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

General Information of Drug (ID: DMND304)

• Drug Name: Miltefosine Drug Info
• Synonyms: HDPC; HePC; Hexadecylphosphocholine; Hexadecylphosphorylcholine; Impavido; Miltefosina; Miltefosinum; Miltex; Baxter Oncology brand of miltefosine; Baxter brand of miltefosine; Miltefosin C; Prasfarma brand of miltefosine; D 18506; IN1227; D-18506; H-1850; M-7200; Miltefosina [INN-Spanish]; Miltefosine (INN); Miltefosine[INN:BAN]; Miltefosinum [INN-Latin]; N-Hexadecylphosphorylcholine; TF-002; Choline hydroxide, hexadecyl hydrogen phosphate, inner salt; Choline, hexadecyl hydrogen phosphate, inner salt; Hexadecyl 2-(trimethylazaniumyl)ethyl phosphate; Choline phosphate, hexadecyl ester, hydroxide, inner salt; Choline phosphate, hexadecyl ester, hydroxide, inner salt (6CI); Hexadecyl 2-(trimethyl-.lambda.~5~-azanyl)ethyl hydrogen phosphate; Ethanaminium, 2-(((hexadecyloxy)hydroxyphosphinyl)oxy)-N,N,N-trimethyl-, hydroxide, inner salt; Ethanaminium, 2-(((hexadecyloxy)hydroxyphosphinyl)oxy)-N,N,N-trimethyl-, hydroxide, innner salt; 1-Hexadecylphosphorylcholine; 2-(((Hexadecyloxy)hydroxyphosphinyl)oxy)-N,N,N-trimethylethanaminium hydroxide, inner salt; 3,5-Dioxa-4-phosphaunacosan-1-aminium, 4-hydroxy-N,N,N-trimethyl-, hydroxide, inner salt, 4-oxide

Indication

Disease Entry	ICD 11	Status	REF
Chronic urticaria		Approved	[1]
Leishmaniasis	1F54	Approved	[2]
Visceral leishmaniasis	1F54.0	Phase 2	[3]

• Therapeutic Class: Antifungal Agents
• Cross-matching ID:
  PubChem CID: 3599
  ChEBI ID: CHEMBL125
  CAS Number: CAS 58066-85-6
  TTD Drug ID: DMND304
  INTEDE Drug ID: DR1092
  ACDINA Drug ID: D00436

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	[6]
Clocortolone	DM9ZMQH	Exanthem		Approved	[7]
Clobetasol	DMUXP52	Rosacea	ED90.0	Approved	[8]
Diflorasone	DMI9PRJ	Exanthem		Approved	[9]
AllerB	DM78DOT	Allergy	4A80-4A85	Phase 2b	[10]
URSOLIC ACID	DM4SOAW	Metabolic syndrome x	5C50-5D2Z	Phase 2	[11]
MANOALIDE	DMB4A8I	Arthritis	FA20	Phase 2	[12]
MRX-4	DMQZWYE	Allergic rhinitis	CA08.0	Phase 2	[13]
MRX-6	DMLVQKF	Contact dermatitis	EK0Z	Phase 2	[14]
Varespladib	DM5JJ83	Snakebite	N.A.	Phase 2	[15]

Drug(s) Affected By ATP-dependent translocase ABCB1 (ABCB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Flupentixol	DM0DJ9O	Schizophrenia	6A20	Approved	[16]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[17]
Crizotinib	DM4F29C	Non-small-cell lung cancer	2C25.Y	Approved	[18]
Lamotrigine	DM8SXYG	Bipolar disorder	6A60	Approved	[19]
Cepharanthine	DM9Y5JB	N. A.	N. A.	Approved	[20]
Itraconazole	DMCR1MV	Aspergillosis	1F20	Approved	[21]
Clozapine	DMFC71L	Schizophrenia	6A20	Approved	[22]
Midostaurin	DMI6E0R	Acute myeloid leukaemia	2A60	Approved	[23]
Trifluoperazine	DMKBYWI	Anxiety		Approved	[24]
Olanzapine	DMPFN6Y	Bipolar depression		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	Inhibitor	[3]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Choline phosphatase 1 (PLD1) Main DME	DEB2ZMT	PLD1_HUMAN	Substrate	[4]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Drug Response	[5]

References

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• [2] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [3] 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.
• [4] Development of miltefosine as an oral treatment for leishmaniasis. Trans R Soc Trop Med Hyg. 2006 Dec;100 Suppl 1:S17-20.
• [5] MDR1 causes resistance to the antitumour drug miltefosine. Br J Cancer. 2001 May 18;84(10):1405-11. doi: 10.1054/bjoc.2001.1776.
• [6] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [7] Clocortolone pivalate: a paired comparison clinical trial of a new topical steroid in eczema/atopic dermatitis. Cutis. 1980 Jan;25(1):96-8.
• [8] Utilization of epidermal phospholipase A2 inhibition to monitor topical steroid action. Br J Dermatol. 1984 Jul;111 Suppl 27:195-203.
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• [10] 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.
• [11] 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.
• [12] 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.
• [13] Phospholipase A2, group IVA (cytosolic, calcium-dependent) (PLA2G4A). SciBX 1(41); doi:10.1038/scibx.2008.999. Nov. 13 2008
• [14] 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.
• [15] Varespladib in the Treatment of Snakebite Envenoming: Development History and Preclinical Evidence Supporting Advancement to Clinical Trials in Patients Bitten by Venomous Snakes. Toxins (Basel). 2022 Nov 11;14(11):783.
• [16] Characteristics of P388/VMDRC.04, a simple, sensitive model for studying P-glycoprotein antagonists. Cancer Res. 1994 Feb 1;54(3):730-7.
• [17] Michaelis-Menten kinetic analysis of drugs of abuse to estimate their affinity to human P-glycoprotein. Toxicol Lett. 2013 Feb 27;217(2):137-42. doi: 10.1016/j.toxlet.2012.12.012. Epub 2012 Dec 27.
• [18] Editor's Highlight: PlacentalDisposition and Effects of Crizotinib: An Ex Vivo Study in the Isolated Dual-Side Perfused Human Cotyledon. Toxicol Sci. 2017 Jun 1;157(2):500-509. doi: 10.1093/toxsci/kfx063.
• [19] Functional evaluation of polymorphisms in the human ABCB1 gene and the impact on clinical responses of antiepileptic drugs. Pharmacogenet Genomics. 2008 May;18(5):390-402. doi: 10.1097/FPC.0b013e3282f85e36.
• [20] Cepharanthine potently enhances the sensitivity of anticancer agents in K562 cells. Cancer Sci. 2005 Jun;96(6):372-6. doi: 10.1111/j.1349-7006.2005.00057.x.
• [21] Clinical pharmacokinetic monitoring of itraconazole is warranted in only a subset of patients. Ther Drug Monit. 2005 Jun;27(3):322-33. doi: 10.1097/01.ftd.0000150135.22645.ea.
• [22] Evaluation of antipsychotic drugs as inhibitors of multidrug resistance transporter P-glycoprotein. Psychopharmacology (Berl). 2006 Sep;187(4):415-23. doi: 10.1007/s00213-006-0437-9. Epub 2006 Jun 30.
• [23] Actions of the selective protein kinase C inhibitor PKC412 on B-chronic lymphocytic leukemia cells in vitro. Haematologica. 2002 Feb;87(2):167-76.
• [24] Characterization of the ATPase activity of the Mr 170,000 to 180,000 membrane glycoprotein (P-glycoprotein) associated with multidrug resistance in K562/ADM cells. Cancer Res. 1988 Sep 1;48(17):4926-32.