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

General Information of Drug (ID: DMHYORU)

• Drug Name: UCB-101333-3 Drug Info
• Synonyms: UCB-101333-3; CHEMBL205654; SCHEMBL460823; XMDRTFUFPOAGDR-UHFFFAOYSA-N; BDBM50181089; 6-(1-azepanyl)-N,2-dicyclopropyl-5-methyl-4-pyrimidinamine

Indication

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

• Cross-matching ID:
  PubChem CID: 10125445
  TTD Drug ID: DMHYORU

Molecule-Related Drug Atlas

Drug(s) Targeting Phosphodiesterase 4D (PDE4D)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Papaverine	DMCA9QP	Brain ischaemia	8B1Z	Approved	[3]
DENBUFYLLINE	DM2R15Q	Cognitive impairment	6D71	Phase 3	[4]
SOTB07	DMIG4OX	Asthma	CA23	Phase 3	[5]
AN-2898	DMDK7CL	Atopic dermatitis	EA80	Phase 2	[6]
GPD-1116	DMOQ7YI	Asthma	CA23	Phase 2	[7]
TA-7906	DMZTAJL	Atopic dermatitis	EA80	Phase 2	[8]
HT-0712	DM2WP8F	Cognitive impairment	6D71	Phase 2	[5]
TOFIMILAST	DMLCUAS	Chronic obstructive pulmonary disease	CA22	Phase 2	[9]
AWD-12-281	DMVADGZ	Rhinitis	FA20	Phase 2	[10]
LIRIMILAST	DMD4KAU	Chronic obstructive pulmonary disease	CA22	Phase 2	[9]

Drug(s) Targeting Phosphodiesterase 4B (PDE4B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
DENBUFYLLINE	DM2R15Q	Cognitive impairment	6D71	Phase 3	[4]
SOTB07	DMIG4OX	Asthma	CA23	Phase 3	[11]
BI 1015550	DM6DO2P	Idiopathic pulmonary fibrosis	CB03.4	Phase 3	[12]
AN-2898	DMDK7CL	Atopic dermatitis	EA80	Phase 2	[6]
GPD-1116	DMOQ7YI	Asthma	CA23	Phase 2	[7]
TA-7906	DMZTAJL	Atopic dermatitis	EA80	Phase 2	[8]
HT-0712	DM2WP8F	Cognitive impairment	6D71	Phase 2	[11]
TOFIMILAST	DMLCUAS	Chronic obstructive pulmonary disease	CA22	Phase 2	[13]
AWD-12-281	DMVADGZ	Rhinitis	FA20	Phase 2	[10]
LIRIMILAST	DMD4KAU	Chronic obstructive pulmonary disease	CA22	Phase 2	[13]

Drug(s) Targeting Phosphodiesterase 4A (PDE4A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dyphylline	DM8DZC1	Acute bronchial asthma	CA23	Approved	[14]
Enprofylline	DMFYZKN	Asthma	CA23	Approved	[15]
DENBUFYLLINE	DM2R15Q	Cognitive impairment	6D71	Phase 3	[4]
SOTB07	DMIG4OX	Asthma	CA23	Phase 3	[16]
Tofisopam	DMTGNWU	Hyperuricaemia	5C55.Y	Phase 2	[17]
AN-2898	DMDK7CL	Atopic dermatitis	EA80	Phase 2	[6]
GPD-1116	DMOQ7YI	Asthma	CA23	Phase 2	[7]
TA-7906	DMZTAJL	Atopic dermatitis	EA80	Phase 2	[8]
HT-0712	DM2WP8F	Cognitive impairment	6D71	Phase 2	[16]
TOFIMILAST	DMLCUAS	Chronic obstructive pulmonary disease	CA22	Phase 2	[18]

Drug(s) Targeting Muscarinic acetylcholine receptor M3 (CHRM3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tolterodine	DMSHPW8	Overactive bladder	GC50.0	Approved	[19]
ACECLIDINE	DMOLNCZ	Glaucoma/ocular hypertension	9C61	Approved	[20]
Tiotropium	DMFDC0Q	Chronic obstructive pulmonary disease	CA22	Approved	[21]
Ipratropium	DMFQ320	Obstructive lung disease	CA22.Z	Approved	[22]
Darifenacin	DMWXLYZ	Overactive bladder	GC50.0	Approved	[23]
Methacholine Chloride	DMGS4QH	Asthma	CA23	Approved	[24]
SMT-D002	DM1I93C	Seborrhea	ED91.2	Approved	[25]
Solifenacin	DMG592Q	Overactive bladder	GC50.0	Approved	[26]
Methylscopolamine	DM5VWOB	Peptic ulcer	DA61	Approved	[27]
Cevimeline	DMWSMND	Sjogren syndrome	4A43.20	Approved	[28]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Muscarinic acetylcholine receptor M3 (CHRM3)	TTQ13Z5	ACM3_HUMAN	Inhibitor	[1]
Phosphodiesterase 4A (PDE4A)	TTZ97H5	PDE4A_HUMAN	Inhibitor	[2]
Phosphodiesterase 4B (PDE4B)	TTVIAT9	PDE4B_HUMAN	Inhibitor	[2]
Phosphodiesterase 4D (PDE4D)	TTSKMI8	PDE4D_HUMAN	Inhibitor	[2]

References

• [1] Dual M3 antagonists-PDE4 inhibitors. Part 2: Synthesis and SAR of 3-substituted azetidinyl derivatives. Bioorg Med Chem Lett. 2007 Jun 1;17(11):3077-80.
• [2] First dual M3 antagonists-PDE4 inhibitors: synthesis and SAR of 4,6-diaminopyrimidine derivatives. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1834-9.
• [3] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [4] Pyrazolopyrimidine-2,4-dione sulfonamides: novel and selective calcitonin inducers. J Med Chem. 2002 May 23;45(11):2342-5.
• [5] 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: 1303).
• [6] An assessment of the genetic toxicology of novel boron-containing therapeutic agents. Environ Mol Mutagen. 2013 Jun;54(5):338-46.
• [7] Phosphodiesterase 4 inhibitor GPD-1116 markedly attenuates the development of cigarette smoke-induced emphysema in senescence-accelerated mice P1 s... Am J Physiol Lung Cell Mol Physiol. 2008 Feb;294(2):L196-204.
• [8] Potential role of phosphodiesterase 7 in human T cell function: comparative effects of two phosphodiesterase inhibitors. Clin Exp Immunol. 2002 Jun;128(3):460-6.
• [9] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [10] The phosphodiesterase 4 inhibitor AWD 12-281 is active in a new guinea-pig model of allergic skin inflammation predictive of human skin penetration and suppresses both Th1 and Th2 cytokines in mice. J Pharm Pharmacol. 2005 Dec;57(12):1609-17.
• [11] 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: 1301).
• [12] BI 1015550 is a PDE4B Inhibitor and a Clinical Drug Candidate for the Oral Treatment of Idiopathic Pulmonary Fibrosis. Front Pharmacol. 2022 Apr 20;13:838449.
• [13] Therapeutic target database update 2012: a resource for facilitating target-oriented drug discovery. Nucleic Acids Res. 2012 Jan;40(Database issue):D1128-36.
• [14] Ocular hypotension induced by topical dopaminergic drugs and phosphodiesterase inhibitors. Eur J Pharmacol. 1994 Jun 2;258(1-2):85-94.
• [15] Effects of enprofylline, a new xanthine derivate, on human pregnant myometrium. Am J Obstet Gynecol. 1987 Apr;156(4):958-62.
• [16] 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: 1300).
• [17] The atypical anxiolytic drug, tofisopam, selectively blocks phosphodiesterase isoenzymes and is active in the mouse model of negative symptoms of psychosis. J Neural Transm (Vienna). 2010 Nov;117(11):1319-25.
• [18] GSK256066, an exceptionally high-affinity and selective inhibitor of phosphodiesterase 4 suitable for administration by inhalation: in vitro, kinetic, and in vivo characterization. J Pharmacol Exp Ther. 2011 Apr;337(1):145-54.
• [19] Signal transduction underlying carbachol-induced contraction of human urinary bladder. J Pharmacol Exp Ther. 2004 Jun;309(3):1148-53.
• [20] Design, synthesis, and neurochemical evaluation of 5-(3-alkyl-1,2,4- oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidines as M1 muscarinic receptor agonists. J Med Chem. 1993 Apr 2;36(7):842-7.
• [21] DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6.
• [22] Role of parasympathetic nerves and muscarinic receptors in allergy and asthma.Chem Immunol Allergy.2012;98:48-69.
• [23] M(1) and M(3) muscarinic receptors are involved in the release of urinary bladder-derived relaxant factor. Pharmacol Res. 2009 May;59(5):300-5.
• [24] Muscarinic M3-receptors mediate cholinergic synergism of mitogenesis in airway smooth muscle. Am J Respir Cell Mol Biol. 2003 Feb;28(2):257-62.
• [25] Demonstration of bladder selective muscarinic receptor binding by intravesical oxybutynin to treat overactive bladder. J Urol. 2004 Nov;172(5 Pt 1):2059-64.
• [26] Comparison of muscarinic receptor selectivity of solifenacin and oxybutynin in the bladder and submandibular gland of muscarinic receptor knockout ... Eur J Pharmacol. 2009 Aug 1;615(1-3):201-6.
• [27] Interaction of neuromuscular blocking drugs with recombinant human m1-m5 muscarinic receptors expressed in Chinese hamster ovary cells. Br J Pharmacol. 1998 Nov;125(5):1088-94.
• [28] Degradation of submandibular gland AQP5 by parasympathetic denervation of chorda tympani and its recovery by cevimeline, an M3 muscarinic receptor ... Am J Physiol Gastrointest Liver Physiol. 2008 Jul;295(1):G112-G123.