Drug Details

General Information of the Drug (ID: DR2176)
Name
Cyclophosphamide
Synonyms
ASTA; Ciclofosfamida; Ciclophosphamide; Clafen; Claphene; Cycloblastin; Cyclophosphamid; Cyclophosphamides; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclophosphoramide; Cyclostin; Cyklofosfamid; Cytophosphan; Cytophosphane; Cytoxan; Endoxan; Endoxana; Endoxanal; Endoxane; Enduxan; Genoxal; Mitoxan; Neosar; Procytox; Revimmune; Semdoxan; Sendoxan; Senduxan; Zyklophosphamid; Ciclophosphamide [INN]; Cyclophosphamide Sterile; Cyclophosphamide anhydrous; Cyklofosfamid [Czech]; Cytoxan Lyoph; Endoxan R; Lyophilized Cytoxan; Zyklophosphamid [German]; ASTA B518; Asta B 518; B 518; C 0768; CB 4564; SK 20501; B-518; CB-4564; Ciclofosfamida [INN-Spanish]; Cyclophosphamide (INN); Cyclophosphamide (TN); Cyclophosphamide (anhydrous form); Cyclophosphamide (anhydrous); Cyclophosphamidum [INN-Latin]; Cytoxan (TN); Endoxan (TN); Endoxan-Asta; Neosar (TN); Occupation, cyclophosphamide exposure; Procytox (TN); Revimmune (TN); Bis(2-Chloroethyl)phosphami de cyclic propanolamide; Bis(2-Chloroethyl)phosphamide cyclic propanolamide ester; Bis(2-chloroethyl)phosphoramide cyclic propanolamide ester; D,L-Cyclophosphamide; Cyclophosphamide, (+-)-Isomer; N,N-Bis(2-chloroethyl)-1,3,2-oxazaphosphinan-2-amine 2-oxide; (+-)-Cyclophosphamide; (-)-Cyclophosphamide; (RS)-Cyclophosphamide; 1-(bis(2-chloroethyl)amino)-1-oxo-2-aza-5-oxaphosphoridine; 1-Bis(2-chloroethyl)amino-1-oxo-2-aza-5-oxaphosphoridin; 4-Hydroxy-cyclophosphan-mamophosphatide
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Molecular Type
Small molecule
Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z] Approved [1]
Structure
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2D MOL

3D MOL

ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 1 h
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability
Bioavailability
74% of drug becomes completely available to its intended biological destination(s)
Clearance
The drug present in the plasma can be removed from the body at the rate of 1.1 mL/min/kg
Elimination
6.5% of drug is excreted from urine in the unchanged form
Half-life
The concentration or amount of drug in body reduced by one-half in 3 - 12 hours
Metabolism
The drug is metabolized via the liver
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 19.15051 micromolar/kg/day
Unbound Fraction
The unbound fraction of drug in plasma is 0.87%
Vd
The volume of distribution (Vd) of drug is 30-50 L
Water Solubility
The ability of drug to dissolve in water is measured as 40 mg/mL
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Formula
C7H15Cl2N2O2P
PubChem CID
2907
Canonical SMILES
C1CNP(=O)(OC1)N(CCCl)CCCl
InChI
1S/C7H15Cl2N2O2P/c8-2-5-11(6-3-9)14(12)10-4-1-7-13-14/h1-7H2,(H,10,12)
InChIKey
CMSMOCZEIVJLDB-UHFFFAOYSA-N
CAS Number
CAS 50-18-0
GDSC
Cyclophosphamide
TTD Drug ID
D0CT9C
DrugBank ID
DB00531
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Enhance the Efficacy of This Drug
          Abrin      Abrus precatorius     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model Mice bearing intramuscularly growing Lewis lung carcinoma were used as animal model in this study.
                    Experimental
                    Result(s)		 Small to moderate doses of abrin significantly potentiated the therapeutic effect of cyclophosphamide without increasing the toxicity.
          Fisetin      Toxicodendron succedaneum     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression PECAM1  Molecule Info 
Pathway MAP
                    In-vitro Model EA.hy 926 CVCL_3901 Healthy Homo sapiens
3LL CVCL_5653 Malignant tumors Mus musculus
NIH 3T3 CVCL_0594 Healthy Mus musculus
                    In-vivo Model Aliquots of cells (0.1 ml, 3 * 106 cells) were mixed with 0.2 ml of phenol red-free Matrigel and injected into the right flank of mice.
                    Experimental
                    Result(s)		 Fisetin not only displays in vitro and in vivo antiangiogenic properties, but also can markedly improve the in vivo antitumour effect of CPA.
          Ginsenoside      Panax ginseng     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model C57BL/6 mice were inoculated by subcutaneous injection in the right front axilla with 1 * 106 Lewis cells.
                    Experimental
                    Result(s)		 Combination of Ginsenoside H dripping pills and cyclophosphamide improve paraneoplastic syndrome and inhibit postoperative recurrence via the reversion of Th1/Th2 shift.
          Ginsenoside Rg3      Panax ginseng     Click to Show/Hide the Molecular Data of This NP
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model Lewis lung carcinoma (1*106/0.1 mL) was inoculated subcutaneously in the right flank of each C57/BL6 mouse.
                    Experimental
                    Result(s)		 Continuous low-dose regimen of CTX increases the efficacy of targeting the tumor microvasculature, which produces therapeutic activity with decreased toxicity.
          Polysaccharide      Ophiocordyceps sinensis     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression CD178  Molecule Info 
Pathway MAP
Up-regulation Expression FAS  Molecule Info 
Pathway MAP
                    In-vitro Model H22 CVCL_H613 Hepatocellular carcinoma of the mouse Mus musculus
                    In-vivo Model H22 cells suspension (1 * 107 cell/mL) with sterile normal saline was subcutaneously inoculated into the right oxter of forty-eight healthy mice at a dose of 0.2 mL per mice.
                    Experimental
                    Result(s)		 Combination treatment with LEP-2a and CTX processed a significantly synergistic anti-tumor effect in H22 tumor-bearing mice through Fas/FasL mediated caspase-dependent death pathway and mitochondria apoptosis pathway.
          Roxithromycin      Escherichia coli     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression ABCB1  Molecule Info 
Pathway MAP
                    In-vitro Model P388 CVCL_7222 Mouse lymphoma Mus musculus
                    Experimental
                    Result(s)		 The combination cyclophosphamide and roxithromycin, but not the individual compounds, is toxic to endothelial cells by inducing apoptosis.
          Thymoquinone      Nigella sativa     Click to Show/Hide the Molecular Data of This NP
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Down-regulation Expression AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression FASN  Molecule Info 
Pathway MAP
Down-regulation Expression HER2  Molecule Info 
Pathway MAP
Down-regulation Expression PTEN  Molecule Info 
Pathway MAP
                    In-vitro Model SK-BR-3 CVCL_0033 Breast adenocarcinoma Homo sapiens
MDA-231 Breast cancer Homo sapiens
                    Experimental
                    Result(s)		 TQ can broadly augment the effect of cyclo in breast cancer cases irrespective of Her-2+ or Her-.
    β. A List of Natural Product(s) Able to Decrease the Adverse Effect of This Drug
          Apocynin      Picrorhiza kurrooa     Click to Show/Hide the Molecular Data of This NP
                 Decreasing Adverse Drug Reaction     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Molecule(s)
                    Regulation		 Up-regulation Expression AKT1  Molecule Info 
Pathway MAP
Up-regulation Expression GABPA  Molecule Info 
Pathway MAP
Up-regulation Expression GCLC  Molecule Info 
Pathway MAP
Up-regulation Expression HMOX1  Molecule Info 
Pathway MAP
Down-regulation Expression KEAP1  Molecule Info 
Pathway MAP
Up-regulation Expression mTOR  Molecule Info 
Pathway MAP
Up-regulation Expression PIK3CB  Molecule Info 
Pathway MAP
Up-regulation Expression SOD3  Molecule Info 
Pathway MAP
                    In-vivo Model Male Wistar rats weighing 180-210 g were used in this study.
                    Experimental
                    Result(s)		 Acetovanillone prevents cyclophosphamide-induced acute lung injury by modulating PI3K/Akt/mTOR and Nrf2 signaling in rats.
Target and Pathway
Target(s) Human Deoxyribonucleic acid (hDNA)  Molecule Info  [10]
References
Reference 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: 7154).
Reference 2 Treatment of micrometastases from Lewis lung carcinoma with abrin and cyclophosphamide, given singly and in combination. Int J Cancer. 1979 Apr 15;23(4):530-5.
Reference 3 Improved antiangiogenic and antitumour activity of the combination of the natural flavonoid fisetin and cyclophosphamide in Lewis lung carcinoma-bearing mice. Cancer Chemother Pharmacol. 2011 Aug;68(2):445-55.
Reference 4 Combination of Ginsenoside H dripping pills and cyclophosphamide improve paraneoplastic syndrome and inhibit postoperative recurrence via the reversion of Th1/Th2 shift. Biomed Pharmacother. 2018 Dec;108:865-875.
Reference 5 Antiangiogenic effect of low-dose cyclophosphamide combined with ginsenoside Rg3 on Lewis lung carcinoma. Biochem Biophys Res Commun. 2006 Apr 14;342(3):824-8.
Reference 6 Synergistic antitumor effect of polysaccharide from Lachnum sp. in combination with cyclophosphamide in hepatocellular carcinoma. Carbohydr Polym. 2018 Sep 15;196:33-46.
Reference 7 Mechanisms of venoocclusive disease resulting from the combination of cyclophosphamide and roxithromycin. Ther Drug Monit. 2006 Dec;28(6):766-74.
Reference 8 Thymoquinone Augments Cyclophosphamide-Mediated Inhibition of Cell Proliferation in Breast Cancer Cells. Asian Pac J Cancer Prev. 2019 Apr 29;20(4):1153-1160.
Reference 9 Acetovanillone prevents cyclophosphamide-induced acute lung injury by modulating PI3K/Akt/mTOR and Nrf2 signaling in rats. Phytother Res. 2021 May 9.
Reference 10 O6-methylguanine-DNA methyltransferase activity and sensitivity to cyclophosphamide and cisplatin in human lung tumor xenografts. Int J Cancer. 1998 Sep 11;77(6):919-22.
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