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

General Information of Drug (ID: DMYK31O)

• Drug Name: MDL-28170 Drug Info
• Synonyms: MDL-2170

Indication

Disease Entry	ICD 11	Status	REF
Alzheimer disease	8A20	Terminated	[1]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[2]

• Cross-matching ID:
  PubChem CID: 72430
  ChEBI ID: CHEBI:82818
  CAS Number: CAS 88191-84-8
  TTD Drug ID: DMYK31O
  VARIDT Drug ID: DR00841

Molecule-Related Drug Atlas

Drug(s) Targeting Calpain-2 (CAPN2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ABT-957	DMB9N4J	Alzheimer disease	8A20	Phase 1	[6]
PMID25399719-Compound-17	DMRXKJZ	N. A.	N. A.	Patented	[7]
Epoxysuccinate derivative 9	DM49FU0	N. A.	N. A.	Patented	[7]
Epoxysuccinate derivative 4	DMCF6M8	N. A.	N. A.	Patented	[7]
Carboxamide derivative 7	DM8TQS4	N. A.	N. A.	Patented	[7]
Epoxysuccinate derivative 7	DMTSPVF	N. A.	N. A.	Patented	[7]
Carboxamide derivative 10	DM5WMO9	N. A.	N. A.	Patented	[7]
Carboxamide derivative 11	DM1DN94	N. A.	N. A.	Patented	[7]
Carboxamide derivative 8	DM6HI34	N. A.	N. A.	Patented	[7]
Epoxysuccinate derivative 10	DMYF39U	N. A.	N. A.	Patented	[7]

Drug(s) Affected By Interleukin-1 alpha (IL1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[8]
Primidone	DM0WX6I	Epilepsy	8A60-8A68	Approved	[9]
Fexofenadine	DM17ONX	Allergic rhinitis	CA08.0	Approved	[9]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[10]
Clavulanate	DM2FGRT	Bacteremia	1A73	Approved	[9]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[11]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[12]
Rofecoxib	DM3P5DA	Osteoarthritis	FA00-FA05	Approved	[9]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[13]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[14]

Drug(s) Affected By Calpain-1 catalytic subunit (CAPN1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[15]
Selenium	DM25CGV	N. A.	N. A.	Approved	[16]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[17]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[18]
Glimepiride	DM5FSJA	Diabetic complication	5A2Y	Approved	[19]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[20]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[21]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[22]
Cantharidin	DMBP5N3	Molluscum contagiosum infection	1E76	Approved	[23]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[24]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Calpain-2 (CAPN2)	TTG5QB7	CAN2_HUMAN	Inhibitor	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Calpain-1 catalytic subunit (CAPN1)	OTK6OQZR	CAN1_HUMAN	Gene/Protein Processing	[4]
Interleukin-1 alpha (IL1A)	OTPSGILV	IL1A_HUMAN	Protein Interaction/Cellular Processes	[5]

References

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• [2] A Large-scale Drug Repositioning Survey for SARS-CoV-2 Antivirals. April 17, 2020.
• [3] Synthesis of a small library of diketopiperazines as potential inhibitors of calpain. Bioorg Med Chem Lett. 2005 Jun 15;15(12):3034-8.
• [4] Calpain is involved in cisplatin-induced endothelial injury in an in vitro three-dimensional blood vessel model. Int J Oncol. 2010 Nov;37(5):1289-96. doi: 10.3892/ijo_00000780.
• [5] Redox-control of the alarmin, Interleukin-1. Redox Biol. 2013 Apr 17;1(1):218-25. doi: 10.1016/j.redox.2013.03.001. eCollection 2013.
• [6] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [7] An updated patent review of calpain inhibitors (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):17-31.
• [8] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [9] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [10] Oxidative Stress Alters miRNA and Gene Expression Profiles in Villous First Trimester Trophoblasts. Biomed Res Int. 2015;2015:257090. doi: 10.1155/2015/257090. Epub 2015 Aug 3.
• [11] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [12] Quercetin potentiates apoptosis by inhibiting nuclear factor-kappaB signaling in H460 lung cancer cells. Biol Pharm Bull. 2013;36(6):944-51. doi: 10.1248/bpb.b12-01004.
• [13] Increased sensitivity for troglitazone-induced cytotoxicity using a human in vitro co-culture model. Toxicol In Vitro. 2009 Oct;23(7):1387-95.
• [14] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [15] Cannabidiol Modulates the Expression of Alzheimer's Disease-Related Genes in Mesenchymal Stem Cells. Int J Mol Sci. 2016 Dec 23;18(1):26. doi: 10.3390/ijms18010026.
• [16] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [17] [Simvastatin-induced apoptosis of K562 cells is mediated by endoplasmic reticulum stress]. Yao Xue Xue Bao. 2008 Apr;43(4):371-7.
• [18] Quercetin induced cell apoptosis and altered gene expression in AGS human gastric cancer cells. Environ Toxicol. 2018 Nov;33(11):1168-1181. doi: 10.1002/tox.22623. Epub 2018 Aug 27.
• [19] A potential role of calpains in sulfonylureas (SUs) -mediated death of human pancreatic cancer cells (1.2B4). Toxicol In Vitro. 2021 Jun;73:105128. doi: 10.1016/j.tiv.2021.105128. Epub 2021 Feb 27.
• [20] Endoplasmic reticulum stress contributes to arsenic trioxide-induced intrinsic apoptosis in human umbilical and bone marrow mesenchymal stem cells. Environ Toxicol. 2016 Mar;31(3):314-28.
• [21] Aspirin Has Antitumor Effects via Expression of Calpain Gene in Cervical Cancer Cells. J Oncol. 2008;2008:285374. doi: 10.1155/2008/285374. Epub 2008 Sep 29.
• [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] Anticancer effects of cantharidin in A431 human skin cancer (Epidermoid carcinoma) cells in vitro and in vivo. Environ Toxicol. 2017 Mar;32(3):723-738. doi: 10.1002/tox.22273. Epub 2016 Apr 25.
• [24] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.