PEVONEDISTAT

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H25N5O4S
Molecular Weight	443.519
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NS(=O)(=O)OC[C@@H]1C[C@H](C[C@@H]1O)N2C=CC3=C(N[C@H]4CCC5=CC=CC=C45)N=CN=C23

InChI

InChIKey=MPUQHZXIXSTTDU-QXGSTGNESA-N

InChI=1S/C21H25N5O4S/c22-31(28,29)30-11-14-9-15(10-19(14)27)26-8-7-17-20(23-12-24-21(17)26)25-18-6-5-13-3-1-2-4-16(13)18/h1-4,7-8,12,14-15,18-19,27H,5-6,9-11H2,(H2,22,28,29)(H,23,24,25)/t14-,15+,18-,19-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C21H25N5O4S
Molecular Weight	443.519
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://investor.millennium.com/phoenix.zhtml?c=80159&p=irol-newsArticle&ID=1534354
Curator's Comment: description was created based on several sources, including

Pevonedistat (MLN4924), discovered by Millennium, is a small molecule inhibitor of the NEDD8-Activating Enzyme (NAE), a key component of the protein homeostasis pathway. MLN4924 is a mechanism-based inhibitor of NAE and creates a covalent NEDD8-MLN4924 adduct catalyzed by the enzyme. The NEDD8-MLN4924 adduct resembles NEDD8 adenylate, the first intermediate in the NAE reaction cycle, but cannot be further utilized in subsequent intraenzyme reactions. The stability of the NEDD8-MLN4924 adduct within the NAE active site blocks enzyme activity, thereby accounting for the potent inhibition of the NEDD8 pathway by MLN4924. This drug is in phase II clinical trial for the treatment acute myeloid leukemia, chronic myelomonocytic leukemia and myelodysplastic syndromes. In addition in phase I for treatment acute lymphoblastic leukemia. The ability of MLN4924 to cross the blood-brain barrier, its low toxicity, and clinical efficacy in other cancers suggests that this drug is an attractive treatment against glioblastomas.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
NEDD8-activating enzyme E1 catalytic subunit 2 Target ID: CHEMBL2016430 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20129059	Substrate 661

Conditions

Condition	Modality	Highest Phase	Product
Acute lymphoblastic leukemia 27 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27626202	Primary	Phase I 438	Unknown Approved Use Unknown
Myelodysplastic syndromes 61 Sources: https://clinicaltrials.gov/ct2/show/NCT02610777	Primary	Phase II 1147	Unknown Approved Use Unknown
Acute myeloid leukemia 141 Sources: https://clinicaltrials.gov/ct2/show/NCT02610777	Primary	Phase II 1147	Unknown Approved Use Unknown
Leukemia, myelomonocytic, chronic 2 Sources: https://clinicaltrials.gov/ct2/show/NCT02610777	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
1173 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25733005	78 mg/m² 3 times / week multiple, intravenous dose: 78 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PEVONEDISTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
648 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25733005	59 mg/m² 3 times / week multiple, intravenous dose: 59 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PEVONEDISTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1212 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25733005	83 mg/m² 2 times / week multiple, intravenous dose: 83 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PEVONEDISTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2452 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27056178	157 mg/m² 1 times / week multiple, intravenous dose: 157 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PEVONEDISTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3591 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27056178	209 mg/m² 2 times / week multiple, intravenous dose: 209 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PEVONEDISTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
3857 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25733005	78 mg/m² 3 times / week multiple, intravenous dose: 78 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PEVONEDISTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2506 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25733005	59 mg/m² 3 times / week multiple, intravenous dose: 59 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PEVONEDISTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3869 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25733005	83 mg/m² 2 times / week multiple, intravenous dose: 83 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PEVONEDISTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8932 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27056178	157 mg/m² 1 times / week multiple, intravenous dose: 157 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PEVONEDISTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
12300 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27056178	209 mg/m² 2 times / week multiple, intravenous dose: 209 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PEVONEDISTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
12 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25733005	83 mg/m² 2 times / week multiple, intravenous dose: 83 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PEVONEDISTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
10.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27056178	157 mg/m² 1 times / week multiple, intravenous dose: 157 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PEVONEDISTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
10.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27056178	209 mg/m² 2 times / week multiple, intravenous dose: 209 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	PEVONEDISTAT plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
278 mg/m2 2 times / week multiple, intravenous Highest studied dose Dose: 278 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 278 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/27056178	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27056178	Disc. AE: Blood creatinine increased, Blood bilirubin increased... AEs leading to discontinuation/dose reduction: Blood creatinine increased (grade 3, 50%) Blood bilirubin increased (grade 3, 50%) Sources: https://pubmed.ncbi.nlm.nih.gov/27056178
209 mg/m2 2 times / week multiple, intravenous MTD Dose: 209 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 209 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/27056178	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27056178	DLT: Aspartate aminotransferase increased, Brain natriuretic peptide increased... Disc. AE: Acute renal failure, Acute hepatic failure... Dose limiting toxicities: Aspartate aminotransferase increased (grade 1, 9%) Brain natriuretic peptide increased (grade 1, 9%) AEs leading to discontinuation/dose reduction: Acute renal failure (grade 5, 9%) Acute hepatic failure (grade 4, 9%) Sources: https://pubmed.ncbi.nlm.nih.gov/27056178
59 mg/m2 3 times / week multiple, intravenous MTD Dose: 59 mg/m2, 3 times / week Route: intravenous Route: multiple Dose: 59 mg/m2, 3 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/25733005	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25733005	Sources: https://pubmed.ncbi.nlm.nih.gov/25733005
83 mg/m2 2 times / week multiple, intravenous MTD Dose: 83 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 83 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/25733005	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25733005	Sources: https://pubmed.ncbi.nlm.nih.gov/25733005
147 mg/m2 2 times / week multiple, intravenous Studied dose Dose: 147 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 147 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/25733005	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25733005	Disc. AE: Multi-organ failure, Heart failure... AEs leading to discontinuation/dose reduction: Multi-organ failure (grade 5, 33.3%) Heart failure (33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/25733005
157 mg/m2 1 times / week multiple, intravenous Studied dose Dose: 157 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 157 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/27056178	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27056178	DLT: Acute myocarditis, Acute renal failure... Dose limiting toxicities: Acute myocarditis (grade 3, 9%) Acute renal failure (grade 2, 9%) Hyperbilirubinemia (grade 2, 9%) Sources: https://pubmed.ncbi.nlm.nih.gov/27056178
78 mg/m2 3 times / week multiple, intravenous Studied dose Dose: 78 mg/m2, 3 times / week Route: intravenous Route: multiple Dose: 78 mg/m2, 3 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/25733005	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25733005	DLT: Transaminases increased, Sepsis syndrome... Dose limiting toxicities: Transaminases increased (50%) Sepsis syndrome (grade 5, 25%) Multiorgan failure (grade 5, 25%) Sources: https://pubmed.ncbi.nlm.nih.gov/25733005

AEs

AE	Significance	Dose	Population
Blood bilirubin increased	grade 3, 50% Disc. AE	278 mg/m2 2 times / week multiple, intravenous Highest studied dose Dose: 278 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 278 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/27056178	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27056178
Blood creatinine increased	grade 3, 50% Disc. AE	278 mg/m2 2 times / week multiple, intravenous Highest studied dose Dose: 278 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 278 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/27056178	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27056178
Aspartate aminotransferase increased	grade 1, 9% DLT, Disc. AE	209 mg/m2 2 times / week multiple, intravenous MTD Dose: 209 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 209 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/27056178	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27056178
Brain natriuretic peptide increased	grade 1, 9% DLT, Disc. AE	209 mg/m2 2 times / week multiple, intravenous MTD Dose: 209 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 209 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/27056178	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27056178
Acute hepatic failure	grade 4, 9% Disc. AE	209 mg/m2 2 times / week multiple, intravenous MTD Dose: 209 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 209 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/27056178	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27056178
Acute renal failure	grade 5, 9% Disc. AE	209 mg/m2 2 times / week multiple, intravenous MTD Dose: 209 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 209 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/27056178	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27056178
Heart failure	33.3% Disc. AE	147 mg/m2 2 times / week multiple, intravenous Studied dose Dose: 147 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 147 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/25733005	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25733005
Multi-organ failure	grade 5, 33.3% Disc. AE	147 mg/m2 2 times / week multiple, intravenous Studied dose Dose: 147 mg/m2, 2 times / week Route: intravenous Route: multiple Dose: 147 mg/m2, 2 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/25733005	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25733005
Acute renal failure	grade 2, 9% DLT, Disc. AE	157 mg/m2 1 times / week multiple, intravenous Studied dose Dose: 157 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 157 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/27056178	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27056178
Hyperbilirubinemia	grade 2, 9% DLT, Disc. AE	157 mg/m2 1 times / week multiple, intravenous Studied dose Dose: 157 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 157 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/27056178	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27056178
Acute myocarditis	grade 3, 9% DLT, Disc. AE	157 mg/m2 1 times / week multiple, intravenous Studied dose Dose: 157 mg/m2, 1 times / week Route: intravenous Route: multiple Dose: 157 mg/m2, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/27056178	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/27056178
Transaminases increased	50% DLT	78 mg/m2 3 times / week multiple, intravenous Studied dose Dose: 78 mg/m2, 3 times / week Route: intravenous Route: multiple Dose: 78 mg/m2, 3 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/25733005	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25733005
Multiorgan failure	grade 5, 25% DLT, Disc. AE	78 mg/m2 3 times / week multiple, intravenous Studied dose Dose: 78 mg/m2, 3 times / week Route: intravenous Route: multiple Dose: 78 mg/m2, 3 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/25733005	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25733005
Sepsis syndrome	grade 5, 25% DLT, Disc. AE	78 mg/m2 3 times / week multiple, intravenous Studied dose Dose: 78 mg/m2, 3 times / week Route: intravenous Route: multiple Dose: 78 mg/m2, 3 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/25733005	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25733005

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741	P-gp 2052 BCRP 697

Drug as perpetrator

Target	Modality	Activity
P-gp 1932	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363677357	inconclusive [IC50 9.2 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=404904707	no
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=440681667	yes [IC50 21.3174 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=440681667	yes [IC50 8.4866 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/30845347/	major	yes (co-administration study) Comment: Fluconazole and itraconazole increased AUCinf by 11% and 14%. Sources: https://pubmed.ncbi.nlm.nih.gov/30845347/
BCRP 697	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/31972220/	yes
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/30845347/	yes

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY110895	https://www.001chemical.com/chem/search?q=DY110895
1PlusChem LLC	1P008TYZ	https://www.1pchem.com/search?query=1P008TYZ
1PlusChem LLC	1P00GUL4	https://www.1pchem.com/search?query=1P00GUL4
AK Scientific	2557AH	https://aksci.com/item_detail.php?cat=2557AH
AK Scientific	3866AH	https://aksci.com/item_detail.php?cat=3866AH
AK Scientific	SYN5699	https://aksci.com/item_detail.php?cat=SYN5699
AOBIOUS INC	AOB87174	http://aobious.com/aobious/search?search_query=AOB87174
AstaTech	42265	http://astatechinc.com/CPSResult.php?CRNO=42265
Axon MedChem	2038	https://www.axonmedchem.com/product/2038
BLD Pharm	BD306042	http://www.bldpharm.com/search/Search.html?keyword=BD306042
BLD Pharm	BD333041	http://www.bldpharm.com/search/Search.html?keyword=BD333041
Cayman Chemical	15217	http://www.caymanchem.com/app/template/Product.vm/catalog/15217
Chem Scene	CS-0068	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0068
ChemShuttle	101181	https://www.chemshuttle.com/catalogsearch/result/?q=101181
eMolecules	36096548	https://orderbb.emolecules.com/search/#?query=36096548
eMolecules	44811748	https://orderbb.emolecules.com/search/#?query=44811748
eMolecules	44811828	https://orderbb.emolecules.com/search/#?query=44811828
eMolecules	48861233	https://orderbb.emolecules.com/search/#?query=48861233
eMolecules	85147654	https://orderbb.emolecules.com/search/#?query=85147654
eNovation Chemicals	D543558	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D543558&searchbtn.x=0&searchbtn.y=0
eNovation Chemicals	D621180	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D621180&searchbtn.x=0&searchbtn.y=0
Excenen	EX-A1472	http://www.excenen.com/searchresultlist.php?id=EX-A1472
KeyOrganics	AS-17002	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-17002
Matrix Scientific	143816	http://www.matrixscientific.com/143816.html
mcule	MCULE-1970540535	https://mcule.com/MCULE-1970540535/
mcule	MCULE-3321377165	https://mcule.com/MCULE-3321377165/
mcule	MCULE-9218913323	https://mcule.com/MCULE-9218913323/
mcule	MCULE-9409080364	https://mcule.com/MCULE-9409080364/
MedChem Express	HY-10484	https://www.medchemexpress.com/search.html?q=HY-10484&ft=&fa=&fp=
MedChem Express	HY-70062	https://www.medchemexpress.com/search.html?q=HY-70062&ft=&fa=&fp=
Molcore	MC110895	http://www.molcore.com/CatMC110895.html
Molnova	M16509	https://www.molnova.com/en/serch-list.html?keywords=M16509
MolPort	MolPort-035-395-795	https://www.molport.com/shop/molecule-link/MolPort-035-395-795
MolPort	MolPort-038-387-829	https://www.molport.com/shop/molecule-link/MolPort-038-387-829
MolPort	MolPort-039-139-733	https://www.molport.com/shop/molecule-link/MolPort-039-139-733
MolPort	MolPort-044-181-469	https://www.molport.com/shop/molecule-link/MolPort-044-181-469
Ryan Scientific	101-94023	https://ryansci.com/products?q=101-94023&list_q=&search_type=exact
Synthonix	14244	https://synthonix.com/catalogsearch/result/?q=14244
TargetMol	T6332	https://www.targetmol.com/search?keyword=T6332
Tetrahedron	TS86833	http://www.thsci.com/search.do?q=TS86833
Toronto Research Chemicals	M425100	https://www.trc-canada.com/product-detail/?CatNum=M425100

PubMed

Title	Date	PubMed
Rictor Undergoes Glycogen Synthase Kinase 3 (GSK3)-dependent, FBXW7-mediated Ubiquitination and Proteasomal Degradation.	2015-05-29	25897075
Inactivation of SAG E3 ubiquitin ligase blocks embryonic stem cell differentiation and sensitizes leukemia cells to retinoid acid.	2011	22110742
NEDD8-targeting drug MLN4924 elicits DNA rereplication by stabilizing Cdt1 in S phase, triggering checkpoint activation, apoptosis, and senescence in cancer cells.	2010-12-15	21159650
Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics.	2010-12-10	21145461
MLN4924, a NEDD8-activating enzyme inhibitor, is active in diffuse large B-cell lymphoma models: rationale for treatment of NF-{kappa}B-dependent lymphoma.	2010-09-02	20525923
Biochemical and cellular effects of inhibiting Nedd8 conjugation.	2010-07-30	20603103
Inhibition of NEDD8-activating enzyme: a novel approach for the treatment of acute myeloid leukemia.	2010-05-06	20203261
SUMO, Ubiquitin, UBL Proteins: Implications For Human Diseases - Fifth International Conference.	2010-04	20373248
Substrate-assisted inhibition of ubiquitin-like protein-activating enzymes: the NEDD8 E1 inhibitor MLN4924 forms a NEDD8-AMP mimetic in situ.	2010-01-15	20129059
Targeting NEDD8-activated cullin-RING ligases for the treatment of cancer.	2009-06-15	19509147
An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer.	2009-04-09	19360080

Patents

Sample Use Guides

In Vivo Use Guide

Azacitidine 75 mg/m^2, intravenously or subcutaneously, on Days 1 to 5, Days 8 and 9 and pevonedistat 20 mg/m^2, 60-minute (±10) infusion, intravenously, on Days 1, 3, and 5 in 28-day treatment cycles.

Route of Administration: Intravenous

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Mon Mar 31 20:17:15 GMT 2025` Edited by `admin` on `Mon Mar 31 20:17:15 GMT 2025`
Record UNII	S3AZD8D215
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

pevonedistat [INN]

Preferred Name

English

PEVONEDISTAT

Official Name

English

SULFAMIC ACID, ((1S,2S,4R)-4-(4-(((1S)-2,3-DIHYDRO-1H-INDEN-1-YL)AMINO)-7H-PYRROLO(2,3-D)PYRIMIDIN-7-YL)-2-HYDROXYCYCLOPENTYL)METHYL ESTER

Common Name

English

((1S,2S,4R)-4-(4-(((1S)-2,3-DIHYDRO-1H-INDEN-1-YL)AMINO(-7H-PYRROLO(2,3-D)PYRIMIDIN-7-YL)-2-HYDROXYCYCLOPENTYL)METHYL SULFAMATE

Common Name

English

MLN4924

Code

English

PEVONEDISTAT [USAN]

Common Name

English

MLN 4924

Code

English

MLN-4924

Code

English

MLN-4924003

Code

English

Pevonedistat [WHO-DD]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

331310