Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMUNJZB)

• Drug Name: UCN-01 Drug Info
• 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
• Cross-matching ID:
  PubChem CID: 72271
  CAS Number: CAS 112953-11-4
  TTD Drug ID: DMUNJZB
  VARIDT Drug ID: DR01437

Molecule-Related Drug Atlas

Drug(s) Transported By Breast cancer resistance protein (ABCG2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Solid tumour/cancer	2A00-2F9Z	Approved	[8]
Methotrexate	DM2TEOL	leukaemia	2A60-2B33	Approved	[9]
Folic acid	DMEMBJC	Folate-deficiency anemia	3A02.Y	Approved	[10]
Fluorouracil	DMUM7HZ	Solid tumour/cancer	2A00-2F9Z	Approved	[11]
Cisplatin	DMRHGI9	Solid tumour/cancer	2A00-2F9Z	Approved	[12]
Progesterone	DMUY35B	Premature labour	JB00	Approved	[13]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[14]
Estradiol	DMUNTE3	Breast cancer	2C60-2C65	Approved	[13]
Sulfasalazine	DMICA9H	Irritable bowel syndrome	DD91.0	Approved	[15]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[16]

Drug(s) Targeting Checkpoint kinase-1 (CHK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LY2603618	DMCXRZF	Pancreatic cancer	2C10	Phase 2	[17]
SCH-900776	DM67EMK	Solid tumour/cancer	2A00-2F9Z	Phase 2	[18]
LY2606368	DM4XMF7	Ovarian cancer	2C73	Phase 2	[19]
LY2880070	DMADEHZ	Solid tumour/cancer	2A00-2F9Z	Phase 1/2	[20]
RG7741	DMK6P9J	Lymphoma	2A80-2A86	Phase 1	[21]
GDC-0425	DMDZ26X	Lymphoma	2A80-2A86	Phase 1	[22]
AZD7762	DM1FW0C	Solid tumour/cancer	2A00-2F9Z	Phase 1	[23]
MK-8776	DMAS1RB	Hodgkin lymphoma	2B30	Phase 1	[24]
Diamidothiazole derivative 1	DM02V5Q	N. A.	N. A.	Patented	[25]
XL844	DMHTG38	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[26]

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]

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.