Details of the Drug

General Information of Drug (ID: DMUNJZB)

Drug Name
UCN-01
Synonyms
UCN; UCN01; Ucn 01; KRX-0601; KW-2401; UCN-02; (5s,6r,7r,9r,16r)-16-hydroxy-6-methoxy-5-methyl-7-(methylamino)-6,7,8,9,15,16-hexahydro-5h,14h-5,9-epoxy-4b,9a,15-triazadibenzo[b,h]cyclonona[1,2,3,4-jkl]cyclopenta[e]-as-indacen-14-one; 7-Hydroxystaurosporine; 7-hydroxystaurosporine (UCN-01)
Indication
Disease Entry ICD 11 Status REF
Non-small-cell lung cancer 2C25.Y Phase 2 [1]
Therapeutic Class
Anticancer Agents
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 482.5
Logarithm of the Partition Coefficient (xlogp) 2.7
Rotatable Bond Count (rotbonds) 2
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 5
Chemical Identifiers
Formula
C28H26N4O4
IUPAC Name
(2S,3R,4R,6R,18R)-18-hydroxy-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one
Canonical SMILES
C[C@@]12[C@@H]([C@@H](C[C@@H](O1)N3C4=CC=CC=C4C5=C6C(=C7C8=CC=CC=C8N2C7=C53)[C@H](NC6=O)O)NC)OC
InChI
InChI=1S/C28H26N4O4/c1-28-25(35-3)15(29-2)12-18(36-28)31-16-10-6-4-8-13(16)19-21-22(27(34)30-26(21)33)20-14-9-5-7-11-17(14)32(28)24(20)23(19)31/h4-11,15,18,25,27,29,34H,12H2,1-3H3,(H,30,33)/t15-,18-,25-,27-,28+/m1/s1
InChIKey
PBCZSGKMGDDXIJ-HQCWYSJUSA-N
Cross-matching ID
PubChem CID
72271
CAS Number
112953-11-4
DrugBank ID
DB01933
TTD ID
D0Z9VY
VARIDT ID
DR01437
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Checkpoint kinase-1 (CHK1) TTTU902 CHK1_HUMAN Inhibitor [2]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [3]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
3-phosphoinositide-dependent protein kinase 1 (PDPK1) OTT09ZVP PDPK1_HUMAN Gene/Protein Processing [4]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Gene/Protein Processing [5]
Baculoviral IAP repeat-containing protein 5 (BIRC5) OTILXZYL BIRC5_HUMAN Drug Response [6]
BAG family molecular chaperone regulator 1 (BAG1) OTRQNIA4 BAG1_HUMAN Gene/Protein Processing [5]
Cellular tumor antigen p53 (TP53) OTIE1VH3 P53_HUMAN Gene/Protein Processing [7]
E3 ubiquitin-protein ligase XIAP OT24GP9B XIAP_HUMAN Gene/Protein Processing [5]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) OT2YYI1A MCL1_HUMAN Gene/Protein Processing [5]
Poly polymerase 1 (PARP1) OT310QSG PARP1_HUMAN Drug Response [8]
Protein kinase C alpha type (PRKCA) OT5UWNRD KPCA_HUMAN Gene/Protein Processing [4]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Gene/Protein Processing [9]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Non-small-cell lung cancer
ICD Disease Classification 2C25.Y
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Checkpoint kinase-1 (CHK1) DTT CHEK1 7.22E-191 1.43 4.74
Breast cancer resistance protein (ABCG2) DTP BCRP 3.87E-47 -1.28E+00 -1.63E+00
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 ClinicalTrials.gov (NCT00082017) UCN-01 (7-Hydroxystaurosporine) to Treat Relapsed T-Cell Lymphomas. U.S. National Institutes of Health.
2 Characterization of an inhibitory dynamic pharmacophore for the ERCC1-XPA interaction using a combined molecular dynamics and virtual screening app... J Mol Graph Model. 2009 Sep;28(2):113-30.
3 Pharmacogenomic importance of ABCG2. Pharmacogenomics. 2008 Aug;9(8):1005-9.
4 Specificity and mechanism of action of some commonly used protein kinase inhibitors. Biochem J. 2000 Oct 1;351(Pt 1):95-105.
5 Protein kinase inhibitors flavopiridol and 7-hydroxy-staurosporine down-regulate antiapoptosis proteins in B-cell chronic lymphocytic leukemia. Blood. 2000 Jul 15;96(2):393-7.
6 A study of cytotoxic synergy of UCN-01 and flavopiridol in syngeneic pair of cell lines. Invest New Drugs. 2005 Aug;23(4):299-309. doi: 10.1007/s10637-005-1438-y.
7 UCN-01 induces cytotoxicity toward human CLL cells through a p53-independent mechanism. Exp Hematol. 2001 Jun;29(6):703-8. doi: 10.1016/s0301-472x(01)00649-x.
8 The PARP inhibitor PJ34 causes a PARP1-independent, p21 dependent mitotic arrest. DNA Repair (Amst). 2011 Oct 10;10(10):1003-13. doi: 10.1016/j.dnarep.2011.07.006. Epub 2011 Aug 12.
9 The expression of retinoblastoma and Sp1 is increased by low concentrations of cyclin-dependent kinase inhibitors. Eur J Biochem. 2003 Dec;270(24):4809-22. doi: 10.1046/j.1432-1033.2003.03874.x.