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
CHEBI:95028
CAS Number
905579-51-3
DrugBank ID
DB11759
TTD ID
D0ZD2M
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

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
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Gene/Protein Processing [6]
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 17 (CCL17) OTIKW21L CCL17_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]
C-X-C chemokine receptor type 3 (CXCR3) OTIGS220 CXCR3_HUMAN Gene/Protein Processing [6]
C-X-C chemokine receptor type 5 (CXCR5) OTVBCQZX CXCR5_HUMAN Gene/Protein Processing [6]
C-X-C motif chemokine 9 (CXCL9) OTMFVZKZ CXCL9_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.