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

General Information of Drug (ID: DMVQ5X1)

• Drug Name: Roclatan Drug Info
• Synonyms: PG324

Indication

Disease Entry	ICD 11	Status	REF
Glaucoma/ocular hypertension	9C61	Phase 3	[1]

• Cross-matching ID:
  PubChem CID: 118984471
  TTD Drug ID: DMVQ5X1
  VARIDT Drug ID: DR01144

Molecule-Related Drug Atlas

Drug(s) Targeting Norepinephrine transporter (NET)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[3]
Amitriptyline	DMK7F9S	Depression	6A70-6A7Z	Approved	[4]
Imipramine	DM2NUH3	Depression	6A70-6A7Z	Approved	[5]
Desipramine	DMT2FDC	Attention deficit hyperactivity disorder	6A05.Z	Approved	[3]
Cocaine	DMSOX7I	Anaesthesia	9A78.6	Approved	[6]
Bupropion	DM5PCS7	Depression	6A70-6A7Z	Approved	[7]
Tapentadol hydrochloride	DMXLSH3	Acute pain	MG31	Approved	[8]
Venlafaxine	DMR6QH0	Anxiety disorder	6B00-6B0Z	Approved	[7]
Trimipramine	DM1SC8M	Major depressive disorder	6A70.3	Approved	[9]
Duloxetine	DM9BI7M	Depression	6A70-6A7Z	Approved	[10]

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	[11]
Ximelegatran	DMU8ANS	Myocardial infarction	BA41-BA43	Approved	[12]
AR-12286	DM5TC43	Glaucoma/ocular hypertension	9C61	Phase 2	[13]
AMA-76	DMBWNX5	Glaucoma/ocular hypertension	9C61	Phase 2	[14]
Cethrin	DMD3XMW	Spinal cord injury	ND51.2	Phase 1/2	[15]
Y-39983	DMXSEHF	Glaucoma/ocular hypertension	9C61	Phase 1/2	[16]
STM 434	DMDF29A	Ovarian cancer	2C73	Phase 1	[17]
AT13148	DMYIPKJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[18]
Hexahydro azepinone derivative 1	DMC1ZIX	N. A.	N. A.	Patented	[17]
Isoquinoline sulfonyl derivative 2	DMT5E7M	N. A.	N. A.	Patented	[17]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Norepinephrine transporter (NET)	TTAWNKZ	SC6A2_HUMAN	Modulator	[2]
Rho-associated protein kinase (ROCK)	TTMQO60	NOUNIPROTAC	Modulator	[2]

References

• [1] ClinicalTrials.gov (NCT02558400) Double-masked Study of PG324 Ophthalmic Solution in Patients With Glaucoma or Ocular Hypertension.
• [2] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [3] Augmentation effect of combination therapy of aripiprazole and antidepressants on forced swimming test in mice. Psychopharmacology (Berl). 2009 Sep;206(1):97-107.
• [4] Treatment of comorbid pain with serotonin norepinephrine reuptake inhibitors. CNS Spectr. 2008 Jul;13(7 Suppl 11):22-6.
• [5] Invivo antioxidant status: a putative target of antidepressant action. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Mar 17;33(2):220-8.
• [6] Differential involvement of the norepinephrine, serotonin and dopamine reuptake transporter proteins in cocaine-induced taste aversion. Pharmacol Biochem Behav. 2009 Jul;93(1):75-81.
• [7] Clinically relevant drug interactions with new generation antidepressants and antipsychotics. Ther Umsch. 2009 Jun;66(6):485-92.
• [8] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [9] Antidepressants suppress production of the Th1 cytokine interferon-gamma, independent of monoamine transporter blockade. Eur Neuropsychopharmacol. 2006 Oct;16(7):481-90.
• [10] Multi-target therapeutics: when the whole is greater than the sum of the parts. Drug Discov Today. 2007 Jan;12(1-2):34-42.
• [11] 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.
• [12] Pharmacological properties of Y-27632, a specific inhibitor of rho-associated kinases. Mol Pharmacol. 2000 May;57(5):976-83.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Rho kinase inhibitors: a patent review (2014 - 2016).Expert Opin Ther Pat. 2017 Apr;27(4):507-515.
• [18] Company report (Astex)