Drug Information

Drug (ID: DG00661) and It's Reported Resistant Information

• Name: Miltefosine
• Synonyms: Miltefosine; 58066-85-6; Hexadecylphosphocholine; Miltex; Impavido; Hexadecylphosphorylcholine; HDPC; n-Hexadecylphosphorylcholine; Miltefosinum; Miltefosina; 1-Hexadecylphosphorylcholine; hexadecyl 2-(trimethylammonio)ethyl phosphate; hexadecyl phosphocholine; Miltefosin C; n-hexadecylphosphocholine; hexadecyl 2-(trimethylazaniumyl)ethyl phosphate; D-18506; miltefosin; C21H46NO4P; UNII-53EY29W7EC; NSC605583; hexadecyl (2-(trimethylAmmonio)ethyl) phosphate; monohexadecylphosphocholine; CHEMBL125; monohexadecylphosphorylcholine; HePC;Hexadecyl phosphocholine; 53EY29W7EC; CHEBI:75283; MFCD00133396; MMV688990; NSC-605583; NSC-758968; NCGC00095169-01; Miltefos; DSSTox_CID_25942; DSSTox_RID_81240; DSSTox_GSID_45942; Miltefosinum [INN-Latin]; Miltefosina [INN-Spanish]; Miltefosine [INN:BAN]; Fos-choline 16; Miltefosine (INN); CAS-58066-85-6; D 18506; Choline hexadecyl phosphate; BRN 3690495; Miltextrade mark; HePC Hydrate; Impavidotrade mark; D18506; Impavido (TN); Choline, inner salt; TF-002; 2-(((Hexadecyloxy)hydroxyphosphinyl)oxy)-N,N,N-trimethylethanaminium hydroxide, inner salt; NSC 605583; Choline hydroxide, hexadecyl hydrogen phosphate, inner salt; Choline phosphate, hexadecyl ester, hydroxide, inner salt (6CI); Hexadecyl Phosphorylcholine; H-1850; M-7200; Ethanaminium, 2-(((hexadecyloxy)hydroxyphosphinyl)oxy)-N,N,N-trimethyl-, hydroxide, inner salt; SCHEMBL26215; 4-04-00-01460 (Beilstein Handbook Reference); SPECTRUM1505329; DTXSID7045942; GTPL11355; Hexadecyl Phosphorylcholine Hydrate; HMS1922D16; HMS2089J15; HMS3649I09; Pharmakon1600-01505329; hexadecylphosphocholine, miltefosine; BCP04506; miltefosine (hexadecylphosphocholine); Tox21_111466; BDBM50034220; CCG-35584; CCG-36097; CCG-40025; DL-131; Hexadecyl 2-(trimethyl-.lambda.~5~-azanyl)ethyl hydrogen phosphate; NSC758968; s3056; 1-N-HEXADECYLPHOSPHORYLCHOLINE; AKOS015914886; Tox21_111466_1; BCP9000927; DB09031; NCGC00095169-02; NCGC00095169-03; NCGC00095169-05; NCGC00095169-07; HY-13685; BCP0726000071; FT-0608148; M2445; hexadecyloxy-2-trimethylammonioethylphosphorate; D02494; AB00642217-03; AB00642217_04; Miltefosine, >=98% (perchloric acid titration); A831718; Q411787; Hexadecyl 2-(Trimethylammonio)ethyl Phosphate Hydrate; 2-[hexadecoxy(hydroxy)phosphoryl]oxyethyl-trimethyl-ammonium; Phosphoric Acid Hexadecyl 2-(Trimethylammonio)ethyl Ester; [2-(Hexadecyloxy-hydroxy-phosphoryloxy)-ethyl]-trimethyl-ammonium; 3, 4-hydroxy-N,N,N-trimethyl-, hydroxide, inner salt, 4-oxide; hexadecyl 2-(trimethyl-lambda~5~-azanyl)ethyl hydrogen phosphate; Phosphoric Acid Hexadecyl 2-(Trimethylammonio)ethyl Ester Hydrate; 2-(((Hexadecyloxy)hydroxyphosphinyl)oxy)-N,N,N-trimethylethanaminium hydroxide
• Indication:
  In total 2 Indication(s)
  Leishmaniasis [ICD-11: 1F54]; Approved; [1]
  Visceral leishmaniasis [ICD-11: 1F54]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Leishmaniasis [ICD-11: 1F54]; [2]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Leishmaniasis [ICD-11: 1F54]; [1]
• Target: Phospholipase A2 (PLA2G1B); PA21B_HUMAN; [1]
• Formula: C21H46NO4P
• IsoSMILES: CCCCCCCCCCCCCCCCOP(=O)([O-])OCC[N+](C)(C)C
• InChI: 1S/C21H46NO4P/c1-5-6-7-8-9-10-11-12-13-14-15-16-17-18-20-25-27(23,24)26-21-19-22(2,3)4/h5-21H2,1-4H3
• InChIKey: PQLXHQMOHUQAKB-UHFFFAOYSA-N
• PubChem CID: 3599
• ChEBI ID: CHEBI:75283
• TTD Drug ID: D00FGR
• INTEDE ID: DR1092
• DrugBank ID: DB09031

Type(s) of Resistant Mechanism of This Drug

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Leishmaniasis [ICD-11: 1F54]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 3 (ABCB4) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Leishmaniasis [ICD-11: 1F54.1]
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: In addition, the overexpression of ABC transporters ABCB4(MDR1), ABCG4, and ABCG6 has also been described to be associated with an increased resistance to several alkyl-lysophospholipids analogues, including MIL in Leishmania, due to a reduced intracellular accumulation because of increased efflux of the drug across the plasma membrane.

Key Molecule: ATP binding cassette subfamily G member 4 (ABCG4) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Leishmaniasis [ICD-11: 1F54.1]
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: In addition, the overexpression of ABC transporters ABCB4(MDR1), ABCG4, and ABCG6 has also been described to be associated with an increased resistance to several alkyl-lysophospholipids analogues, including MIL in Leishmania, due to a reduced intracellular accumulation because of increased efflux of the drug across the plasma membrane.

Key Molecule: ABC transporter G family member 6 (ABCG6) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Leishmaniasis [ICD-11: 1F54.1]
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: In addition, the overexpression of ABC transporters ABCB4(MDR1), ABCG4, and ABCG6 has also been described to be associated with an increased resistance to several alkyl-lysophospholipids analogues, including MIL in Leishmania, due to a reduced intracellular accumulation because of increased efflux of the drug across the plasma membrane.

Key Molecule: Multidrug resistance protein 1 (ABCB1) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Leishmaniasis [ICD-11: 1F54.1]
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: In addition, the overexpression of ABC transporters ABCB4(MDR1), ABCG4, and ABCG6 has also been described to be associated with an increased resistance to several alkyl-lysophospholipids analogues, including MIL in Leishmania, due to a reduced intracellular accumulation because of increased efflux of the drug across the plasma membrane.

Key Molecule: Leishmania miltefosine transporter (LMT) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Leishmaniasis [ICD-11: 1F54.1]
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: The uptake of MIL and other alkyl-glycerophospholipids in Leishmania requires a translocation machinery that includes a P-type ATPase named the Leishmania miltefosine transporter (LMT), which is responsible for the translocation of phospholipids from the exoplasmic to the cytoplasmic leaflet of the plasma membrane of Leishmania. The function of LMT depends on its binding to a specific B subunit of LMT called LRos3, which belongs to the CDC50/LEM3 protein family. Both proteins are mutually dependent for their function and their localization at the plasma membrane of Leishmania, being required for MIL uptake and susceptibility.

Key Molecule: Miltefosine transporter beta subunit (ROS3) [1]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Leishmaniasis [ICD-11: 1F54.1]
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: The uptake of MIL and other alkyl-glycerophospholipids in Leishmania requires a translocation machinery that includes a P-type ATPase named the Leishmania miltefosine transporter (LMT), which is responsible for the translocation of phospholipids from the exoplasmic to the cytoplasmic leaflet of the plasma membrane of Leishmania. The function of LMT depends on its binding to a specific B subunit of LMT called LRos3, which belongs to the CDC50/LEM3 protein family. Both proteins are mutually dependent for their function and their localization at the plasma membrane of Leishmania, being required for MIL uptake and susceptibility.

References

• Ref 1: Drug resistance and treatment failure in leishmaniasis: A 21st century challenge .PLoS Negl Trop Dis. 2017 Dec 14;11(12):e0006052. doi: 10.1371/journal.pntd.0006052. eCollection 2017 Dec. 10.1371/journal.pntd.0006052
• Ref 2: Leishmaniasis and various immunotherapeutic approaches .Parasitology. 2018 Apr;145(4):497-507. doi: 10.1017/S003118201600216X. Epub 2016 Dec 15. 10.1017/S003118201600216X