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
CHEBI:124920
CAS Number
1338466-77-5
TTD ID
D09ENZ

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
Androgen receptor (AR) OTUBKAZZ ANDR_HUMAN Gene/Protein Processing [3]
Cyclin-A2 (CCNA2) OTPHHYZJ CCNA2_HUMAN Gene/Protein Processing [4]
Cyclin-dependent kinase 2 (CDK2) OTB5DYYZ CDK2_HUMAN Gene/Protein Processing [4]
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 [5]
Homeobox protein Hox-B3 (HOXB3) OT9UC5PE HXB3_HUMAN Gene/Protein Processing [5]
Homeobox protein Hox-B8 (HOXB8) OTKHOD17 HXB8_HUMAN Gene/Protein Processing [5]
Homeobox protein Meis1 (MEIS1) OTH9DKAD MEIS1_HUMAN Gene/Protein Processing [5]
Kallikrein-2 (KLK2) OT9RE37R KLK2_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 Silencing or inhibition of H3K79 methyltransferase DOT1L induces cell cycle arrest by epigenetically modulating c-Myc expression in colorectal cancer. Clin Epigenetics. 2019 Dec 30;11(1):199. doi: 10.1186/s13148-019-0778-y.
5 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.