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

General Information of Drug (ID: DM0BHL8)

• Drug Name: CLIK-148 Drug Info
• Synonyms: SCHEMBL7207304

Indication

Disease Entry	ICD 11	Status	REF
Rheumatoid arthritis	FA20	Preclinical	[1]

• Cross-matching ID:
  PubChem CID: 9801663
  TTD Drug ID: DM0BHL8

Molecule-Related Drug Atlas

Drug(s) Targeting Cathepsin L (CTSL)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
KGP94	DM2NZ6K	Coagulation defect	3B10.0	Clinical trial	[4]
PMID27998201-Compound-12	DM8QZNC	Bone cancer	2B5Z	Patented	[5]
PMID27998201-Compound-5	DMVZ0ND	Chronic obstructive pulmonary disease	CA22	Patented	[5]
PMID27998201-Compound-9	DM1JOZN	Rheumatoid arthritis	FA20	Patented	[5]
PMID25399719-Compound-17	DMRXKJZ	N. A.	N. A.	Patented	[6]
PMID27998201-Compound-17	DMAZVHJ	Hair loss	ED70	Patented	[5]
Phenylalanine derivative 1	DMVYP8K	Glioma	2A00.0	Patented	[5]
PMID27998201-Compound-7	DMU4QYR	Abdominal aortic aneurysm	BD50.4	Patented	[5]
PMID27998201-Compound-6	DM0LGTY	N. A.	N. A.	Patented	[5]
PMID27998201-Compound-1	DM5QH4C	Coronavirus infection	1D92	Patented	[5]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[7]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[8]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[9]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[10]
Cidofovir	DMA13GD	Cytomegalovirus infection	1D82	Approved	[11]
Paclitaxel	DMLB81S	Breast carcinoma		Approved	[12]
Floxuridine	DM04LR2	Colorectal cancer	2B91.Z	Approved	[13]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[14]
Mechlorethamine	DM0CVXA	Chronic myelogenous leukaemia	2A20.0	Approved	[15]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[16]

Drug(s) Affected By Prohibitin 1 (PHB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[17]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[18]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[19]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[20]
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[21]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[19]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[22]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[23]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[24]
Ethanol	DMDRQZU	Chronic pain	MG30	Approved	[25]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cathepsin L (CTSL)	TT36ETB	CATL1_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]
Prohibitin 1 (PHB1)	OTZNXYS2	PHB1_HUMAN	Gene/Protein Processing	[3]

References

• [1] Lysosomes as a therapeutic target. Nat Rev Drug Discov. 2019 Dec;18(12):923-948.
• [2] Structure-based development of specific inhibitors for individual cathepsins and their medical applications. Proc Jpn Acad Ser B Phys Biol Sci. 2011;87(2):29-39.
• [3] Inhibition of cathepsin L lowers the apoptotic threshold of glioblastoma cells by up-regulating p53 and transcription of caspases 3 and 7. Apoptosis. 2011 Jul;16(7):671-82. doi: 10.1007/s10495-011-0600-6.
• [4] Functionalized benzophenone, thiophene, pyridine, and fluorene thiosemicarbazone derivatives as inhibitors of cathepsin L. Bioorg Med Chem Lett. 2010 Nov 15;20(22):6610-5.
• [5] Cathepsin B and L inhibitors: a patent review (2010 - present).Expert Opin Ther Pat. 2017 Jun;27(6):643-656.
• [6] An updated patent review of calpain inhibitors (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):17-31.
• [7] 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.
• [8] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [9] 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.
• [10] 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.
• [11] Induction of apoptosis by cidofovir in human papillomavirus (HPV)-positive cells. Oncol Res. 2000;12(9-10):397-408. doi: 10.3727/096504001108747855.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [18] Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
• [19] Comparison of the gene expression profiles of monocytic versus granulocytic lineages of HL-60 leukemia cell differentiation by DNA microarray analysis. Life Sci. 2003 Aug 15;73(13):1705-19. doi: 10.1016/s0024-3205(03)00515-0.
• [20] DNA array analysis of the effects of aspirin on colon cancer cells: involvement of Rac1. Carcinogenesis. 2004 Jul;25(7):1293-8.
• [21] Genomic and proteomic analysis of the effects of cannabinoids on normal human astrocytes. Brain Res. 2008 Jan 29;1191:1-11.
• [22] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [23] Integrated 'omics analysis reveals new drug-induced mitochondrial perturbations in human hepatocytes. Toxicol Lett. 2018 Jun 1;289:1-13.
• [24] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [25] Effects of acute ethanol treatment on NCCIT cells and NCCIT cell-derived embryoid bodies (EBs). Toxicol In Vitro. 2010 Sep;24(6):1696-704. doi: 10.1016/j.tiv.2010.05.017. Epub 2010 May 26.