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Drug-Target Interaction

Drug

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PubChem ID:2907
Structure:
Synonyms:
(+)-cyclophosphamide
(+)-n,n-bis(2-chloroethyl)tetrahydro-2h-1,3,2-oxazaphosphorin-2-amine 2-oxide
(+-)-Cyclophosphamide
(+-)-N,N-Bis(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide
(-)-Cyclophosphamide
(Bis(chloro-2-ethyl)amino)-2-tetrahydro-3,4,5,6-oxazaphosphorine-1,3,2-oxide-2 hydrate
(RS)-Cyclophosphamide
1-(bis(2-chloroethyl)amino)-1-oxo-2-aza-5-oxaphosphoridine
1-Bis(2-chloroethyl)amino-1-oxo-2-aza-5-oxaphosphoridin
2-(bis(2-Chloroethyl)-amino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide
2-(Bis(2-chloroethyl)amino)-2H-1,3,2-oxazaphosphorine 2-oxide
2-(Bis(2-chloroethyl)amino)tetrahydro-2H-1,3,2-oxazophosphorine 2-oxide
2-(di(2-chloroethyl)amino)-1-oxa-3-aza-2-phosphacyclohexane 2-oxide
2-[Bis(2-chloroethyl)amino]-2H-1,3,2-oxazaphosphorine 2-oxide
2-[Bis(2-chloroethylamino)]-tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide
2H-1,3,2-Oxazaphosphorin-2-amine, N,N-bis(2-chloroethyl)tetrahydro-,
2H-1,3,2-Oxazaphosphorin-2-amine, N,N-bis(2-chloroethyl)tetrahydro-, 2-oxide
2H-1,3,2-Oxazaphosphorin-2-amine, N,N-bis(2-chloroethyl)tetrahydro-, 2-oxide (9CI)
2h-1,3,2-oxazaphosphorin-2-amine, n,n-bis(2-chloroethyl)tetrahydro-, 2-oxide, ()-
2H-1,3,2-Oxazaphosphorin-2-amine, N,N-bis(2-chloroethyl)tetrahydro-, 2-oxide, (+)-
2H-1,3,2-Oxazaphosphorin-2-amine, N,N-bis(2-chloroethyl)tetrahydro-, 2-oxide, (+-)-
2H-1,3,2-Oxazaphosphorin-2-amine, N,N-bis(2-chloroethyl)tetrahydro-, 2-oxide, (-)-
2H-1,3,2-Oxazaphosphorine, 2-(bis(2-chloroethyl)amino)tetrahydro-, 2-oxide
2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide
2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
4-27-00-09750 (Beilstein Handbook Reference)
4-Hydroxy-cyclophosphan-mamophosphatide
50-18-0
60007-95-6
6055-19-2
75526-90-8
AI3-26198
AIDS-002314
AIDS002314
ASTA
Asta B 518
ASTA B518
B 518
B-518
bis(2-Chloroethyl)phosphami de cyclic propanolamide
bis(2-Chloroethyl)phosphamide cyclic propanolamide ester
Bis(2-chloroethyl)phosphoramide cyclic propanolamide ester
BRN 0011744
BSPBio_002099
C07888
C7H15Cl2N2O2P
CB 4564
CB-4564
CCRIS 188
CHEBI:4027
Ciclofosfamida [INN-Spanish]
Ciclophosphamide
Ciclophosphamide [INN]
Clafen
Claphene
CP
CPA
CTX
CY
Cycloblastin
Cyclophosphamid
Cyclophosphamide
Cyclophosphamide (anhydrous form)
Cyclophosphamide (anhydrous)
Cyclophosphamide (INN)
Cyclophosphamide (TN)
Cyclophosphamide anhydrous
Cyclophosphamide monohydrate
Cyclophosphamide, (+-)-Isomer
Cyclophosphamides
Cyclophosphamidum
Cyclophosphamidum [INN-Latin]
Cyclophosphan
Cyclophosphane
Cyclophosphanum
Cyclophosphoramide
Cyclostin
Cyklofosfamid
Cyklofosfamid [Czech]
Cytophosphan
Cytophosphane
Cytoxan
Cytoxan (TN)
D,L-Cyclophosphamide
D07760
DB00531
DivK1c_000246
EINECS 200-015-4
Endoxan
Endoxan R
Endoxan-Asta
Endoxana
Endoxanal
Endoxane
Enduxan
EU-0100238
Genoxal
Hexadrin
HSDB 3047
IDI1_000246
KBio1_000246
KBio2_001338
KBio2_003906
KBio2_006474
KBio3_001319
KBioGR_000888
KBioSS_001338
Lopac-C-0768
Lopac0_000238
LS-1302
LS-99787
Lyophilized Cytoxan
Mitoxan
N,N-Bis(.beta.-chloroethyl)-N',O-propylenephosphoric acid ester amide monohydrate
N,N-Bis(.beta.-chloroethyl)-N',O-trimethylenephosphoric acid ester diamide
N,N-bis(2-chloroethyl)-1,3,2-oxazaphosphinan-2-amine 2-oxide
N,N-bis(2-chloroethyl)-2-oxo-1-oxa-3-aza-2$l^{5}-phosphacyclohexan-2-amine
N,N-Bis(2-chloroethyl)-N',O-propylenephosphoric acid ester diamide
N,N-bis(2-chloroethyl)-N'-(3-h ydroxypropyl)phosphorodiamidic acid intramol. ester
N,N-bis(2-chloroethyl)-N'-(3-hydroxypropyl)phosphorodiamidic acid intramol. ester
N,N-Bis(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide
N,N-Bis(2-Chloroethyl)tetrahydro-2H-1,3,2-Oxazaphosphorin-2-Amine, 2-Oxide
N,N-Bis(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine-2-oxide
N,N-Bis(beta-chloroethyl)-N',O-propylenephosphoric acid ester diamide
N,N-Bis(beta-chloroethyl)-N',O-trimethylenephosphoric acid ester diamide
N,N-Bis-(.beta.-chloraethyl)-N',O-propylen-phosphorsaeure-ester-diamid
N,N-Bis-(beta-chloraethyl)-N',O-propylen-phosphorsaeure-ester-diamid [German]
N,N-Di(2-chloroethyl)-N,O-propylene-phosphoric acid ester diamide
N-bis(beta-Chloroethyl)-N'O,trimethylenephos phoric acid ester diamide
N-bis(beta-Chloroethyl)-N'O,trimethylenephosphoric acid ester diamide
NCGC00015209-01
NCGC00091741-02
NCGC00091741-03
NCGC00091741-04
NCI-C04900
NCI60_002097
Neosar
NINDS_000246
NSC 26271
NSC-26271
NSC26271
NSC273033
NSC273034
Occupation, cyclophosphamide exposure
Phosphorodiamidic acid, N,N-bis(2-chloroethyl)-N'-(3-hydroxypropyl)-, intramol. ester
Procytox
RCRA waste no. U058
RCRA waste number U058
Semdoxan
Sendoxan
Senduxan
SK 20501
SPBio_001071
Spectrum2_001146
Spectrum3_000370
Spectrum4_000304
Spectrum5_000795
Spectrum_000858
STK177249
tatrahydro-2-(Bis(2-chloroethyl)amino)-2H-1,3,2-oxazaphosphorine 2-oxide
te trahydro-N,N-bis(2-chloroethyl)-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide
tetrahydro-N,N-bis(2-chloroethyl)-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide
WLN: T6MPOTJ BO BN2G2G
Zyklophosphamid
Zyklophosphamid [German]
[Bis(chloro-2-ethyl)amino]-2-tetrahydro-3,4,5,6-oxazaphosphorine-1,3,2-oxide-2 hydrate
ATC-Codes:
Side-Effects:
Side-EffectFrequency
anaphylactic reaction0.0010
malaise0.0010
interstitial pneumonia0.0010
thrombocytopenia0.0010
pulmonary fibrosis0.0010
pneumonitis0.0010
pericarditis0.0010
myocarditis0.0010
leukopenia0.0010
infection0.0010
syndrome of inappropriate antidiuretic hormone0.0010
anemia0.0010
asthenia0.0010
diabetes mellitus0.0010
dizziness0.0010
fever0.0010
headache0.0010
congestive heart failure0.0010
acute renal failure0
urinary frequency0
heart disease0
swelling0
tachycardia0
dermatitis0
sweating0
electrolyte imbalance0
myopia0
pruritus0
ulcer0
jaundice0
weakness0
cardiomyopathy0
agitation0
hematuria0
heart failure0
stomatitis0
sterility0
sneezing0
hyperkalemia0
hemorrhage0
neutropenia0
lupus0
renal failure0
dyspnea0
vomiting0
rhabdomyolysis0
hepatic encephalopathy0
amenorrhea0
nasal congestion0
dermatomyositis0
pancytopenia0
colitis0
anorexia0
sinus congestion0
acute pancreatitis0
toxic epidermal necrolysis0
constitutional symptoms0
lymphocytic leukemia0
rash0
nausea0
recurrent urinary tract infections0
alopecia0
hyponatremia0
flushing0
hyperpigmentation0
ascites0
constipation0
pain0
arrhythmia0
erythema0
bilirubinemia0
myocardial infarction0
confusion0
stevens - johnson syndrome0
hyperuricemia0
urticaria0
aplastic anemia0
cardiac tamponade0
blurred vision0
fibrosis0
hepatomegaly0
ureteral obstruction0
viral infection0
shock0
bacterial infections0
cystitis0
weight gain0
spasm0
dysuria0
cough0
hypersensitivity0
myxedema0
hyperglycemia0
edema0
fatigue0
rhinorrhea0
diarrhea0
methemoglobinemia0

Target

show target details
Uniprot ID:CP2C9_HUMAN
Synonyms:
(R)-limonene 6-monooxygenase
(S)-limonene 6-monooxygenase
(S)-limonene 7-monooxygenase
CYPIIC9
Cytochrome P450 2C9
P-450MP
P450 MP-4/MP-8
P450 PB-1
S-mephenytoin 4-hydroxylase
EC-Numbers:1.14.13.48
1.14.13.49
1.14.13.80
Organism:Homo sapiens
Human
PDB IDs:1OG2 1OG5 1R9O
Structure:
1R9O

Binding Affinities:

Ki: Kd:Ic 50:Ec50/Ic50:
----
----
----
----

References:

12739762
16475710
8242617
Differential activation of cyclophosphamide and ifosphamide by cytochromes P-450 2B and 3A in human liver microsomes.. T K Chang; G F Weber; C L Crespi; D J Waxman (1993) Cancer research display abstract
The present study identifies the specific human cytochrome P-450 (CYP) enzymes involved in hydroxylation leading to activation of the anticancer drug cyclophosphamide and its isomeric analogue, ifosphamide. Substantial interindividual variation (4-9-fold) was observed in the hydroxylation of these oxazaphosphorines by a panel of 12 human liver microsomes, and a significant correlation was obtained between these 2 activities (r = 0.85, P < 0.001). Enzyme kinetic analyses revealed that human liver microsomal cyclophosphamide 4-hydroxylation and ifosphamide 4-hydroxylation are best described by a 2-component Michaelis-Menten model composed of both low Km and high Km P-450 4-hydroxylases. To ascertain whether one or more human P-450 enzymes are catalytically competent in activating these oxazaphosphorines, microsomal fractions prepared from a panel of human B-lymphoblastoid cell lines stably transformed with individual P-450 complementary DNAs were assayed in vitro for oxazaphosphorine activation. Expressed CYP2A6, -2B6, -2C8, -2C9, and -3A4 were catalytically competent in hydroxylating cyclophosphamide and ifosphamide. Whereas CYP2C8 and CYP2C9 have the characteristics of low Km oxazaphosphorine 4-hydroxylases, CYP2A6, -2B6, and -3A4 are high Km forms. In contrast, CYP1A1, -1A2, -2D6, and -2E1 did not produce detectable activities. Furthermore, growth of cultured CYP2A6- and CYP2B6-expressing B-lymphoblastoid cells, but not of CYP-negative control cells, was inhibited by cyclophosphamide and ifosphamide as a consequence of prodrug activation to cytotoxic metabolites. Experiments with P-450 form-selective chemical inhibitors and inhibitory anti-P-450 antibodies were then performed to determine the contributions of individual P-450s to the activation of these drugs in human liver microsomes. Orphenadrine (a CYP2B6 inhibitor) and anti-CYP2B IgG inhibited microsomal cyclophosphamide hydroxylation to a greater extent than ifosphamide hydroxylation, consistent with the 8-fold higher activity of complementary DNA-expressed CYP2B6 with cyclophosphamide. In contrast, troleandomycin, a selective inhibitor of CYP3A3 and -3A4, and anti-CYP3A IgG substantially inhibited microsomal ifosphamide hydroxylation but had little or no effect on microsomal cyclophosphamide hydroxylation. By contrast, the CYP2D6-selective inhibitor quinidine did not affect either microsomal activity, while anti-CYP2A antibodies had only a modest inhibitory effect. Overall, the present study establishes that liver microsomal CYP2B and CYP3A preferentially catalyze cyclophosphamide and ifosphamide 4-hydroxylation, respectively, suggesting that liver P-450-inducing agents targeted at these enzymes might be used in cancer patients to enhance drug activation and therapeutic efficacy.
9157990