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The following message was posted to: PharmPK
Hi everybody,
Does anyone know of a specific 2B6 inhibitor? Thanks.
-Saileta
Scientist
ADME-PK
Sunesis Pharmaceuticals
341 Oyster Point Blvd
South San Francisco, CA 94080
Tel.: 650-266-3679
Fax: 650-266-3502
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The following message was posted to: PharmPK
Saileta,
Activity of CYP 2B6 can be inhibited by orphenadrine (it is a mechanism
based inhibitor).
Shakil A. Saghir, M.S.P.H., Ph.D.
Senior Research Toxicologist
The Dow Chemical Co.
1803 Bldg., Midland, MI 48674
Phone: (989) 636-8708, Fax: (989) 638-9863
Email: ssaghir.-a-.dow.com
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The following message was posted to: PharmPK
Try out orphenadrine (500 uM), which is a mechanism based inhibitor.
Jie
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The following message was posted to: PharmPK
Hi Saileta,
Although orphenadrine is used as CYP2B6 inhibitor, it is nonspecific and
mechanism based inhbitor. There was a article published in Drug metab
dispos, which says triethylenethiophospharamide as a specific inhibitor
of CYP2B6.
Reference: Triethylenethiophosphoramide is a specific inhibitor of
cytochrome P450 2B6: implications for cyclophosphamide metabolism, Drug
Metab Dispos. 2002 May;30(5):525-30
Hope this helps
Azher M. Hussain, Ph.D
Post Doctoral Researcher
P450 Inhibition
Xenotech, LLC
Phone: 913 227 7172
Email: ahussain.at.xenotechllc.com
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Saileta,
You can try several antibodies/IgG preparations out in the marketplace
(refer to www.gentest.com) for your in-vitro studies, if you are
interested in that.
-Partha.
Partha Roy, Ph.D.
Forest Research Institute
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Hi,
There is a good paper on CYP2B6 inhibition that you should check:
Rae JM, Soukhova NV, Flockhart DA, Desta Z.
Triethylenethiophosphoramide is a specific inhibitor of cytochrome P450
2B6: implications for cyclophosphamide metabolism.
Drug Metab Dispos. 2002 May;30(5):525-30.
Orphenadrineis another inhibitor that is also usedfor CYP2B6 but
itsspecificity is discussed.
Check Sai Y, Dai R, Yang TJ, Krausz KW, Gonzalez FJ, Gelboin HV, Shou M.
Assessment of specificity of eight chemical inhibitors using
cDNA-expressed cytochromes P450.
Xenobiotica. 2000 Apr;30(4):327-43.
Houda
Houda Hachad, PharmD
Research Associate
Metabolism and Transport Drug Interaction Database
Department of Pharmaceutics
H272 Health Sciences Center
Box 357610
Seattle, Washington 98195-7610
206-543-4669 Fax: 206-543-3204
hhachad.-at-.u.washington.edu
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Dear Houda,
Thanks for the suggestion. I am planning to run a cocktail inhibition
analysis of the major P450s-1A2, 2B6, 2C8,9,19, 2D6, 3A4 and 2E1. Tepa
is metabolized by CYP3A4 and therefore to use it as a 2B6 inhibitor is
not very specific. alsoorphenadrineinhibits CYP2D6.-saileta
Scientist
ADME-PK
Sunesis Pharmaceuticals
341 Oyster Point Blvd
South San Francisco, CA 94080
Tel.: 650-266-3679
Fax: 650-266-3502
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Dear Dr Prabhu,
I looked up for reported CYP2B6 inhibitors on our drug interaction
database and I found an article on 2 other CYP2B6 inhibitors that are
supposed to be specific for this CYP:
Stiborova M, Borek-Dohalska L, Hodek P, Mraz J, Frei E. New selective
inhibitors of cytochromes P450 2B and their application to
antimutagenesis of tamoxifen.
Arch Biochem Biophys. 2002 Jul 1;403(1):41-9.
There are also data in the following article showing that
tranylcypromine inhibits CYP2B6 but it is not specific it inhibits 2A6
and 2E1. similarly, Methoxsalen inhibits 2A6 (Ki=0.2 uM), 2B6 (Ki=25
uM) and 2E1 (Ki=75 uM).
Zhang W, Kilicarslan T, Tyndale RF, Sellers EM.
Evaluation of methoxsalen, tranylcypromine, and tryptamine as specific
and
selective CYP2A6 inhibitors in vitro.
Drug Metab Dispos. 2001 Jun;29(6):897-902.
I hope that this will help!
Houda
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The following message was posted to: PharmPK
Hello sir,
I believe thiotepa and orphenadrine do the trick. Orphenadrine would
certainly be safer to use.
Richard Molitor, R.Ph.
http://www.angelfire.com/wa/pharmacist
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The following message was posted to: PharmPK
dear prabhu.....
Reference:
1)Triethylenethiophosphoramide is a specific inhibitor of
cytochrome P450 2B6: Implications for cyclophosphamide metabolism.
Rae JM, Soukhova NV, Flockhart DA, Desta Z
Drug Metab Dispos 2002;30(5)
2)Yang TJ, Krausz KW, Shou M, Yang SK, Buters JTM, Gonzalez FJ and
Gelboin HV (1998) Inhibitory Monoclonal Antibody to
Human
Cytochrome P450 2B6. Biochem Pharmacol 55: 1633-1640.
3)http://home.ccr.cancer.gov/metabolism/hvgccr.htm
Munvar Miya Shaik
B.Pharm(Hons.)
BITS, Pilani
Rajasthan-333031
Email: smart_munnu.-a-.yahoo.co.in
or f1999768.-at-.bits-pilani.ac.in
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