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
Topological Polar Surface Area (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

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], [3], [4], [5], [6]

Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [7]
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 CHK1 inhibition as a strategy for targeting Fanconi Anemia (FA) DNA repair pathway deficient tumors. Mol Cancer. 2009 Apr 16;8:24.
4 UCN-01 inhibits p53 up-regulation and abrogates gamma-radiation-induced G(2)-M checkpoint independently of p53 by targeting both of the checkpoint kinases, Chk2 and Chk1. Cancer Res. 2002 Oct 15;62(20):5743-8.
5 The PI3K/Akt pathway as a target in the treatment of hematologic malignancies. Anticancer Agents Med Chem. 2009 Jun;9(5):550-9.
6 Cyclin-dependent kinase inhibitors as potential targeted anticancer agents. Invest New Drugs. 2009 Dec;27(6):586-94.
7 Pharmacogenomic importance of ABCG2. Pharmacogenomics. 2008 Aug;9(8):1005-9.
8 Doxorubicin transport by RALBP1 and ABCG2 in lung and breast cancer. Int J Oncol. 2007 Mar;30(3):717-25.
9 Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer Res. 2003 Sep 1;63(17):5538-43.
10 The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models. Mol Pharmacol. 2007 Jan;71(1):240-9.
11 Role of BCRP as a biomarker for predicting resistance to 5-fluorouracil in breast cancer. Cancer Chemother Pharmacol. 2009 May;63(6):1103-10.
12 Inhibiting the function of ABCB1 and ABCG2 by the EGFR tyrosine kinase inhibitor AG1478. Biochem Pharmacol. 2009 Mar 1;77(5):781-93.
13 Sterol transport by the human breast cancer resistance protein (ABCG2) expressed in Lactococcus lactis. J Biol Chem. 2003 Jun 6;278(23):20645-51.
14 The phytoestrogen genistein enhances multidrug resistance in breast cancer cell lines by translational regulation of ABC transporters. Cancer Lett. 2016 Jun 28;376(1):165-72.
15 Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice. Pharm Res. 2009 Feb;26(2):480-7.
16 Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood. 2004 Nov 1;104(9):2940-2.
17 Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor. Invest New Drugs. 2014 Apr;32(2):213-26.
18 Targeting the replication checkpoint using SCH 900776, a potent and functionally selective CHK1 inhibitor identified via high content screening. Mol Cancer Ther. 2011 Apr;10(4):591-602.
19 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
20 A phase Ib study of oral Chk1 inhibitor LY2880070 in combination with gemcitabine in patients with advanced or metastatic cancer. Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 3581-3581.
21 National Cancer Institute Drug Dictionary (drug id 730054).
22 Quantitative assessment of BCL-2:BIM complexes as a pharmacodynamic marker for venetoclax (ABT-199).
23 Clinical pipeline report, company report or official report of AstraZeneca (2009).
24 Chk1 Inhibitor MK-8776 Restores the Sensitivity of Chemotherapeutics in P-glycoprotein Overexpressing Cancer Cells. Int J Mol Sci. 2019 Aug 22;20(17):4095.
25 Cyclin-dependent kinase inhibitors for cancer therapy: a patent review (2009 - 2014).Expert Opin Ther Pat. 2015;25(9):953-70.
26 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.