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

General Information of Drug (ID: DMERM0K)

• Drug Name: RS-8359 Drug Info
• Synonyms: CS-8359; TUK-9261; TUK-9262; TUK-9508

Indication

Disease Entry	ICD 11	Status	REF
Major depressive disorder	6A70.3	Discontinued in Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 164116
  CAS Number: CAS 105365-76-2
  TTD Drug ID: DMERM0K
  INTEDE Drug ID: DR1785

Molecule-Related Drug Atlas

Drug(s) Targeting Monoamine oxidase type A (MAO-A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Moclobemide	DMNZWL7	Depression	6A70-6A7Z	Approved	[4]
Tranylcypromine	DMGB5RE	Major depressive disorder	6A70.3	Approved	[5]
Clorgyline	DMCEUJD	Parkinson disease	8A00.0	Approved	[6]
Isocarboxazid	DMAF1NB	Depression	6A70-6A7Z	Approved	[7]
TRYPTAMINE	DMAFPHB	N. A.	N. A.	Phase 3	[8]
Psoralen	DMIZJ8M	N. A.	N. A.	Phase 3	[9]
CHF-3381	DMQ2O8V	Neuropathic pain	8E43.0	Phase 2	[10]
Ladostigil	DMJSY3Q	Alzheimer disease	8A20	Phase 2	[11]
CX157	DMS2WB5	Mood disorder	6A60-6E23	Phase 2	[12]
PIPERINE	DMYEAB1	Vitiligo	ED63.0	Phase 1/2	[13]

Drug(s) Metabolized By Cytochrome P450 3A4 (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[14]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[15]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[16]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[17]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[18]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[19]
Etoposide	DMNH3PG	Acute myelogenous leukaemia	2A41	Approved	[20]
Zidovudine	DM4KI7O	Human immunodeficiency virus infection	1C62	Approved	[21]
Prasterone	DM67VKL	Chronic obstructive pulmonary disease	CA22	Approved	[15]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[22]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Monoamine oxidase type A (MAO-A)	TT3WG5C	AOFA_HUMAN	Inhibitor	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4) Main DME	DE4LYSA	CP3A4_HUMAN	Substrate	[3]

References

• [1] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000633)
• [2] Stereospecific oxidation of the (S)-enantiomer of RS-8359, a selective and reversible monoamine oxidase A (MAO-A) inhibitor, by aldehyde oxidase. Xenobiotica. 2005 Jun;35(6):561-73.
• [3] Stereoselective pharmacokinetics of RS-8359, a selective and reversible MAO-A inhibitor, by species-dependent drug-metabolizing enzymes. Chirality. 2005 Mar;17(3):135-41.
• [4] Efficacy of citalopram and moclobemide in patients with social phobia: some preliminary findings. Hum Psychopharmacol. 2002 Dec;17(8):401-5.
• [5] Tramadol and another atypical opioid meperidine have exaggerated serotonin syndrome behavioural effects, but decreased analgesic effects, in genetically deficient serotonin transporter (SERT) mice. Int J Neuropsychopharmacol. 2009 Mar 11:1-11.
• [6] Further investigation into the mechanism of tachykinin NK(2) receptor-triggered serotonin release from guinea-pig proximal colon. J Pharmacol Sci. 2009 May;110(1):122-6.
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• [8] Binding of beta-carbolines at imidazoline I2 receptors: a structure-affinity investigation. Bioorg Med Chem Lett. 2004 Feb 23;14(4):999-1002.
• [9] Inhibition of rat brain monoamine oxidase activities by psoralen and isopsoralen: implications for the treatment of affective disorders. Pharmacol Toxicol. 2001 Feb;88(2):75-80.
• [10] Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
• [11] Ladostigil: a novel multimodal neuroprotective drug with cholinesterase and brain-selective monoamine oxidase inhibitory activities for Alzheimer's disease treatment. Curr Drug Targets. 2012 Apr;13(4):483-94.
• [12] Reversible inhibitors of monoamine oxidase-A (RIMAs): robust, reversible inhibition of human brain MAO-A by CX157. Neuropsychopharmacology. 2010 Feb;35(3):623-31.
• [13] Proposed structural basis of interaction of piperine and related compounds with monoamine oxidases. Bioorg Med Chem Lett. 2010 Jan 15;20(2):537-40.
• [14] Expression levels and activation of a PXR variant are directly related to drug resistance in osteosarcoma cell lines. Cancer. 2007 Mar 1;109(5):957-65.
• [15] Contribution of human hepatic cytochrome P450 isoforms to regioselective hydroxylation of steroid hormones. Xenobiotica. 1998 Jun;28(6):539-47.
• [16] Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75.
• [17] Isoform-specific regulation of cytochromes P450 expression by estradiol and progesterone. Drug Metab Dispos. 2013 Feb;41(2):263-9.
• [18] Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
• [19] Potent mechanism-based inhibition of CYP3A4 by imatinib explains its liability to interact with CYP3A4 substrates. Br J Pharmacol. 2012 Apr;165(8):2787-98.
• [20] Effects of morin on the pharmacokinetics of etoposide in rats. Biopharm Drug Dispos. 2007 Apr;28(3):151-6.
• [21] The metabolism of zidovudine by human liver microsomes in vitro: formation of 3'-amino-3'-deoxythymidine. Biochem Pharmacol. 1994 Jul 19;48(2):267-76.
• [22] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.