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

General Information of Drug (ID: DMXB95R)

• Drug Name: IC261 Drug Info
• Synonyms: IC-261; IC 261

Indication

Disease Entry	ICD 11	Status	REF
Pancreatic cancer	2C10	Preclinical	[1]

• Cross-matching ID:
  PubChem CID: 5288600
  TTD Drug ID: DMXB95R

Molecule-Related Drug Atlas

Drug(s) Targeting Casein kinase I alpha (CSNK1A1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BTX-A51	DMC8XHQ	Advanced solid tumour	2A00-2F9Z	Phase 1	[4]
US9096594, 3	DM8UOKE	N. A.	N. A.	Patented	[5]
D-4476	DMHD3R8	Chronic lymphocytic leukaemia	2A82.0	Preclinical	[6]
PMID24900428C14	DMU4BL2	Discovery agent	N.A.	Investigative	[7]

Drug(s) Targeting Casein kinase I delta (CSNK1D)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
D-4476	DMHD3R8	Chronic lymphocytic leukaemia	2A82.0	Preclinical	[8]
PF-4800567	DM8P9ST	Chronic lymphocytic leukaemia	2A82.0	Preclinical	[9]
PF-670462	DMTJBP9	Chronic lymphocytic leukaemia	2A82.0	Preclinical	[10]
PMID24900428C14	DMU4BL2	Discovery agent	N.A.	Investigative	[7]

Drug(s) Targeting Casein kinase I epsilon (CSNK1E)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Umbralisib	DMYRBO1	Follicular lymphoma	2A80	Approved	[11]
PF-4800567	DM8P9ST	Chronic lymphocytic leukaemia	2A82.0	Preclinical	[9]
PF-670462	DMTJBP9	Chronic lymphocytic leukaemia	2A82.0	Preclinical	[10]

Drug(s) Affected By Cellular tumor antigen p53 (TP53)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[12]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[13]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[14]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[15]
Cidofovir	DMA13GD	Cytomegalovirus infection	1D82	Approved	[16]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[17]
Floxuridine	DM04LR2	Colorectal cancer	2B91.Z	Approved	[18]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[19]
Mechlorethamine	DM0CVXA	Chronic myelogenous leukaemia	2A20.0	Approved	[20]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[21]

Drug(s) Affected By E3 ubiquitin-protein ligase Mdm2 (MDM2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[22]
Flucytosine	DM13VTW	Cryptococcal meningitis		Approved	[23]
Ganciclovir	DM1MBYQ	Cytomegalovirus infection	1D82	Approved	[23]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[24]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[25]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[26]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[27]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[14]
Acetic Acid, Glacial	DM4SJ5Y	infection in the ear canal	AA0Y	Approved	[28]
Amifostine	DM5FL14	Mucositis	CA00	Approved	[29]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Casein kinase I alpha (CSNK1A1)	TTFQEMX	KC1A_HUMAN	Inhibitor	[2]
Casein kinase I delta (CSNK1D)	TTH30UI	KC1D_HUMAN	Inhibitor	[2]
Casein kinase I epsilon (CSNK1E)	TTA8PLI	KC1E_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Gene/Protein Processing	[3]
E3 ubiquitin-protein ligase Mdm2 (MDM2)	OTOVXARF	MDM2_HUMAN	Gene/Protein Processing	[3]

References

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• [2] Crystal structure of a conformation-selective casein kinase-1 inhibitor. J Biol Chem. 2000 Jun 30;275(26):20052-60.
• [3] Inhibition of casein kinase I delta alters mitotic spindle formation and induces apoptosis in trophoblast cells. Oncogene. 2005 Dec 1;24(54):7964-75. doi: 10.1038/sj.onc.1208941.
• [4] Clinical pipeline report, company report or official report of BioTheryX.
• [5] Kinase inhibitors and methods of use thereof. US9096594.
• [6] Discovery of N6-phenyl-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamine derivatives as novel CK1 inhibitors using common-feature pharmacophore model based virtual screening and hit-to-lead optimization. Eur J Med Chem. 2012 Oct;56:30-8.
• [7] Structure-Based Design of Potent and Selective CK1gamma Inhibitors. ACS Med Chem Lett. 2012 Oct 18;3(12):1059-64.
• [8] The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
• [9] Selective inhibition of casein kinase 1 epsilon minimally alters circadian clock period. J Pharmacol Exp Ther. 2009 Aug;330(2):430-9.
• [10] Casein kinase 1 is a therapeutic target in chronic lymphocytic leukemia. Blood. 2018 Mar 15;131(11):1206-1218.
• [11] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
• [12] p53-R175H mutant gains new function in regulation of doxorubicin-induced apoptosis. Int J Cancer. 2005 Apr 10;114(3):331-6. doi: 10.1002/ijc.20818.
• [13] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [14] Azidothymidine and cisplatin increase p14ARF expression in OVCAR-3 ovarian cancer cell line. Toxicol Appl Pharmacol. 2006 Oct 1;216(1):89-97. doi: 10.1016/j.taap.2006.04.015. Epub 2006 May 19.
• [15] Quantitative analysis of gene expression changes in response to genotoxic compounds. Toxicol In Vitro. 2017 Mar;39:15-28. doi: 10.1016/j.tiv.2016.11.004. Epub 2016 Nov 5.
• [16] Induction of apoptosis by cidofovir in human papillomavirus (HPV)-positive cells. Oncol Res. 2000;12(9-10):397-408. doi: 10.3727/096504001108747855.
• [17] Gallic acid potentiates the apoptotic effect of paclitaxel and carboplatin via overexpression of Bax and P53 on the MCF-7 human breast cancer cell line. J Biochem Mol Toxicol. 2021 Feb;35(2):e22638. doi: 10.1002/jbt.22638. Epub 2020 Oct 1.
• [18] Regulation of human dUTPase gene expression and p53-mediated transcriptional repression in response to oxaliplatin-induced DNA damage. Nucleic Acids Res. 2009 Jan;37(1):78-95. doi: 10.1093/nar/gkn910. Epub 2008 Nov 16.
• [19] Role of miRNA in the regulation of cannabidiol-mediated apoptosis in neuroblastoma cells. Oncotarget. 2019 Jan 1;10(1):45-59. doi: 10.18632/oncotarget.26534. eCollection 2019 Jan 1.
• [20] Nitrogen Mustard Alkylates and Cross-Links p53 in Human Keratinocytes. Chem Res Toxicol. 2022 Apr 18;35(4):636-650. doi: 10.1021/acs.chemrestox.1c00420. Epub 2022 Mar 21.
• [21] Fulvestrant induces resistance by modulating GPER and CDK6 expression: implication of methyltransferases, deacetylases and the hSWI/SNF chromatin remodelling complex. Br J Cancer. 2013 Nov 12;109(10):2751-62. doi: 10.1038/bjc.2013.583. Epub 2013 Oct 29.
• [22] Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
• [23] Mechanisms of thymidine kinase/ganciclovir and cytosine deaminase/ 5-fluorocytosine suicide gene therapy-induced cell death in glioma cells. Oncogene. 2005 Feb 10;24(7):1231-43. doi: 10.1038/sj.onc.1208290.
• [24] In vitro antioxidant and antigenotoxic potentials of 3,5-O-di-galloylquinic acid extracted from Myrtus communis leaves and modulation of cell gene expression by H2O2. J Appl Toxicol. 2012 May;32(5):333-41.
• [25] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [26] HMG-CoA reductase inhibitors, statins, induce phosphorylation of Mdm2 and attenuate the p53 response to DNA damage. FASEB J. 2005 Mar;19(3):476-8. doi: 10.1096/fj.04-2745fje. Epub 2004 Dec 29.
• [27] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [28] Motexafin gadolinium and zinc induce oxidative stress responses and apoptosis in B-cell lymphoma lines. Cancer Res. 2005 Dec 15;65(24):11676-88.
• [29] Amifostine impairs p53-mediated apoptosis of human myeloid leukemia cells. Mol Cancer Ther. 2003 Sep;2(9):893-900.