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

General Information of Drug (ID: DMSWLA3)

• Drug Name: Darapladib Drug Info
• Synonyms: SB 480848; Darapladib (USAN)

Indication

Disease Entry	ICD 11	Status	REF
Arteriosclerosis	BD40	Discontinued in Phase 3	[1]

• Cross-matching ID:
  PubChem CID: 9939609
  CAS Number: CAS 356057-34-6
  TTD Drug ID: DMSWLA3

Molecule-Related Drug Atlas

Drug(s) Targeting Phospholipase A2 (PLA2G1B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cholic Acid	DM7OKQV	Cholelithiasis	DC11	Approved	[4]
Miltefosine	DMND304	Chronic urticaria		Approved	[5]
Clocortolone	DM9ZMQH	Exanthem		Approved	[6]
Clobetasol	DMUXP52	Rosacea	ED90.0	Approved	[7]
Diflorasone	DMI9PRJ	Exanthem		Approved	[8]
AllerB	DM78DOT	Allergy	4A80-4A85	Phase 2b	[9]
URSOLIC ACID	DM4SOAW	Metabolic syndrome x	5C50-5D2Z	Phase 2	[10]
MANOALIDE	DMB4A8I	Arthritis	FA20	Phase 2	[11]
MRX-4	DMQZWYE	Allergic rhinitis	CA08.0	Phase 2	[12]
MRX-6	DMLVQKF	Contact dermatitis	EK0Z	Phase 2	[13]

Drug(s) Affected By Poly polymerase 1 (PARP1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[14]
Gefitinib	DM15F0X	Colon adenocarcinoma		Approved	[15]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[16]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[17]
Citalopram	DM2G9AE	Acute coronary syndrome	BA41	Approved	[18]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[19]
Imipramine	DM2NUH3	Depression	6A70-6A7Z	Approved	[18]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[20]
Sulindac	DM2QHZU	Acute myelogenous leukaemia	2A41	Approved	[21]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[22]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Phospholipase A2 (PLA2G1B)	TT9V5JH	PA21B_HUMAN	Modulator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Poly polymerase 1 (PARP1)	OT310QSG	PARP1_HUMAN	Gene/Protein Processing	[3]

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: 6696).
• [2] Darapladib, a reversible lipoprotein-associated phospholipase A2 inhibitor, for the oral treatment of atherosclerosis and coronary artery disease. IDrugs. 2009 Oct;12(10):648-55.
• [3] The selective lipoprotein-associated phospholipase A2 inhibitor darapladib triggers irreversible actions on glioma cell apoptosis and mitochondrial dysfunction. Toxicol Appl Pharmacol. 2020 Sep 1;402:115133. doi: 10.1016/j.taap.2020.115133. Epub 2020 Jul 12.
• [4] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [5] Novel antifungal agents, targets or therapeutic strategies for the treatment of invasive fungal diseases: a review of the literature (2005-2009). Rev Iberoam Micol. 2009 Mar 31;26(1):15-22.
• [6] Clocortolone pivalate: a paired comparison clinical trial of a new topical steroid in eczema/atopic dermatitis. Cutis. 1980 Jan;25(1):96-8.
• [7] Utilization of epidermal phospholipase A2 inhibition to monitor topical steroid action. Br J Dermatol. 1984 Jul;111 Suppl 27:195-203.
• [8] Structures from powders: diflorasone diacetate. Steroids. 2009 Jan;74(1):102-11.
• [9] Successful immunotherapy with T-cell epitope peptides of bee venom phospholipase A2 induces specific T-cell anergy in patients allergic to bee venom. J Allergy Clin Immunol. 1998 Jun;101(6 Pt 1):747-54.
• [10] Synthesis of benzoyl phenyl benzoates as effective inhibitors for phospholipase A2 and hyaluronidase enzymes. Bioorg Med Chem Lett. 2005 Sep 15;15(18):4100-4.
• [11] Manoalide, a phospholipase A2 inhibitor, inhibits arachidonate incorporation and turnover in brain phospholipids of the awake rat. Neurochem Res. 1998 Oct;23(10):1251-7.
• [12] Phospholipase A2, group IVA (cytosolic, calcium-dependent) (PLA2G4A). SciBX 1(41); doi:10.1038/scibx.2008.999. Nov. 13 2008
• [13] A novel treatment of contact dermatitis by topical application of phospholipase A2 inhibitor: a double-blind placebo-controlled pilot study. Int J Immunopathol Pharmacol. 2007 Jan-Mar;20(1):191-5.
• [14] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [15] Evidence of securin-mediated resistance to gefitinib-induced apoptosis in human cancer cells. Chem Biol Interact. 2013 Apr 25;203(2):412-22. doi: 10.1016/j.cbi.2013.03.011. Epub 2013 Mar 22.
• [16] Cigarette smoke and asbestos activate poly-ADP-ribose polymerase in alveolar epithelial cells. J Investig Med. 2001 Jan;49(1):68-76. doi: 10.2310/6650.2001.34092.
• [17] Apoptotic signaling pathways induced by nitric oxide in human lymphoblastoid cells expressing wild-type or mutant p53. Cancer Res. 2004 May 1;64(9):3022-9. doi: 10.1158/0008-5472.can-03-1880.
• [18] The antidepressants imipramine, clomipramine, and citalopram induce apoptosis in human acute myeloid leukemia HL-60 cells via caspase-3 activation. J Biochem Mol Toxicol. 1999;13(6):338-47. doi: 10.1002/(sici)1099-0461(1999)13:6<338::aid-jbt8>3.0.co;2-7.
• [19] Ciprofloxacin mediated cell growth inhibition, S/G2-M cell cycle arrest, and apoptosis in a human transitional cell carcinoma of the bladder cell line. Clin Cancer Res. 2000 Mar;6(3):891-900.
• [20] Investigation of molecular mechanisms underlying the antiproliferative effects of colchicine against PC3 prostate cancer cells. Toxicol In Vitro. 2021 Jun;73:105138. doi: 10.1016/j.tiv.2021.105138. Epub 2021 Mar 6.
• [21] Sulindac enhances adenoviral vector expressing mda-7/IL-24-mediated apoptosis in human lung cancer. Mol Cancer Ther. 2005 Feb;4(2):291-304.
• [22] Methotrexate induces poly(ADP-ribose) polymerase-dependent, caspase 3-independent apoptosis in subsets of proliferating CD4+ T cells. Clin Exp Immunol. 2007 May;148(2):288-95. doi: 10.1111/j.1365-2249.2007.03335.x. Epub 2007 Feb 7.