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

General Information of Drug (ID: DM0XDG6)

• Drug Name: 4-(Spiro[chromene-2,4'-piperidine]-4-yl)benzamide Drug Info
• Synonyms: CHEMBL550063; SCHEMBL10266987; BDBM50297313

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 44254503
  TTD Drug ID: DM0XDG6

Molecule-Related Drug Atlas

Drug(s) Targeting Voltage-gated potassium channel Kv11.1 (KCNH2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
VESNARINONE	DMBKX3C	Cardiac failure	BD10-BD13	Approved	[2]
M100907	DM7ZFBA	Sleep-wake disorder	7A00-7B2Z	Phase 3	[3]
HP-184	DMNOMV2	Multiple sclerosis	8A40	Phase 2	[4]
NITD609	DMQHBSX	Malaria	1F40-1F45	Phase 2	[5]
ABT-229	DMN3S1B	Pain	MG30-MG3Z	Phase 2	[6]
ISOQUINE	DMR17YI	Malaria	1F40-1F45	Phase 1	[7]
Pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrazine derivative 1	DMC8935	N. A.	N. A.	Patented	[8]
Isoindoline derivative 5	DMIUTQW	N. A.	N. A.	Patented	[9]
Isoindoline derivative 3	DM2MYL9	N. A.	N. A.	Patented	[9]
Isoindoline derivative 4	DMP1NKI	N. A.	N. A.	Patented	[9]

Drug(s) Targeting Opioid receptor mu (MOP)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Buprenorphine	DMPRI8G	Opioid dependence	6C43.2Z	Approved	[10]
Morphine	DMRMS0L	Advanced cancer	2A00-2F9Z	Approved	[11]
Hydromorphone	DMHP21E	Back pain	ME84.Z	Approved	[12]
Tapentadol hydrochloride	DMXLSH3	Acute pain	MG31	Approved	[13]
Fentanyl	DM8WAHT	Analgesia	MB40.8	Approved	[14]
Alfentanil	DMVO0UB	Anaesthesia	9A78.6	Approved	[15]
Naloxegol	DML0B41	Opioid-induced constipation	DB32.1	Approved	[16]
Eluxadoline	DMYZ0P1	Diarrhea-predominant irritable bowel syndrome	DD91.01	Approved	[17]
Nalfurafine hcl	DMA9DHW	Uremic pruritus	EC90.10	Approved	[18]
Oxycodone	DMXLKHV	Osteoarthritis	FA00-FA05	Approved	[19]

Drug(s) Targeting Debrisoquine 4-hydroxylase (CYP2D6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Glutethimide	DMGE0CW	Insomnia	7A00-7A0Z	Approved	[20]
ISOQUINE	DMR17YI	Malaria	1F40-1F45	Phase 1	[7]
ICI-199441	DMEWZ80	Discovery agent	N.A.	Investigative	[21]
ML-3163	DM3S5UC	Discovery agent	N.A.	Investigative	[22]
2-(2-(4-tert-Butylphenylthio)ethyl)-1H-imidazole	DMZVBPG	Discovery agent	N.A.	Investigative	[23]
4-[5-(3-Hydroxyphenyl)-3-thienyl]-2-methylphenol	DM7ERYJ	Discovery agent	N.A.	Investigative	[24]
2-Fluoro-4-[5-(3-hydroxyphenyl)-2-thienyl]phenol	DMUGAT8	Discovery agent	N.A.	Investigative	[24]
4-[5-(3-Hydroxyphenyl)-2-thienyl)-2-methyl]phenol	DMK4ICB	Discovery agent	N.A.	Investigative	[24]
4-[2-(4-Imidazol-1-yl-phenoxy)-ethyl]-morpholine	DM9UGO0	Discovery agent	N.A.	Investigative	[25]
DIHYDROCUBEBIN	DMZL7R6	Discovery agent	N.A.	Investigative	[26]

Drug(s) Targeting Opioid receptor delta (OPRD1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Codeine	DMJX6ZG	Allergic rhinitis	CA08.0	Approved	[27]
Hydromorphone	DMHP21E	Back pain	ME84.Z	Approved	[28]
Loperamide	DMOJZQ9	Diarrhea	ME05.1	Approved	[29]
Eluxadoline	DMYZ0P1	Diarrhea-predominant irritable bowel syndrome	DD91.01	Approved	[17]
Oxycodone	DMXLKHV	Osteoarthritis	FA00-FA05	Approved	[30]
Butorphanol	DM5KYPJ	Pain	MG30-MG3Z	Approved	[27]
Carfentanil	DM7ADGX	N. A.	N. A.	Phase 2	[31]
Met-enkephalin	DMSZFTP	Pain	MG30-MG3Z	Phase 2	[32]
AZD-2327	DM8FZOG	Anxiety disorder	6B00-6B0Z	Phase 2	[33]
ADL-5747	DMMUPTN	Pain	MG30-MG3Z	Phase 2	[34]

Drug(s) Targeting Opioid receptor kappa (OPRK1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nalbuphine	DMOSQGU	Pain	MG30-MG3Z	Approved	[35]
Nalfurafine hcl	DMA9DHW	Uremic pruritus	EC90.10	Approved	[18]
CHLOROXINE	DMFZBMQ	Erythema	ME64.0	Approved	[36]
Difelikefalin	DMHZBEO	Pruritus	EC90	Approved	[37]
Dezocine	DMJDB0Y	Pain	MG30-MG3Z	Approved	[38]
Asimadoline	DMND3AB	Diarrhea-predominant irritable bowel syndrome	DD91.01	Phase 3	[39]
JNJ 67953964	DMJ8Y5N	Major depressive disorder	6A70.3	Phase 3	[40]
PHN-131	DM1SV8I	Pain	MG30-MG3Z	Phase 2/3	[41]
CR-845	DMJYTUQ	Pain	MG30-MG3Z	Phase 2/3	[42]
Carfentanil	DM7ADGX	N. A.	N. A.	Phase 2	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Debrisoquine 4-hydroxylase (CYP2D6)	TTVG215	CP2D6_HUMAN	Inhibitor	[1]
Opioid receptor delta (OPRD1)	TT27RFC	OPRD_HUMAN	Inhibitor	[1]
Opioid receptor kappa (OPRK1)	TTQW87Y	OPRK_HUMAN	Inhibitor	[1]
Opioid receptor mu (MOP)	TTKWM86	OPRM_HUMAN	Inhibitor	[1]
Voltage-gated potassium channel Kv11.1 (KCNH2)	TTQ6VDM	KCNH2_HUMAN	Inhibitor	[1]

References

• [1] Spirocyclic delta opioid receptor agonists for the treatment of pain: discovery of N,N-diethyl-3-hydroxy-4-(spiro[chromene-2,4'-piperidine]-4-yl) b... J Med Chem. 2009 Sep 24;52(18):5685-702.
• [2] Prediction of hERG potassium channel affinity by traditional and hologram qSAR methods. Bioorg Med Chem Lett. 2003 Aug 18;13(16):2773-5.
• [3] Non-basic ligands for aminergic GPCRs: the discovery and development diaryl sulfones as selective, orally bioavailable 5-HT2A receptor antagonists ... Bioorg Med Chem Lett. 2010 Jun 15;20(12):3708-12.
• [4] Emerging drugs for spinal cord injury. Expert Opin Emerg Drugs. 2008 Mar;13(1):63-80.
• [5] Spiroindolones, a potent compound class for the treatment of malaria. Science. 2010 Sep 3;329(5996):1175-80.
• [6] 9-Dihydroerythromycin ethers as motilin agonists--developing structure-activity relationships for potency and safety. Bioorg Med Chem. 2010 Nov 1;18(21):7651-8.
• [7] Candidate selection and preclinical evaluation of N-tert-butyl isoquine (GSK369796), an affordable and effective 4-aminoquinoline antimalarial for ... J Med Chem. 2009 Mar 12;52(5):1408-15.
• [8] Towards selective phosphodiesterase 2A (PDE2A) inhibitors: a patent review (2010 - present).Expert Opin Ther Pat. 2016 Aug;26(8):933-46.
• [9] The sigma-2 (-2) receptor: a review of recent patent applications: 2013-2018.Expert Opin Ther Pat. 2018 Sep;28(9):655-663.
• [10] Buprenorphine is a weak partial agonist that inhibits opioid receptor desensitization. J Neurosci. 2009 Jun 3;29(22):7341-8.
• [11] Antianalgesia: stereoselective action of dextro-morphine over levo-morphine on glia in the mouse spinal cord.J Pharmacol Exp Ther.2005 Sep;314(3):1101-8.
• [12] Clinical pipeline report, company report or official report of signaturerx.
• [13] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [14] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [15] Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain. Pain. 2001 Mar;91(1-2):177-87.
• [16] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [17] Molecular characterization of eluxadoline as a potential ligand targeting mu-delta opioid receptor heteromers.Biochem Pharmacol.2014 Dec 1;92(3):448-56.
• [18] Drug design and synthesis of a novel kappa opioid receptor agonist with an oxabicyclo[2.2.2]octane skeleton and its pharmacology. Bioorg Med Chem Lett. 2010 Jan 1;20(1):121-4.
• [19] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 319).
• [20] A study of the effects of large doses of glutethimide that were used for self-poisoning during pregnancy on human fetuses. Toxicol Ind Health. 2008 Feb-Mar;24(1-2):69-78.
• [21] Arylacetamide kappa opioid receptor agonists with reduced cytochrome P450 2D6 inhibitory activity. Bioorg Med Chem Lett. 2005 May 16;15(10):2647-52.
• [22] Novel substituted pyridinyl imidazoles as potent anticytokine agents with low activity against hepatic cytochrome P450 enzymes. J Med Chem. 2003 Jul 17;46(15):3230-44.
• [23] Role of hydrophobic substituents on the terminal nitrogen of histamine in receptor binding and agonist activity: development of an orally active hi... J Med Chem. 2010 May 13;53(9):3840-4.
• [24] New insights into the SAR and binding modes of bis(hydroxyphenyl)thiophenes and -benzenes: influence of additional substituents on 17beta-hydroxyst... J Med Chem. 2009 Nov 12;52(21):6724-43.
• [25] Imidazole derivatives as new potent and selective 20-HETE synthase inhibitors. Bioorg Med Chem Lett. 2004 Jan 19;14(2):333-6.
• [26] Potent CYP3A4 inhibitory constituents of Piper cubeba. J Nat Prod. 2005 Jan;68(1):64-8.
• [27] Butorphanol: effects of a prototypical agonist-antagonist analgesic on kappa-opioid receptors. J Pharmacol Sci. 2005 Jun;98(2):109-16.
• [28] Identification of opioid ligands possessing mixed micro agonist/delta antagonist activity among pyridomorphinans derived from naloxone, oxymorphone, and hydromorphone [correction of hydropmorphone]. J Med Chem. 2004 Mar 11;47(6):1400-12.
• [29] Loperamide: evidence of interaction with mu and delta opioid receptors. Life Sci. 1983;33 Suppl 1:315-8.
• [30] Oxycodone: a pharmacological and clinical review. Clin Transl Oncol. 2007 May;9(5):298-307.
• [31] Wax PM, Becker CE, Curry SC: Unexpected gas casualties in Moscow: a medical toxicology perspective. Ann Emerg Med. 2003 May;41(5):700-5.
• [32] Delta-opioid receptor agonists inhibit neuromuscular transmission in human colon. Eur J Pharmacol. 1994 Sep 1;262(1-2):33-9.
• [33] Preclinical pharmacology of AZD2327: a highly selective agonist of the delta-opioid receptor. J Pharmacol Exp Ther. 2011 Jul;338(1):195-204.
• [34] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 317).
• [35] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [36] In silico identification and biochemical evaluation of novel inhibitors of NRH:quinone oxidoreductase 2 (NQO2). Bioorg Med Chem Lett. 2010 Dec 15;20(24):7331-6.
• [37] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [38] Pharmacological profiles of opioid ligands at kappa opioid receptors. BMC Pharmacol. 2006 Jan 25;6:3.
• [39] Emerging drugs for irritable bowel syndrome. Expert Opin Emerg Drugs. 2006 May;11(2):293-313.
• [40] Kappa Opioid Receptor Antagonists as Potential Therapeutics for Mood and Substance Use Disorders. Handb Exp Pharmacol. 2022;271:473-491.
• [41] Nalbuphine: an autoradiographic opioid receptor binding profile in the central nervous system of an agonist/antagonist analgesic. J Pharmacol Exp Ther. 1988 Jan;244(1):391-402.
• [42] Peptide Kappa Opioid Receptor Ligands: Potential for Drug Development. AAPS J. 2009 June; 11(2): 312-322.