Details of the Drug

General Information of Drug (ID: DMP36KD)

Drug Name
MLN4924
Synonyms
Pevonedistat; 905579-51-3; MLN4924; MLN-4924; MLN 4924; UNII-S3AZD8D215; S3AZD8D215; 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; ((1S,2S,4R)-4-(4-(((S)-2,3-dihydro-1H-inden-1-yl)amino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-hydroxycyclopentyl)methyl sulfamate; C21H25N5O4S; [(1s,2s,4r)-4-{4-[(1s)-2,3-Dihydro-1h-Inden-1-Ylamino]-7h-Pyrrolo[2,3-D]pyrimidin-7-Yl}-2-Hydroxycyclopentyl]methyl Sulfamate; Pevonedistat [USAN:INN]; 3gzn
Indication
Disease Entry ICD 11 Status REF
Myelodysplastic syndrome 2A37 Phase 3 [1]
Acute myelogenous leukaemia 2A41 Phase 2 [2]
Advanced malignancy 2A00-2F9Z Phase 1 [3]
Nasopharyngeal carcinoma 2B6B Investigative [4]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 443.5
Logarithm of the Partition Coefficient (xlogp) 1.7
Rotatable Bond Count (rotbonds) 6
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 8
Chemical Identifiers
Formula
C21H25N5O4S
IUPAC Name
[(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]pyrrolo[2,3-d]pyrimidin-7-yl]-2-hydroxycyclopentyl]methyl sulfamate
Canonical SMILES
C1CC2=CC=CC=C2[C@H]1NC3=C4C=CN(C4=NC=N3)[C@@H]5C[C@H]([C@H](C5)O)COS(=O)(=O)N
InChI
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
InChIKey
MPUQHZXIXSTTDU-QXGSTGNESA-N
Cross-matching ID
PubChem CID
16720766
ChEBI ID
CHEMBL1231160
CAS Number
905579-51-3
UNII
S3AZD8D215
DrugBank ID
DB11759
TTD ID
D0ZD2M
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
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Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
NEDD8-activating enzyme (NAE) TTVKOPM ULA1_HUMAN ; UBA3_HUMAN Modulator [5]
Ubiquitin-like protein Nedd8 (NEDD8) TTNDC4K NEDD8_HUMAN Inhibitor [4]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Bcl-2-binding component 3, isoforms 3/4 (BBC3) OTUAXDAY BBC3B_HUMAN Gene/Protein Processing [6]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Gene/Protein Processing [6]
Bcl-2-like protein 11 (BCL2L11) OTNQQWFJ B2L11_HUMAN Gene/Protein Processing [6]
C-C motif chemokine 22 (CCL22) OTT3QJC2 CCL22_HUMAN Gene/Protein Processing [6]
C-C motif chemokine 5 (CCL5) OTSCA5CK CCL5_HUMAN Gene/Protein Processing [6]
CASP8 and FADD-like apoptosis regulator (CFLAR) OTX14BAS CFLAR_HUMAN Gene/Protein Processing [6]
G1/S-specific cyclin-D2 (CCND2) OTDULQF9 CCND2_HUMAN Gene/Protein Processing [6]
Growth arrest and DNA damage-inducible protein GADD45 beta (GADD45B) OTL9I7LO GA45B_HUMAN Gene/Protein Processing [6]
Heat shock factor protein 1 (HSF1) OTYNJ4KP HSF1_HUMAN Gene/Protein Processing [7]
HLA class II histocompatibility antigen gamma chain (CD74) OTO16X4Q HG2A_HUMAN Gene/Protein Processing [6]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3 Drug discovery: Fresh target for cancer therapy. Nature. 2009 Apr 9;458(7239):709-10.
4 Promoting tumorigenesis in nasopharyngeal carcinoma, NEDD8 serves as a potential theranostic target.Cell Death Dis. 2017 Jun 1;8(6):e2834.
5 Targeting Cullin-RING ligases by MLN4924 induces autophagy via modulating the HIF1-REDD1-TSC1-mTORC1-DEPTOR axis.Cell Death Dis.2012 Sep 6;3:e386.
6 The Nedd8-activating enzyme inhibitor MLN4924 thwarts microenvironment-driven NF-B activation and induces apoptosis in chronic lymphocytic leukemia B cells. Clin Cancer Res. 2014 Mar 15;20(6):1576-89. doi: 10.1158/1078-0432.CCR-13-0987.
7 A Gene Expression Biomarker Predicts Heat Shock Factor 1 Activation in a Gene Expression Compendium. Chem Res Toxicol. 2021 Jul 19;34(7):1721-1737. doi: 10.1021/acs.chemrestox.0c00510. Epub 2021 Jun 25.