PEVONEDISTAT

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=C2N=CN=C3N[C@H]4CCC5=C4C=CC=C5

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

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 428	Unknown Approved Use Unknown
Myelodysplastic syndromes 58 Sources: https://clinicaltrials.gov/ct2/show/NCT02610777	Primary	Phase II 1132	Unknown Approved Use Unknown
Acute myeloid leukemia 136 Sources: https://clinicaltrials.gov/ct2/show/NCT02610777	Primary	Phase II 1132	Unknown Approved Use Unknown
Leukemia, myelomonocytic, chronic 2 Sources: https://clinicaltrials.gov/ct2/show/NCT02610777	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
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
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
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
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
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

AUC

Value	Dose	Analyte	Population
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
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
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
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
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

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
10.4 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
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

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 Page: p.442	unhealthy, ADULT n = 2 Health Status: unhealthy Condition: melanoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/27056178 Page: p.442	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 Page: p.442
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 Page: p.442	unhealthy, ADULT n = 11 Health Status: unhealthy Condition: melanoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/27056178 Page: p.442	DLT: Brain natriuretic peptide increased, Aspartate aminotransferase increased... Disc. AE: Acute renal failure, Acute hepatic failure... Dose limiting toxicities: Brain natriuretic peptide increased (grade 1, 9%) Aspartate aminotransferase 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 Page: p.442
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 Page: p.537	unhealthy, ADULT n = 13 Health Status: unhealthy Condition: acute myeloid leukaemia Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/25733005 Page: p.537	Sources: https://pubmed.ncbi.nlm.nih.gov/25733005 Page: p.537
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 Page: p.537	unhealthy, ADULT n = 22 Health Status: unhealthy Condition: acute myeloid leukaemia Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 22 Sources: https://pubmed.ncbi.nlm.nih.gov/25733005 Page: p.537	Sources: https://pubmed.ncbi.nlm.nih.gov/25733005 Page: p.537
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 Page: p.537	unhealthy, ADULT n = 3 Health Status: unhealthy Condition: acute myeloid leukaemia Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/25733005 Page: p.537	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 Page: p.537
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 Page: p.442	unhealthy, ADULT n = 11 Health Status: unhealthy Condition: melanoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/27056178 Page: p.442	DLT: Hyperbilirubinemia, Acute renal failure... Dose limiting toxicities: Hyperbilirubinemia (grade 2, 9%) Acute renal failure (grade 2, 9%) Acute myocarditis (grade 3, 9%) Sources: https://pubmed.ncbi.nlm.nih.gov/27056178 Page: p.442
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 Page: p.536, 537	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: acute myeloid leukaemia Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/25733005 Page: p.536, 537	DLT: Transaminases increased, Multiorgan failure... Dose limiting toxicities: Transaminases increased (50%) Multiorgan failure (grade 5, 25%) Sepsis syndrome (grade 5, 25%) Sources: https://pubmed.ncbi.nlm.nih.gov/25733005 Page: p.536, 537

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 Page: p.442	unhealthy, ADULT n = 2 Health Status: unhealthy Condition: melanoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/27056178 Page: p.442
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 Page: p.442	unhealthy, ADULT n = 2 Health Status: unhealthy Condition: melanoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/27056178 Page: p.442
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 Page: p.442	unhealthy, ADULT n = 11 Health Status: unhealthy Condition: melanoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/27056178 Page: p.442
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 Page: p.442	unhealthy, ADULT n = 11 Health Status: unhealthy Condition: melanoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/27056178 Page: p.442
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 Page: p.442	unhealthy, ADULT n = 11 Health Status: unhealthy Condition: melanoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/27056178 Page: p.442
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 Page: p.442	unhealthy, ADULT n = 11 Health Status: unhealthy Condition: melanoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/27056178 Page: p.442
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 Page: p.537	unhealthy, ADULT n = 3 Health Status: unhealthy Condition: acute myeloid leukaemia Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/25733005 Page: p.537
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 Page: p.537	unhealthy, ADULT n = 3 Health Status: unhealthy Condition: acute myeloid leukaemia Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/25733005 Page: p.537
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 Page: p.442	unhealthy, ADULT n = 11 Health Status: unhealthy Condition: melanoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/27056178 Page: p.442
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 Page: p.442	unhealthy, ADULT n = 11 Health Status: unhealthy Condition: melanoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/27056178 Page: p.442
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 Page: p.442	unhealthy, ADULT n = 11 Health Status: unhealthy Condition: melanoma Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/27056178 Page: p.442
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 Page: p.536, 537	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: acute myeloid leukaemia Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/25733005 Page: p.536, 537
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 Page: p.536, 537	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: acute myeloid leukaemia Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/25733005 Page: p.536, 537
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 Page: p.536, 537	unhealthy, ADULT n = 4 Health Status: unhealthy Condition: acute myeloid leukaemia Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 4 Sources: https://pubmed.ncbi.nlm.nih.gov/25733005 Page: p.536, 537

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461	P-gp 1537 BCRP 561

Drug as perpetrator

Target	Modality	Activity
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363677357	inconclusive [IC50 9.2 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=404904707	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=440681667	yes [IC50 21.3174 uM]
CYP2D6 1891	inhibitor 3277 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 1737	substrate 3367 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 561	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/31972220/	yes
P-gp 1537	substrate 3367 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
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
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=
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
Molcore	MC110895	http://www.molcore.com/CatMC110895.html
Molnova	M16509	https://www.molnova.com/en/serch-list.html?keywords=M16509
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
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
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/

PubMed

Title	Date	PubMed
		252160673
An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer.	2009 Apr 9	19360080
Targeting NEDD8-activated cullin-RING ligases for the treatment of cancer.	2009 Jun 15	19509147
SUMO, Ubiquitin, UBL Proteins: Implications For Human Diseases - Fifth International Conference.	2010 Apr	20373248
Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics.	2010 Dec 10	21145461
NEDD8-targeting drug MLN4924 elicits DNA rereplication by stabilizing Cdt1 in S phase, triggering checkpoint activation, apoptosis, and senescence in cancer cells.	2010 Dec 15	21159650
Substrate-assisted inhibition of ubiquitin-like protein-activating enzymes: the NEDD8 E1 inhibitor MLN4924 forms a NEDD8-AMP mimetic in situ.	2010 Jan 15	20129059
Biochemical and cellular effects of inhibiting Nedd8 conjugation.	2010 Jul 30	20603103
Inhibition of NEDD8-activating enzyme: a novel approach for the treatment of acute myeloid leukemia.	2010 May 6	20203261
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 Sep 2	20525923
Inactivation of SAG E3 ubiquitin ligase blocks embryonic stem cell differentiation and sensitizes leukemia cells to retinoid acid.	2011	22110742
Rictor Undergoes Glycogen Synthase Kinase 3 (GSK3)-dependent, FBXW7-mediated Ubiquitination and Proteasomal Degradation.	2015 May 29	25897075

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

Name

Type

Language

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 [INN]

Common Name

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