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

General Information of Drug (ID: DMZUAJ4)

• Drug Name: PMX-53 Drug Info
• Synonyms: YOKBGCTZYPOSQM-HPSWDUTRSA-N; PMX53; CHEMBL41547; (2S)-2-acetamido-N-[(3S,9S,12S,15R,18S)-15-(cyclohexylmethyl)-9-[3-(diaminomethylideneamino)propyl]-12-(1H-indol-3-ylmethyl)-2,8,11,14,17-pentaoxo-1,7,10,13,16-pentazabicyclo[1630]henicosan-3-yl]-3-phenylpropanamide; PMX 53; AcF-[OP(D-Cha)WR]; Ac-Phe-[Orn-Pro-cha-Trp-Arg]; C5aR-AP; AC1OCFH0; GTPL579; SCHEMBL16492460; SCHEMBL12971688; 219639-75-5; BDBM50111445; AcF-[OP(D-Cha)WR]; N-Acetyl-L-phenylalanyl-L-ornithyl-L-prolyl-3-cyclohexyl-D-alanyl-L-tryptophyl-D-arginine N-52-C-16-lactam

Indication

Disease Entry	ICD 11	Status	REF
Atopic dermatitis	EA80	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 6918468
  TTD Drug ID: DMZUAJ4

Molecule-Related Drug Atlas

Drug(s) Targeting C5a anaphylatoxin chemotactic receptor (C5AR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Avacopan	DM5LQHB	Anca-associated vasculitis	4A44.A	Approved	[4]
NN8209	DM2TDE7	Rheumatoid arthritis	FA20	Discontinued in Phase 2	[5]
NN8210	DM8Z5VH	Rheumatoid arthritis	FA20	Discontinued in Phase 1	[5]
PMX205	DMMXR3L	Central nervous system disease	8A04-8D87	Preclinical	[6]
RPR121154	DM9DXHM	Discovery agent	N.A.	Investigative	[7]
W54011	DMQI7BA	Discovery agent	N.A.	Investigative	[8]
C5aR pepducins	DMEK4HZ	Inflammation	1A00-CA43.1	Investigative	[7]
NDT9520492	DMFKX7Z	Discovery agent	N.A.	Investigative	[9]

Drug(s) Targeting Albendazole monooxygenase (CYP3A4)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Curcumin	DMQPH29	Solid tumour/cancer	2A00-2F9Z	Phase 3	[10]
BMS-536924	DMXJB4N	Discovery agent	N.A.	Investigative	[11]
Heme	DMGC287	Discovery agent	N.A.	Investigative	[12]
ML-3163	DM3S5UC	Discovery agent	N.A.	Investigative	[13]
6-(3-Hydroxy-phenyl)-naphthalen-2-ol	DMH8WA2	Discovery agent	N.A.	Investigative	[14]
2-(2-(4-tert-Butylphenylthio)ethyl)-1H-imidazole	DMZVBPG	Discovery agent	N.A.	Investigative	[15]
ML-3375	DMXJY6W	Discovery agent	N.A.	Investigative	[13]
ML-3403	DMTQWI8	Discovery agent	N.A.	Investigative	[13]
4-[5-(3-Hydroxyphenyl)-3-thienyl]-2-methylphenol	DM7ERYJ	Discovery agent	N.A.	Investigative	[16]
2-Fluoro-4-[5-(3-hydroxyphenyl)-2-thienyl]phenol	DMUGAT8	Discovery agent	N.A.	Investigative	[16]

Drug(s) Targeting Substance-K receptor (TACR2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ibodutant	DMT67EH	Irritable bowel syndrome	DD91.0	Phase 3	[17]
Rambazole	DMP2DNS	Psoriasis vulgaris	EA90	Phase 2	[18]
Nepadutant	DMPMF6L	Infantile colics	DD93.1	Phase 1/2	[19]
Saredutant	DMSRJY3	Anxiety disorder	6B00-6B0Z	Discontinued in Phase 3	[20]
CS-003	DM1AEVT	Chronic obstructive pulmonary disease	CA22	Discontinued in Phase 2	[21]
FK-224	DM1JUS0	Asthma	CA23	Discontinued in Phase 2	[22]
DNK-333	DM4ZO01	Irritable bowel syndrome	DD91.0	Discontinued in Phase 2	[23]
AVE-5883	DM3P84V	Asthma	CA23	Discontinued in Phase 1/2	[24]
UK-224671	DMDTRJB	Urinary incontinence	MF50.2	Discontinued in Phase 1	[25]
SR 144190	DMK4XT8	Acute or chronic pain	MG30-MG31	Discontinued in Phase 1	[26]

Drug(s) Targeting Nociceptin receptor (OPRL1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SER-100	DMDW5ZC	Heart failure	BD10-BD13	Phase 2	[27]
BTRX-246040	DMA9238	Major depressive disorder	6A70.3	Phase 2	[28]
LY-2940094	DMB5L6Q	Major depressive disorder	6A70.3	Phase 2	[29]
NOCICEPTIN	DMUPA7C	Headache	8A80-8A84	Phase 1	[30]
JTC-801	DMV3UN4	Pain	MG30-MG3Z	Discontinued in Phase 2	[31]
ND1251	DMMLESX	Depression	6A70-6A7Z	Discontinued in Phase 1	[32]
ATI-17000	DMZJVR5	Irritable bowel syndrome	DD91.0	Preclinical	[33]
4-phenyl-1-(1-phenylbutyl)piperidin-4-ol	DMVCIJB	Discovery agent	N.A.	Investigative	[34]
1-(dio-tolylmethyl)-4-phenylpiperidin-4-ol	DMLYO8P	Discovery agent	N.A.	Investigative	[34]
1-benzhydryl-4-ethoxy-4-phenylpiperidine	DM6PIL2	Discovery agent	N.A.	Investigative	[34]

Drug(s) Targeting Melanocortin receptor 4 (MC4R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methylnaltrexone bromide	DMZTGN2	Opioid-induced constipation	DB32.1	Approved	[35]
Bremelanotide	DM20LIM	Hypoactive sexual desire dysfunction	HA00	Approved	[36]
Setmelanotide	DMPVRN9	Obesity	5B81	Approved	[37]
Amylin	DMWDEN0	N. A.	N. A.	Phase 4	[38]
AMG 386	DMQJXL4	Breast cancer	2C60-2C65	Phase 3	[35]
PF-446687	DML38VU	Female sexual arousal dysfunction	HA01.1	Phase 2	[39]
AP-1030	DMBGA35	Metabolic disorder	5C50-5D2Z	Phase 1/2	[40]
PF-07258669	DM3CJ5N	Malnutrition	5B50-5B71	Phase 1	[41]
PT-14	DMYM9JL	Erectile dysfunction	HA01.1	Discontinued in Phase 2	[42]
Melanotetan II	DMYK8MV	Obesity	5B81	Preclinical	[35]

Drug(s) Targeting Vasopressin V1a receptor (V1AR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Desmopressin	DMS3GVE	Diabetic complication	5A2Y	Approved	[43]
Mozavaptan	DMZ905C	Hyponatraemia	5C72	Approved	[44]
Oxytocin	DMDL27I	Autism spectrum disorder	6A02	Approved	[45]
Conivaptan	DM1V329	Euvolemic hyponatremia	5C72	Approved	[46]
Felypressin	DMHLP9C	Localisation	N.A.	Approved	[47]
Terlipressin	DMT9FH3	Hypertension	BA00-BA04	Approved	[48]
ATOSIBAN	DMB7WYM	N. A.	N. A.	Phase 4	[49]
Balovaptan	DMKMTDG	Autism spectrum disorder	6A02	Phase 3	[50]
SSR149415	DMCMD93	Anxiety disorder	6B00-6B0Z	Phase 2	[51]
VA-111913	DMAYWXD	Dysmenorrhea	GA34.3	Phase 2	[52]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Albendazole monooxygenase (CYP3A4)	TTXV4FI	CP3A4_HUMAN	Inhibitor	[2]
C5a anaphylatoxin chemotactic receptor (C5AR1)	TTHXFA1	C5AR1_HUMAN	Modulator	[3]
Melanocortin receptor 4 (MC4R)	TTD0CIQ	MC4R_HUMAN	Inhibitor	[2]
Nociceptin receptor (OPRL1)	TTNT7K8	OPRX_HUMAN	Inhibitor	[2]
Substance-K receptor (TACR2)	TTYO0A3	NK2R_HUMAN	Inhibitor	[2]
Vasopressin V1a receptor (V1AR)	TT4TFGN	V1AR_HUMAN	Inhibitor	[2]

References

• [1] 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. (Ligand id: 579).
• [2] Peptidomimetic C5a receptor antagonists with hydrophobic substitutions at the C-terminus: increased receptor specificity and in vivo activity. Bioorg Med Chem Lett. 2006 Oct 1;16(19):5088-92.
• [3] Company report (Arana Therapeutics)
• [4] Clinical pipeline report, company report or official report of ChemoCentryx.
• [5] Complement in immune and inflammatory disorders: therapeutic interventions. J Immunol. 2013 Apr 15;190(8):3839-47.
• [6] Development and validation of a LC-MS/MS assay for pharmacokinetic studies of complement C5a receptor antagonists PMX53 and PMX205 in mice. Sci Rep. 2018 May 25;8(1):8101.
• [7] 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: 32).
• [8] Identification of a potent and orally active non-peptide C5a receptor antagonist. J Biol Chem. 2002 Dec 20;277(51):49403-7.
• [9] Molecular characterization of the gerbil C5a receptor and identification of a transmembrane domain V amino acid that is crucial for small molecule ... J Biol Chem. 2005 Dec 9;280(49):40617-23.
• [10] Structure-activity relationships for the inhibition of recombinant human cytochromes P450 by curcumin analogues. Eur J Med Chem. 2008 Aug;43(8):1621-31.
• [11] Discovery and evaluation of 4-(2-(4-chloro-1H-pyrazol-1-yl)ethylamino)-3-(6-(1-(3-fluoropropyl)piperidin-4-yl)-4-methyl-1H-benzo[d]imidazol-2-yl)py... J Med Chem. 2008 Oct 9;51(19):5897-900.
• [12] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [13] 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.
• [14] Design, synthesis, and biological evaluation of (hydroxyphenyl)naphthalene and -quinoline derivatives: potent and selective nonsteroidal inhibitors... J Med Chem. 2008 Apr 10;51(7):2158-69.
• [15] 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.
• [16] 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.
• [17] Antagonist profile of ibodutant at the tachykinin NK2 receptor in guinea pig isolated bronchi. Eur J Pharmacol. 2013 Nov 15;720(1-3):180-5.
• [18] Pharmacology of an original and selective nonpeptide antagonist ligand for the human tachykinin NK2 receptor. Eur J Pharmacol. 2005 Jun 1;516(2):104-11.
• [19] Emerging drugs for postoperative ileus. Expert Opin Emerg Drugs. 2007 Nov;12(4):619-26.
• [20] Characterization of species-related differences in the pharmacology of tachykinin NK receptors 1, 2 and 3. Biochem Pharmacol. 2009 May 1;77(9):1522-30.
• [21] Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
• [22] Effects of FK224, a novel compound NK1 and NK2 receptor antagonist, on airway constriction and airway edema induced by neurokinins and sensory nerv... J Pharmacol Exp Ther. 1992 Jul;262(1):403-8.
• [23] Dual tachykinin NK1/NK2 antagonist DNK333 inhibits neurokinin A-induced bronchoconstriction in asthma patients. Eur Respir J. 2004 Jan;23(1):76-81.
• [24] Effect of an NK1/NK2 receptor antagonist on airway responses and inflammation to allergen in asthma. Am J Respir Crit Care Med. 2007 Mar 1;175(5):450-7.
• [25] Pharmacokinetics and metabolism of a sulphamide NK2 antagonist in rat, dog and human. Xenobiotica. 2000 Jun;30(6):627-42.
• [26] Pharmacologic evaluation of neurokinin-2 receptor antagonists in the guinea pig respiratory tract. Am J Vet Res. 2004 Jul;65(7):984-91.
• [27] Clinical pipeline report, company report or official report of Serodus ASA.
• [28] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [29] Emerging mechanisms and treatments for depression beyond SSRIs and SNRIs. Biochemical Pharmacology Volume 95, Issue 2, 15 May 2015, Pages 81-97.
• [30] Binding and in vitro activities of peptides with high affinity for the nociceptin/orphanin FQ receptor, ORL1. J Pharmacol Exp Ther. 1997 Nov;283(2):735-41.
• [31] Nociceptin receptor antagonist JTC-801 inhibits nitrous oxide-induced analgesia in mice. J Anesth. 2009;23(2):301-3.
• [32] The nociceptin receptor as a potential target in drug design. Drug News Perspect. 2001 Aug;14(6):335-45.
• [33] Nocistatin and nociceptin given centrally induce opioid-mediated gastric mucosal protection. Peptides. 2008 Dec;29(12):2257-65.
• [34] Bioorg Med Chem Lett. 2007 Jun 1;17(11):3023-7. Epub 2007 Mar 23.Synthesis and structure-activity relationships of 4-hydroxy-4-phenylpiperidines as nociceptin receptor ligands: Part 1.
• [35] Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
• [36] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [37] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
• [38] Novel anti-obesity drugs. Expert Opin Investig Drugs. 2000 Jun;9(6):1317-26.
• [39] Melanocortin Receptor Agonists Facilitate Oxytocin-Dependent Partner Preference Formation in the Prairie Vole. Neuropsychopharmacology. 2015 Jul;40(8):1856-65.
• [40] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [41] Discovery of the Potent and Selective MC4R Antagonist PF-07258669 for the Potential Treatment of Appetite Loss. J Med Chem. 2023 Mar 9;66(5):3195-3211.
• [42] The protective effects of the melanocortin receptor (MCR) agonist, melanotan-II (MTII), against binge-like ethanol drinking are facilitated by deletion of the MC3 receptor in mice. Neuropeptides. 2014 Feb;48(1):47-51.
• [43] Design of potent and selective agonists for the human vasopressin V1b receptor based on modifications of [deamino-cys1]arginine vasopressin at position 4. J Med Chem. 2004 Apr 22;47(9):2375-88.
• [44] Nonpeptide vasopressin antagonists: a new group of hormone blockers entering the scene. Exp Clin Endocrinol Diabetes. 1999;107(3):157-65.
• [45] Mapping peptide-binding domains of the human V1a vasopressin receptor with a photoactivatable linear peptide antagonist. J Biol Chem. 1997 Oct 17;272(42):26536-44.
• [46] Acute hemodynamic effects of conivaptan, a dual V(1A) and V(2) vasopressin receptor antagonist, in patients with advanced heart failure. Circulation. 2001 Nov 13;104(20):2417-23.
• [47] Peptide and non-peptide agonists and antagonists for the vasopressin and oxytocin V1a, V1b, V2 and OT receptors: research tools and potential therapeutic agents. Prog Brain Res. 2008;170:473-512.
• [48] Investigational vasopressin receptor modulators in the pipeline. Expert Opin Investig Drugs. 2009 Aug;18(8):1119-31.
• [49] The discovery of GSK221149A: a potent and selective oxytocin antagonist. Bioorg Med Chem Lett. 2008 Jan 1;18(1):90-4.
• [50] Discovery of Balovaptan, a Vasopressin 1a Receptor Antagonist for the Treatment of Autism Spectrum Disorder. J Med Chem. 2020 Feb 27;63(4):1511-1525.
• [51] Tetrahydroquinoline sulfonamides as vasopressin 1b receptor antagonists. Bioorg Med Chem Lett. 2009 Nov 1;19(21):6018-22.
• [52] Clinical pipeline report, company report or official report of Avarx.