Details of the Drug

General Information of Drug (ID: DMLN4V5)

Drug Name
EPZ-004777
Synonyms DOT1L inhibitors (mixed lineage leukemia); DOT1L inhibitors (leukemia), Epizyme/GSK; DOT1L inhibitors (mixed lineage leukemia), Epizyme/GlaxoSmithKline
Indication
Disease Entry ICD 11 Status REF
leukaemia 2A60-2B33 Investigative [1]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 1 Molecular Weight (mw) 539.7
Logarithm of the Partition Coefficient (xlogp) 2.4
Rotatable Bond Count (rotbonds) 10
Hydrogen Bond Donor Count (hbonddonor) 5
Hydrogen Bond Acceptor Count (hbondacc) 8
Chemical Identifiers
Formula
C28H41N7O4
IUPAC Name
1-[3-[[(2R,3S,4R,5R)-5-(4-aminopyrrolo[2,3-d]pyrimidin-7-yl)-3,4-dihydroxyoxolan-2-yl]methyl-propan-2-ylamino]propyl]-3-(4-tert-butylphenyl)urea
Canonical SMILES
CC(C)N(CCCNC(=O)NC1=CC=C(C=C1)C(C)(C)C)C[C@@H]2[C@H]([C@H]([C@@H](O2)N3C=CC4=C(N=CN=C43)N)O)O
InChI
InChI=1S/C28H41N7O4/c1-17(2)34(13-6-12-30-27(38)33-19-9-7-18(8-10-19)28(3,4)5)15-21-22(36)23(37)26(39-21)35-14-11-20-24(29)31-16-32-25(20)35/h7-11,14,16-17,21-23,26,36-37H,6,12-13,15H2,1-5H3,(H2,29,31,32)(H2,30,33,38)/t21-,22-,23-,26-/m1/s1
InChIKey
WXRGFPHDRFQODR-ICLZECGLSA-N
Cross-matching ID
PubChem CID
56962336
ChEBI ID
CHEMBL2169919
CAS Number
1338466-77-5
TTD ID
D09ENZ
Drug-Molecule Activity Atlas (DMA)NEW Click to Jump to the Detailed DMA Information of This Drug
Drug Pharmacogenomic Perturbation (DPP)NEW Click to Jump to the Detailed DPP Information of This Drug
Drug ADMET Endpoint Profile (DAE)NEW Click to Jump to the Detailed DAE Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Histone-lysine N-methyltransferase (HLNM) TTSZ8T1 DOT1L_HUMAN Inhibitor [2]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
E3 ubiquitin-protein ligase MYCBP2 (MYCBP2) OTHODA1F MYCB2_HUMAN Gene/Protein Processing [3]
Fatty acid CoA ligase Acsl3 (ACSL3) OT3MWER1 ACSL3_HUMAN Gene/Protein Processing [3]
Homeobox protein Hox-A9 (HOXA9) OTKNK5H0 HXA9_HUMAN Gene/Protein Processing [4]
Homeobox protein Hox-B3 (HOXB3) OT9UC5PE HXB3_HUMAN Gene/Protein Processing [4]
Homeobox protein Hox-B8 (HOXB8) OTKHOD17 HXB8_HUMAN Gene/Protein Processing [4]
Homeobox protein Meis1 (MEIS1) OTH9DKAD MEIS1_HUMAN Gene/Protein Processing [4]
Kallikrein-2 (KLK2) OT9RE37R KLK2_HUMAN Gene/Protein Processing [3]
Myc proto-oncogene protein (MYC) OTPV5LUK MYC_HUMAN Gene/Protein Processing [3]
Probable E3 ubiquitin-protein ligase HERC3 (HERC3) OTWMKYD9 HERC3_HUMAN Gene/Protein Processing [3]
RNA polymerase II elongation factor ELL2 (ELL2) OTZJRTFM ELL2_HUMAN Gene/Protein Processing [3]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease leukaemia
ICD Disease Classification 2A60-2B33
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Histone-lysine N-methyltransferase (HLNM) DTT DOT1L 7.62E-02 0.08 0.2
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7377).
2 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7377).
3 Histone methyltransferase DOT1L coordinates AR and MYC stability in prostate cancer. Nat Commun. 2020 Aug 19;11(1):4153. doi: 10.1038/s41467-020-18013-7.
4 DOT1L as a therapeutic target for the treatment of DNMT3A-mutant acute myeloid leukemia. Blood. 2016 Aug 18;128(7):971-81. doi: 10.1182/blood-2015-11-684225. Epub 2016 Jun 22.