR) spectroscopy...	24456472
E3 ubiquitin-protein ligase Mdm2	IC50	=	0.6	nM	9.22	Inhibition of MDM2 (unknown origin)	31128449
Tumour suppressor p53/oncoprotein Mdm2	IC50	=	0.6	nM	9.22	Inhibition of MDM2/ P53 (unknown origin) interaction	33423841
Tumour suppressor p53/oncoprotein Mdm2	IC50	=	0.6	nM	9.22	Inhibition of human MDM2/p53 interaction by HTRF based biochemical assay	35420431
E3 ubiquitin-protein ligase Mdm2	IC50	=	0.6	nM	9.22	Binding affinity to human GST-thrombin-tagged MDM2 assessed as inhibition of int...	24456472
E3 ubiquitin-protein ligase Mdm2	IC50	=	0.63	nM	9.2	Binding affinity to human GST-thrombin-tagged MDM2 ( 1 to 188 aa) assessed as in...	25384157
Tumour suppressor p53/oncoprotein Mdm2	IC50	=	1.0	nM	9.0	Homogenous Time-Resolved Fluorescence Assay (HTRF2 Assay): The standard assay co...	-
E3 ubiquitin-protein ligase Mdm2	IC50	=	1.0	nM	9.0	Homogenous Time-Resolved Fluorescence Assay (HTRF2 Assay): The standard assay co...	-
Hepatocyte	IC50	=	6.3	nM	8.2	Intrinsic clearance in human hepatocytes measured per million cells	25384157
SJSA-1	IC50	=	9.1	nM	8.04	Antiproliferative activity against human SJSA1 cells assessed as inhibition of E...	24456472
SJSA-1	IC50	=	9.2	nM	8.04	Antiproliferative activity against human SJSA1 cells assessed as inhibition of E...	25384157
HCT-116	IC50	=	10.0	nM	8.0	Antiproliferative activity against human HCT116 cells expressing p53 wild type a...	24456472
SJSA-1	IC50	=	25.0	nM	7.6	Antiproliferative activity against human SJSA-1 cells	33423841
E3 ubiquitin-protein ligase Mdm2	IC50	=	47.0	nM	7.33	Binding affinity to MDM2 in human SJSA1 cells assessed as induction of p21 gene ...	25384157
CWR22R	IC50	=	300.0	nM	6.52	Antiproliferative activity against human 22Rv1 cells assessed as inhibition of c...	37130471
A-375	IC50	=	600.0	nM	6.22	Antiproliferative activity against human A-375 cells assessed as inhibition of c...	37130471
Unchecked	IC50	=	900.0	nM	6.05	Antiproliferative activity against human EU-1 cells assessed as inhibition of ce...	37130471

Literature References

PubMed	DOI	Target Context	# Activities
35429910	10.1016/j.ejmech.2022.114334	ADMET	6
24601644	10.1021/jm401911v	ADMET	5
24456472	10.1021/jm401753e	SJSA-1	4
25384157	10.1021/jm501550p	ADMET	4
25384157	10.1021/jm501550p	E3 ubiquitin-protein ligase Mdm2	4
24456472	10.1021/jm401753e	Mus musculus	3
32738747	10.1016/j.bmcl.2020.127424	Unchecked	3
29691156	10.1016/j.bmc.2018.04.036	HCT-116	3
-	10.6019/CHEMBL4495565	SARS-CoV-2	2
30253242	10.1016/j.ejmech.2018.09.044	Cynomolgus monkey	2
-	10.6019/CHEMBL4808148	Histone deacetylase 6	2
35429910	10.1016/j.ejmech.2022.114334	Hepatocyte	2
24456472	10.1021/jm401753e	E3 ubiquitin-protein ligase Mdm2	2
24456472	10.1021/jm401753e	Rattus norvegicus	2
24456472	10.1021/jm401753e	Cynomolgus monkey	2
24456472	10.1021/jm401753e	HCT-116	2
25384157	10.1021/jm501550p	SJSA-1	1
37130471	10.1016/j.ejmech.2023.115423	E3 ubiquitin-protein ligase Mdm2	1
24456472	10.1021/jm401753e	Cytochrome P450 3A4	1
30253242	10.1016/j.ejmech.2018.09.044	SJSA-1	1

Data from ChEMBL 36 via Core Engine