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

General Information of Drug (ID: DM3AVO1)

• Drug Name: DE-081 Drug Info
• Synonyms: Apafant; 105219-56-5; WEB-2086; Web 2086; Apafant [USAN:INN]; Apafantum [INN-Latin]; Apafanto [INN-Spanish]; WEB 2086BS; WEB2086; UNII-J613NI05SV; WEB 2086 BS; BRN 4302553; C22H22ClN5O2S; J613NI05SV; CHEMBL280164; NCGC00092377-03; NCGC00092377-02; Apafantum; Apafanto; DSSTox_CID_28900; DSSTox_RID_83168; DSSTox_GSID_48974; 4-(3-(4-(o-Chlorophenyl)-9-methyl-6H-thieno(3,2-f)-s-triazolo(4,3-a)(1,4)diazepin-2-yl)propionyl)morpholine; [3H]apafant; Morpholine; Apafant (ophthalmic formulation), Santen

Indication

Disease Entry	ICD 11	Status	REF
Conjunctivitis	9A60	Discontinued in Phase 2	[1]
Ocular allergy	4A81	Terminated	[2]

• Cross-matching ID:
  PubChem CID: 65889
  ChEBI ID: CHEBI:92490
  CAS Number: CAS 105219-56-5
  TTD Drug ID: DM3AVO1
  VARIDT Drug ID: DR01484

Molecule-Related Drug Atlas

Drug(s) Targeting Platelet-activating factor receptor (PTAFR)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ticlopidine	DMO946V	Acute coronary syndrome	BA41	Approved	[5]
RUPATADINE	DMBPN7T	N. A.	N. A.	Phase 4	[6]
ISRAPAFANT	DMP61YB	Asthma	CA23	Phase 3	[7]
CMI-392	DM1NCUY	Psoriasis vulgaris	EA90	Phase 2	[8]
Lexipafant	DMZ2YBE	Nerve injury	ND56.4	Phase 2	[9]
YM-264	DMAZNVX	Sepsis	1G40-1G41	Phase 2	[10]
Dersalazine	DMH96JW	Inflammatory bowel disease	DD72	Phase 2	[11]
60P002	DMHBN8X	Dengue	1D20-1D2Z	Phase 2	[12]
PegCNTF	DMW7VGZ	Obesity	5B81	Phase 1	[13]
FOROPAFANT	DML1DGP	Asthma	CA23	Discontinued in Phase 3	[14]

Drug(s) Transported By P-glycoprotein 1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[15]
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[16]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[17]
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[18]
Fluorouracil	DMUM7HZ	Adenocarcinoma	2D40	Approved	[17]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[17]
Progesterone	DMUY35B	Amenorrhea	GA20.0	Approved	[19]
Tamoxifen	DMLB0EZ	Breast cancer	2C60-2C65	Approved	[17]
Estradiol	DMUNTE3	Acne vulgaris	ED80	Approved	[20]
Imatinib	DM7RJXL	Acute lymphoblastic leukaemia	2A85	Approved	[21]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Platelet-activating factor receptor (PTAFR)	TTQL5VC	PTAFR_HUMAN	Modulator	[3]

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[4]

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 800000113)
• [2] 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: 1860).
• [3] Characterization of [3H]apafant binding to PAF receptor on rabbit platelet membranes: a comparison of a microplate filtration system and a standard... J Pharmacol Toxicol Methods. 1996 Sep;36(1):53-62.
• [4] Altered drug disposition of the platelet activating factor antagonist apafant in mdr1a knockout mice. Eur J Pharm Sci. 2002 Aug;16(3):119-28.
• [5] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [6] Designed multiple ligands. An emerging drug discovery paradigm. J Med Chem. 2005 Oct 20;48(21):6523-43.
• [7] Amino acid residues critical for endoplasmic reticulum export and trafficking of platelet-activating factor receptor. J Biol Chem. 2010 Feb 19;285(8):5931-40.
• [8] Anti-inflammatory activities of LDP-392, a dual PAF receptor antagonist and 5-lipoxygenase inhibitor. Pharmacol Res. 2001 Sep;44(3):213-20.
• [9] Lexipafant and acute pancreatitis: a critical appraisal of the clinical trials.Eur J Surg.2002;168(4):215-9.
• [10] Effects of YM264, a novel PAF antagonist, on puromycin aminonucleoside-induced nephropathy in the rat. Biochem Biophys Res Commun. 1991 Apr 30;176(2):781-5.
• [11] The intestinal anti-inflammatory effect of dersalazine sodium is related to a down-regulation in IL-17 production in experimental models of rodent colitis. Br J Pharmacol. 2012 February; 165(3): 729-740.
• [12] Clinical pipeline report, company report or official report of 60 Degrees Pharmaceuticals.
• [13] Sch 37370: a new drug combining antagonism of platelet-activating factor (PAF) with antagonism of histamine. Agents Actions Suppl. 1991;34:313-21.
• [14] Biochemical and pharmacological activities of SR 27417, a highly potent, long-acting platelet-activating factor receptor antagonist. J Pharmacol Exp Ther. 1991 Oct;259(1):44-51.
• [15] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [16] MDR1 (ABCB1) G1199A (Ser400Asn) polymorphism alters transepithelial permeability and sensitivity to anticancer agents. Cancer Chemother Pharmacol. 2009 Jun;64(1):183-8.
• [17] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [18] Folate transporter expression decreases in the human placenta throughout pregnancy and in pre-eclampsia. Pregnancy Hypertens. 2012 Apr;2(2):123-31.
• [19] Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res. 2001 Dec;18(12):1660-8.
• [20] Antiestrogens and steroid hormones: substrates of the human P-glycoprotein. Biochem Pharmacol. 1994 Jul 19;48(2):287-92.
• [21] Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia. Ther Drug Monit. 2011 Apr;33(2):244-50.