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

General Information of Drug (ID: DMD3XMW)

• Drug Name: Cethrin Drug Info
• Synonyms: Quinacrine, Dihydrochloride

Indication

Disease Entry	ICD 11	Status	REF
Spinal cord injury	ND51.2	Phase 1/2	[1]

• Cross-matching ID:
  PubChem CID: 16760629
  TTD Drug ID: DMD3XMW

Molecule-Related Drug Atlas

Drug(s) Targeting Rho-associated protein kinase (ROCK)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Netarsudil	DM0LPI9	Open-angle glaucoma	9C61	Approved	[5]
Ximelegatran	DMU8ANS	Myocardial infarction	BA41-BA43	Approved	[6]
Roclatan	DMVQ5X1	Glaucoma/ocular hypertension	9C61	Phase 3	[7]
AR-12286	DM5TC43	Glaucoma/ocular hypertension	9C61	Phase 2	[8]
AMA-76	DMBWNX5	Glaucoma/ocular hypertension	9C61	Phase 2	[9]
Y-39983	DMXSEHF	Glaucoma/ocular hypertension	9C61	Phase 1/2	[10]
STM 434	DMDF29A	Ovarian cancer	2C73	Phase 1	[11]
AT13148	DMYIPKJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[12]
Hexahydro azepinone derivative 1	DMC1ZIX	N. A.	N. A.	Patented	[11]
Isoquinoline sulfonyl derivative 2	DMT5E7M	N. A.	N. A.	Patented	[11]

Drug(s) Affected By Transforming protein RhoA (RHOA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[13]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[14]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[15]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[16]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[17]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[17]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[18]
Lovastatin	DM9OZWQ	Arteriosclerosis	BD40	Approved	[19]
Pamidronate	DMB4AVP	Bone Paget disease		Approved	[20]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[21]

Drug(s) Affected By Nuclear receptor subfamily 4 group A member 3 (NR4A3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Mercaptopurine	DMTM2IK	Acute lymphoblastic leukaemia	2A85	Approved	[22]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[23]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[24]
Methylprednisolone	DM4BDON	Acute adrenal insufficiency		Approved	[23]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[25]
Leflunomide	DMR8ONJ	Arthritis	FA20	Approved	[26]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[27]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[28]
Azathioprine	DMMZSXQ	Lupus nephritis	4A40.0Y	Approved	[23]
Melphalan	DMOLNHF	Hematologic disease	3C0Z	Approved	[29]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Rho-associated protein kinase (ROCK)	TTMQO60	NOUNIPROTAC	Modulator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Nuclear receptor subfamily 4 group A member 3 (NR4A3)	OTPBE9R1	NR4A3_HUMAN	Gene/Protein Processing	[3]
Transforming protein RhoA (RHOA)	OT6YOJ9N	RHOA_HUMAN	Gene/Protein Processing	[4]

References

• [1] Emerging drugs for spinal cord injury. Expert Opin Emerg Drugs. 2008 Mar;13(1):63-80.
• [2] A phase I/IIa clinical trial of a recombinant Rho protein antagonist in acute spinal cord injury. J Neurotrauma. 2011 May;28(5):787-96.
• [3] Simvastatin inhibits NOR-1 expression induced by hyperlipemia by interfering with CREB activation. Cardiovasc Res. 2005 Aug 1;67(2):333-41. doi: 10.1016/j.cardiores.2005.03.016. Epub 2005 Apr 21.
• [4] Use of synthetic isoprenoids to target protein prenylation and Rho GTPases in breast cancer invasion. PLoS One. 2014 Feb 26;9(2):e89892. doi: 10.1371/journal.pone.0089892. eCollection 2014.
• [5] Effect of 0.04% AR-13324, a ROCK, and norepinephrine transporter inhibitor, on aqueous humor dynamics in normotensive monkey eyes. J Glaucoma. 2015 Jan;24(1):51-4.
• [6] Pharmacological properties of Y-27632, a specific inhibitor of rho-associated kinases. Mol Pharmacol. 2000 May;57(5):976-83.
• [7] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [8] Ocular hypotensive effect of the Rho kinase inhibitor AR-12286 in patients with glaucoma and ocular hypertension. Am J Ophthalmol. 2011 Nov;152(5):834-41.e1.
• [9] AMA0076, a novel, locally acting Rho kinase inhibitor, potently lowers intraocular pressure in New Zealand white rabbits with minimal hyperemia. Invest Ophthalmol Vis Sci. 2014 Feb 18;55(2):1006-16.
• [10] Effects of Y-39983, a selective Rho-associated protein kinase inhibitor, on blood flow in optic nerve head in rabbits and axonal regeneration of retinal ganglion cells in rats.Curr Eye Res. 2011 Oct;36(10):964-70.
• [11] Rho kinase inhibitors: a patent review (2014 - 2016).Expert Opin Ther Pat. 2017 Apr;27(4):507-515.
• [12] Company report (Astex)
• [13] Cannabidiol and Oxygen-Ozone Combination Induce Cytotoxicity in Human Pancreatic Ductal Adenocarcinoma Cell Lines. Cancers (Basel). 2020 Sep 27;12(10):2774. doi: 10.3390/cancers12102774.
• [14] Functional gene expression profile underlying methotrexate-induced senescence in human colon cancer cells. Tumour Biol. 2011 Oct;32(5):965-76.
• [15] Cytoskeletal activation and altered gene expression in endothelial barrier regulation by simvastatin. Am J Respir Cell Mol Biol. 2004 May;30(5):662-70. doi: 10.1165/rcmb.2003-0267OC. Epub 2003 Nov 20.
• [16] Quercetin inhibits migration and invasion of SAS human oral cancer cells through inhibition of NF-B and matrix metalloproteinase-2/-9 signaling pathways. Anticancer Res. 2013 May;33(5):1941-50.
• [17] Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitro. J Invest Dermatol. 2005 Jul;125(1):143-53.
• [18] Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
• [19] Combining prenylation inhibitors causes synergistic cytotoxicity, apoptosis and disruption of RAS-to-MAP kinase signalling in multiple myeloma cells. Br J Haematol. 2005 Sep;130(6):912-25. doi: 10.1111/j.1365-2141.2005.05696.x.
• [20] Pamidronate induced anti-proliferative, apoptotic, and anti-migratory effects in hepatocellular carcinoma. J Hepatol. 2006 Jan;44(1):142-50. doi: 10.1016/j.jhep.2005.09.022. Epub 2005 Nov 9.
• [21] RhoA GTPase inactivation by statins induces osteosarcoma cell apoptosis by inhibiting p42/p44-MAPKs-Bcl-2 signaling independently of BMP-2 and cell differentiation. Cell Death Differ. 2006 Nov;13(11):1845-56. doi: 10.1038/sj.cdd.4401873. Epub 2006 Feb 10.
• [22] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [23] Antirheumatic drug response signatures in human chondrocytes: potential molecular targets to stimulate cartilage regeneration. Arthritis Res Ther. 2009;11(1):R15.
• [24] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [25] Expression profile analysis of human peripheral blood mononuclear cells in response to aspirin. Arch Immunol Ther Exp (Warsz). 2005 Mar-Apr;53(2):151-8.
• [26] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [27] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [28] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [29] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.