4-Hydroxyifosfamide (BioDeep_00000011261)

 

Secondary id: BioDeep_00001876857

human metabolite Endogenous blood metabolite Chemicals and Drugs


代谢物信息卡片


3-(2-chloroethyl)-2-[(2-chloroethyl)amino]-4-hydroxy-1,3,2λ⁵-oxazaphosphinan-2-one

化学式: C7H15Cl2N2O3P (276.0197)
中文名称:
谱图信息: 最多检出来源 Macaca mulatta(otcml) 17.11%

分子结构信息

SMILES: C1COP(=O)(N(C1O)CCCl)NCCCl
InChI: InChI=1S/C7H15Cl2N2O3P/c8-2-4-10-15(13)11(5-3-9)7(12)1-6-14-15/h7,12H,1-6H2,(H,10,13)

描述信息

4-Hydroxyifosfamide is the active metabolite of the bifunctional alkylating cytostatic drug known as ifosfamide. 4-Hydroxyifosfamide is a member of the compound class known as oxazaphosphorines. Oxazaphosphorines are any saturated six-membered heterocycle containing three carbon atoms and one each of oxygen, nitrogen and phosphorus, especially one in which the phosphorus atom is linked to both the nitrogen and oxygen atoms. 4-Hydroxyifosfamide is very unstable in plasma and a stabilization procedure by adding citric acid has been developed (PMID: 9172103). 4-Hydroxyifosfamide is known to pass through the blood-brain barrier, and can reach cerebrospinal fluid concentrations that are almost as high as plasma concentrations (PMID: 9677448). 4-Hydroxyifosfamide is only found in individuals who have consumed or received the drug Ifosfamide.
D000970 - Antineoplastic Agents > D018906 - Antineoplastic Agents, Alkylating > D009588 - Nitrogen Mustard Compounds
D000970 - Antineoplastic Agents > D018906 - Antineoplastic Agents, Alkylating > D010752 - Phosphoramide Mustards

同义名列表

4 个代谢物同义名

3-(2-chloroethyl)-2-[(2-chloroethyl)amino]-4-hydroxy-1,3,2λ⁵-oxazaphosphinan-2-one; 3-(2-Chloroethyl)-2-((2-chloroethyl)amino)-1,3,2-oxazaphosphinan-4-ol 2-oxide; 4-Hydroxy-ifosfamide; 4-Hydroxyifosfamide



数据库引用编号

12 个数据库交叉引用编号

分类词条

相关代谢途径

Reactome(0)

BioCyc(0)

PlantCyc(0)

代谢反应

2 个相关的代谢反应过程信息。

Reactome(0)

BioCyc(0)

WikiPathways(0)

Plant Reactome(0)

INOH(0)

PlantCyc(0)

COVID-19 Disease Map(0)

PathBank(2)

  • Ifosfamide Action Pathway: Ifosfamide + Oxygen + Water ⟶ 2-Dechloroethylifosfamide + 3-Dechloroethylifosfamide + Chloroacetaldehyde + Hydrogen peroxide
  • Ifosfamide Metabolism Pathway: Ifosfamide + Oxygen + Water ⟶ 2-Dechloroethylifosfamide + 3-Dechloroethylifosfamide + Chloroacetaldehyde + Hydrogen peroxide

PharmGKB(0)

1 个相关的物种来源信息

在这里通过桑基图来展示出与当前的这个代谢物在我们的BioDeep知识库中具有相关联信息的其他代谢物。在这里进行关联的信息来源主要有：

  • PubMed: 来源于PubMed文献库中的文献信息，我们通过自然语言数据挖掘得到的在同一篇文献中被同时提及的相关代谢物列表，这个列表按照代谢物同时出现的文献数量降序排序，取前10个代谢物作为相关研究中关联性很高的代谢物集合展示在桑基图中。
  • NCBI Taxonomy: 通过文献数据挖掘，得到的代谢物物种来源信息关联。这个关联信息同样按照出现的次数降序排序，取前10个代谢物作为高关联度的代谢物集合展示在桑吉图上。
  • Chemical Taxonomy: 在物质分类上处于同一个分类集合中的其他代谢物
  • Chemical Reaction: 在化学反应过程中，存在为当前代谢物相关联的生化反应过程中的反应底物或者反应产物的关联代谢物信息。

点击图上的相关代谢物的名称，可以跳转到相关代谢物的信息页面。

亚细胞结构定位 关联基因列表
Cytoplasm 8 ABCB1, ALB, CYP2B6, CYP3A4, HPGDS, MVP, MX1, TYR
Peripheral membrane protein 2 CYP2B6, MX1
Endoplasmic reticulum membrane 3 CYP2B6, CYP3A4, MX1
Nucleus 5 ALB, DLST, MVP, MX1, MXI1
cytosol 7 ALB, DLST, GCLM, HPGDS, MVP, MX1, MXI1
centrosome 1 ALB
nucleoplasm 4 DLST, HPGDS, MXI1, SLC3A2
RNA polymerase II transcription regulator complex 1 MXI1
Cell membrane 2 ABCB1, SLC3A2
Multi-pass membrane protein 2 ABCB1, ABCC3
Synapse 1 SLC3A2
cell junction 1 SLC3A2
cell surface 2 ABCB1, SLC3A2
Golgi apparatus 1 ALB
lysosomal membrane 1 SLC3A2
Lysosome 1 TYR
plasma membrane 4 ABCB1, ABCC3, IFNLR1, SLC3A2
Membrane 8 ABCB1, ABCC3, CYP3A4, DLST, IFNLR1, MVP, MX1, SLC3A2
apical plasma membrane 2 ABCB1, SLC3A2
basolateral plasma membrane 2 ABCC3, SLC3A2
extracellular exosome 4 ABCB1, ALB, MVP, SLC3A2
Lysosome membrane 1 SLC3A2
endoplasmic reticulum 1 ALB
extracellular space 1 ALB
perinuclear region of cytoplasm 3 MVP, MX1, TYR
mitochondrion 1 DLST
protein-containing complex 1 ALB
intracellular membrane-bounded organelle 4 CYP2B6, CYP3A4, HPGDS, TYR
Microsome membrane 2 CYP2B6, CYP3A4
Single-pass type I membrane protein 2 IFNLR1, TYR
Secreted 1 ALB
extracellular region 2 ALB, MVP
Mitochondrion matrix 1 DLST
mitochondrial matrix 1 DLST
anchoring junction 2 ALB, SLC3A2
nuclear membrane 1 MX1
nucleolus 1 MXI1
Melanosome membrane 1 TYR
Golgi-associated vesicle 1 TYR
Single-pass type II membrane protein 1 SLC3A2
Apical cell membrane 2 ABCB1, SLC3A2
Cytoplasm, perinuclear region 2 MVP, MX1
microtubule 1 MX1
ciliary basal body 1 ALB
chromatin 1 MXI1
cytoskeleton 1 MVP
centriole 1 ALB
spindle pole 1 ALB
blood microparticle 1 ALB
Basolateral cell membrane 2 ABCC3, SLC3A2
Nucleus, nuclear pore complex 1 MVP
nuclear pore 1 MVP
Melanosome 2 SLC3A2, TYR
basal plasma membrane 2 ABCC3, SLC3A2
ficolin-1-rich granule lumen 1 MVP
secretory granule lumen 1 MVP
endoplasmic reticulum lumen 1 ALB
platelet alpha granule lumen 1 ALB
[Isoform 2]: Cytoplasm 1 MX1
oxoglutarate dehydrogenase complex 1 DLST
ribonucleoprotein complex 1 MVP
Basal cell membrane 1 ABCC3
external side of apical plasma membrane 1 ABCB1
oxidoreductase complex 1 DLST
amino acid transport complex 1 SLC3A2
apical pole of neuron 1 SLC3A2
oxoadipate dehydrogenase complex 1 DLST
glutamate-cysteine ligase complex 1 GCLM
ciliary transition fiber 1 ALB
interleukin-28 receptor complex 1 IFNLR1


文献列表

  • Alain Deroussent, Charles Skarbek, Adeline Maury, Hubert Chapuis, Estelle Daudigeos-Dubus, Ludivine Le Dret, Sylvère Durand, Patrick Couvreur, Didier Desmaële, Angelo Paci. Simultaneous quantification of preactivated ifosfamide derivatives and of 4-hydroxyifosfamide by high performance liquid chromatography-tandem mass spectrometry in mouse plasma and its application to a pharmacokinetic study. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. 2015 Jun; 992(?):30-5. doi: 10.1016/j.jchromb.2015.04.025. [PMID: 25939095]
  • Charles Skarbek, Lea L Lesueur, Hubert Chapuis, Alain Deroussent, Catherine Pioche Durieu, Aurore Daville, Joachim Caron, Michael Rivard, Thierry Martens, Jean-Rémi Bertrand, Eric Le Cam, Gilles Vassal, Patrick Couvreur, Didier Desmaele, Angelo Paci. Preactivated oxazaphosphorines designed for isophosphoramide mustard delivery as bulk form or nanoassemblies: synthesis and proof of concept. Journal of medicinal chemistry. 2015 Jan; 58(2):705-17. doi: 10.1021/jm501224x. [PMID: 25494842]
  • Philipp Kiewe, Martin Neumann, Thomas Wagner, Sepp Seyfert, Heike Albrecht, Eckhard Thiel, Agnieszka Korfel. Penetration of ifosfamide and its active metabolite 4-OH-ifosfamide into cerebrospinal fluid of patients with CNS malignancies. Cancer chemotherapy and pharmacology. 2011 Jan; 67(1):27-33. doi: 10.1007/s00280-010-1274-4. [PMID: 20182727]
  • T Kerbusch, R A Mathĵt, H J Keizer, J Ouwerkerk, S Rodenhuis, J H Schellens, J H Beijnen. Population pharmacokinetics and exploratory pharmacodynamics of ifosfamide and metabolites after a 72-h continuous infusion in patients with soft tissue sarcoma. European journal of clinical pharmacology. 2001 Sep; 57(6-7):467-77. doi: 10.1007/s002280100322. [PMID: 11699611]
  • Y Hirano, T Ushiyama, K Suzuki, K Fujita. Clinical application of an in vitro chemosensitivity test, the Histoculture Drug Response Assay, to urological cancers: wide distribution of inhibition rates in bladder cancer and renal cell cancer. Urological research. 1999 Dec; 27(6):483-8. doi: 10.1007/s002400050139. [PMID: 10651138]
  • T Kerbusch, A D Huitema, J J Kettenes-van den Bosch, H J Keizer, J Ouwerkerk, J de Kraker, J H Beijnen. High-performance liquid chromatographic determination of stabilized 4-hydroxyifosfamide in human plasma and erythrocytes. Journal of chromatography. B, Biomedical sciences and applications. 1998 Sep; 716(1-2):275-84. doi: 10.1016/s0378-4347(98)00298-9. [PMID: 9824241]
  • G P Kaijser, J De Kraker, A Bult, W J Underberg, J H Beijnen. Pharmacokinetics of ifosfamide and some metabolites in children. Anticancer research. 1998 May; 18(3B):1941-9. doi: NULL. [PMID: 9677448]
  • S K Brüggemann, J Kisro, T Wagner. Ifosfamide cytotoxicity on human tumor and renal cells: role of chloroacetaldehyde in comparison to 4-hydroxyifosfamide. Cancer research. 1997 Jul; 57(13):2676-80. doi: . [PMID: 9205076]
  • G P Kaijser, P G Ter Riet, J de Kraker, A Bult, J H Beijnen, W J Underberg. Determination of 4-hydroxyifosfamide in biological matrices by high-performance liquid chromatography. Journal of pharmaceutical and biomedical analysis. 1997 Mar; 15(6):773-81. doi: 10.1016/s0731-7085(96)01893-6. [PMID: 9172103]
  • V Kurowski, T Wagner. Urinary excretion of ifosfamide, 4-hydroxyifosfamide, 3- and 2-dechloroethylifosfamide, mesna, and dimesna in patients on fractionated intravenous ifosfamide and concomitant mesna therapy. Cancer chemotherapy and pharmacology. 1997; 39(5):431-9. doi: 10.1007/s002800050594. [PMID: 9054957]
  • R F Struck, D M McCain, S W Tendian, K H Tillery. Quantification of 4-hydroxyifosfamide in plasma of ifosfamide-treated mice. Cancer chemotherapy and pharmacology. 1997; 40(1):57-9. doi: 10.1007/s002800050625. [PMID: 9137530]
  • M Mohrmann, A Pauli, M Ritzer, B Schönfeld, B Seifert, M Brandis. Inhibition of sodium-dependent transport systems in LLC-PK1 cells by metabolites of ifosfamide. Renal physiology and biochemistry. 1992 Nov; 15(6):289-301. doi: 10.1159/000173465. [PMID: 1282722]
  • I Ikeuchi, T Amano. Fluorometric determination of 4-hydroxyifosfamide in blood and urine. Chemical & pharmaceutical bulletin. 1985 Jun; 33(6):2416-20. doi: 10.1248/cpb.33.2416. [PMID: 4064201]
  • K Misiura, A Okruszek, K Pankiewicz, W J Stec, Z Czownicki, B Utracka. Stereospecific synthesis of chiral metabolites of ifosfamide and their determination in the urine. Journal of medicinal chemistry. 1983 May; 26(5):674-9. doi: 10.1021/jm00359a010. [PMID: 6842506]