Compound Detail

CHEMBL1231160

PEVONEDISTAT

🧪 Phase III

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🧪 Phase III

NS(=O)(=O)OC[C@@H]1C[C@@H](n2ccc3c(N[C@H]4CCc5ccccc54)ncnc32)C[C@@H]1O

ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID	CHEMBL1231160
Name	PEVONEDISTAT
Phase	Phase III
Structure Type	MOL
InChI Key	MPUQHZXIXSTTDU-QXGSTGNESA-N

Known Names

MLN 4924 MLN-4924 MLN-4924003 MLN4924 Pevonedistat

Targets

Activities

Assay Types

PK Parameters

Publications

Known Names

Indications

Mechanisms

Molecular Properties

443.5

MW (Da)

2.06

ALogP

HBA

HBD

132.4

PSA (Å²)

0.53

QED

Ro5 Violations

Rot. Bonds

Drug Information

Molecule Type	Small molecule
Chirality	Single Enantiomer

Flags

Natural Product Chemical Probe

USAN Stem	-stat
USAN Year	2012

Extended Properties

Molecular Formula	C21H25N5O4S
MW	443.53
Aromatic Rings	3
Heavy Atoms	31
NP-Likeness	-0.13

Mechanism of Action

Mechanism	Action Type	Target	Direct	Efficacy
NEDD8 activating enzyme inhibitor	INHIBITOR	NEDD8 activating enzyme	✓	✓

Indications

Leukemia, Myeloid, Acute Carcinoma, Hepatocellular Carcinoma, Non-Small-Cell Lung Cholangiocarcinoma Leukemia, Myelomonocytic, Chronic Myelodysplastic Syndromes Hematologic Neoplasms Leukemia Lymphoma, Follicular Lymphoma, Large B-Cell, Diffuse Melanoma Mesothelioma Multiple Myeloma Neoplasms Neoplasms Precursor Cell Lymphoblastic Leukemia-Lymphoma

Activity Summary

IC50 49 meas. best 9.59

EC50 3 meas. best 7.52

Target Activity Profile

Target	Type	Best pChEMBL	Mean pChEMBL	Best (nM)	# Data
NEDD8 activating enzyme CHEMBL3831283	IC50	9.59	8.7967	0.3	3
Unchecked CHEMBL612545	IC50	8.43	7.3533	3.7	3
NEDD8-activating enzyme E1 regulatory subunit CHEMBL2016431	IC50	8.4	7.85	4.0	3
Proteasome CHEMBL612443	IC50	8.4	8.4	4.0	1
NEDD8 CHEMBL4295831	IC50	8.33	8.33	4.7	1
NEDD8-activating enzyme E1 catalytic subunit CHEMBL2016430	IC50	8.3	8.3	5.0	1
NEDD8 activating enzyme CHEMBL3831283	EC50	7.52	6.495	30.0	2
HCT-116 CHEMBL394	IC50	7.47	7.21	33.9	3
HuTu80 CHEMBL614582	IC50	7.37	7.37	42.6	1
LNCaP-Clone-FGC CHEMBL2366172	IC50	7.19	7.19	64.6	1
CAPAN-1 CHEMBL614536	IC50	7.0	7.0	101.0	1
MV4-11 CHEMBL613835	IC50	6.97	6.97	107.0	1
K562 CHEMBL385	EC50	6.97	6.97	108.0	1
THP-1 CHEMBL614245	IC50	6.94	6.94	115.0	1
Jurkat CHEMBL397	IC50	6.82	6.82	152.0	1
U2OS CHEMBL615023	IC50	6.8	6.8	160.0	1
RKO CHEMBL614879	IC50	6.78	6.78	166.0	1
DU-145 CHEMBL613508	IC50	6.7	6.7	201.0	1
HepG2 CHEMBL395	IC50	6.52	5.805	300.0	2
EKVX CHEMBL614487	IC50	6.52	6.52	300.0	1
T47D CHEMBL614361	IC50	6.52	6.52	300.0	1
NCI-H1299 CHEMBL612255	IC50	6.52	6.415	300.0	2
MCF7 CHEMBL387	IC50	6.52	6.52	300.0	1
PLC CHEMBL613522	IC50	6.52	6.52	300.0	1
Huh-7 CHEMBL614039	IC50	6.52	6.52	300.0	1
MKN-45 CHEMBL614354	IC50	6.52	6.52	300.0	1
MGC-803 CHEMBL3706566	IC50	6.52	5.85	300.0	3
HT-29 CHEMBL384	IC50	6.32	6.32	484.0	1
A549 CHEMBL392	IC50	6.2	5.4367	630.0	3
BEAS-2B CHEMBL4296403	IC50	5.91	5.91	1220.0	1
HGC-27 CHEMBL1075463	IC50	5.9	5.9	1250.0	1
Ubiquitin-like modifier-activating enzyme 1 CHEMBL5169143	IC50	5.82	5.82	1500.0	1
Ubiquitin-like modifier-activating enzyme 6 CHEMBL2321622	IC50	5.75	5.75	1800.0	1
KYSE-30 CHEMBL4513130	IC50	5.43	5.43	3750.0	1
Caco-2 CHEMBL614058	IC50	5.36	5.36	4400.0	1
SUMO-activating enzyme CHEMBL2095174	IC50	5.09	5.09	8200.0	1
GES1 CHEMBL4296415	IC50	4.87	4.87	13450.0	1

Pharmacokinetic Data

Parameter	Value	Units	Species
AUC	1328.0	ng.hr.mL-1	Rattus norvegicus
AUC	1341.0	ng.hr.mL-1	Rattus norvegicus
CL	16.5	mL.min-1.kg-1	Rattus norvegicus
MRT	1.9	hr	Rattus norvegicus
T1/2	1.36	hr	Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target	Type	Rel.	Value	Units	pChEMBL	Assay	PubMed
NEDD8 activating enzyme	IC50	=	0.26	nM	9.59	Inhibition of NAE (unknown origin) mediated neddylation assessed as decrease in ...	33857374
Unchecked	IC50	=	3.72	nM	8.43	Inhibition of UAE (unknown origin) mediated neddylation assessed as decrease in ...	33857374
NEDD8 activating enzyme	IC50	=	4.0	nM	8.4	Inhibition of NAE1/UBA3 in human HCT-116 cells assessed as reduction in Ubc12-NE...	35131538
Proteasome	IC50	=	4.0	nM	8.4	Inhibition of proteasome (unknown origin)	34974338
NEDD8 activating enzyme	IC50	=	4.0	nM	8.4	Inhibition of NAE (unknown origin)	33857374
NEDD8-activating enzyme E1 regulatory subunit	IC50	=	4.0	nM	8.4	Inhibition of NAE (unknown origin)	38214982
NEDD8-activating enzyme E1 regulatory subunit	IC50	=	4.0	nM	8.4	Inhibition of NAE (unknown origin)	38320715
NEDD8	IC50	=	4.7	nM	8.33	Inhibition of NEDD8 (unknown origin) assessed as decrease in formation of E2-UBL...	28505447
NEDD8-activating enzyme E1 catalytic subunit	IC50	=	5.0	nM	8.3	Inhibition of human recombinant His-tagged NAE1 expressed in baculovirus express...	29547696
Unchecked	IC50	=	5.8	nM	8.24	Inhibition of His-tagged recombinant human NAE expressed in Escherichia coli (BL...	37651876
NEDD8 activating enzyme	EC50	=	30.0	nM	7.52	Inhibition of NAE in human HCT-116 cells incubated for 1 hr by Western blot anal...	33857374
HCT-116	IC50	=	33.89	nM	7.47	Antiproliferative activity against human HCT-116 cells assessed as cell growth i...	33857374
HCT-116	IC50	=	36.2	nM	7.44	Antiproliferative activity against human HCT-116 cells assessed as cell growth i...	33857374
HuTu80	IC50	=	42.6	nM	7.37	Antiproliferative activity against human HuTu80 cells assessed as cell growth in...	33857374
LNCaP-Clone-FGC	IC50	=	64.6	nM	7.19	Antiproliferative activity against human LNCaP-Clone-FGC cells assessed as cell ...	33857374
CAPAN-1	IC50	=	101.0	nM	7.0	Antiproliferative activity against human CAPAN-1 cells assessed as cell growth i...	33857374
MV4-11	IC50	=	107.0	nM	6.97	Antiproliferative activity against human MV4-11 cells assessed as cell growth in...	33857374
K562	EC50	=	108.0	nM	6.97	Antiproliferative activity against human K562 cells after 72 hrs by CellTiter-Gl...	24900352
THP-1	IC50	=	115.0	nM	6.94	Antiproliferative activity against human THP-1 cells assessed as cell growth inh...	33857374
Jurkat	IC50	=	152.0	nM	6.82	Antiproliferative activity against human Jurkat cells assessed as cell growth in...	33857374

Literature References

PubMed	DOI	Target Context	# Activities
33857374	10.1021/acs.jmedchem.1c00242	ADMET	7
31157974	10.1021/acs.jmedchem.9b00003	DCN1-like protein 1/NEDD8-conjugating enzyme Ubc12	6
29232579	10.1016/j.ejmech.2017.11.101	Caco-2	5
30803229	10.1021/acs.jmedchem.9b00113	Unchecked	5
33756127	10.1016/j.ejmech.2021.113326	DCN1-like protein 1	4
33857374	10.1021/acs.jmedchem.1c00242	NEDD8 activating enzyme	3
29232579	10.1016/j.ejmech.2017.11.101	NEDD8 activating enzyme	3
33857374	10.1021/acs.jmedchem.1c00242	HCT-116	3
31732254	10.1016/j.ejmech.2019.111848	HepG2	2
24900352	10.1021/ml2000615	Unchecked	2
31732254	10.1016/j.ejmech.2019.111848	Huh-7	2
31732254	10.1016/j.ejmech.2019.111848	T47D	2
31732254	10.1016/j.ejmech.2019.111848	MCF7	2
31732254	10.1016/j.ejmech.2019.111848	MGC-803	2
31732254	10.1016/j.ejmech.2019.111848	PLC	2
33129593	10.1016/j.ejmech.2020.112964	A549	2
-	10.6019/CHEMBL4808148	Histone deacetylase 6	2
31732254	10.1016/j.ejmech.2019.111848	EKVX	2
33129593	10.1016/j.ejmech.2020.112964	NEDD8-activating enzyme E1 regulatory subunit	2
31732254	10.1016/j.ejmech.2019.111848	A549	2

Data from ChEMBL 36 via Core Engine