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GENTAUR
Tel: +32 16 58 90 45
Fax: + 32 16 50 90 45
info@genprice.com
Av. de l'Armée 68
• B-1040 BRUSSELS • BELGIUM
GENTAUR FRANCE
Tel: 01 43 25 01 50
9, Rue Lagrange
• 75005 PARIS • FRANCE
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R-5000 Rapamycin, >99%
[RAPA] [Rapamune] [Sirolimus]
[AY-22989] [NSC-226080]
| M.W. 914.19 |
C51H79NO13
|
[53123-88-9]
RTECS: VE6250000 |
M.I. 12: 8288 |
Storage: Store at or below -20 ºC. Solubility:
Soluble in DMSO or ethanol. Disposal: A
 | Immunosuppressant, related to FK-506, but without calcineurin inhibitory
activity even when complexed to FK-506 binding protein. Selectively blocks
signalling that leads to p70 S6 kinase activation (IC50
= 50 pM). Terada, N. et al. "Failure of rapamycin to block
proliferation once resting cells have entered the cell cycle despite
inactivation of p70 S6 kinase." J. Biol. Chem. 268: 12062
(1993). Fingar, D.C. et al. "Dissociation of pp70 ribosomal protein
S6 kinase from insulin-stimulated glucose transport in 3T3-L1 adipocytes."
J. Biol. Chem. 268: 3005 (1993). Price, D.J. et al.
"Rapamycin-induced inhibition of the 70-kilodalton S6 protein kinase."
Science 257: 973 (1992). Chung, J. et al.
"Rapamycin-FKBP specifically blocks growth-dependent activation of and
signaling by the 70 kd S6 protein kinases." Cell 69: 1227
(1992). |
| Lymphokine-induced cell proliferation at the G1 phase is inhibited and
apoptosis in a murine B cell line is induced by rapamycin. Rapamycin
arrests the Saccharomyces cerevisiae cell cycle irreversibly in the
G1 phase. Morice, W.G. et al. "Rapamycin-induced inhibition of
p34cdc2 kinase activation is associated with G1/S-phase growth arrest in T
lymphocytes." J. Biol. Chem. 268: 3734 (1993). Kay, J.E.
et al. "Inhibition of T and B lymphocyte proliferation by rapamycin."
Immunology 72: 544 (1991). Heitman, J. et al.
"Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast."
Science 253: 905 (1991). |
| Due to a different mechanism of action than cyclosporin and FK506,
rapamycin may prove to be important in organ transplant patient therapy.
Fewer side effects than the standard anti-rejection treatments have been
observed. Proliferation of activated T cells is blocked by rapamycin, but
not apoptosis. The induction of rejection-causing T cell apoptosis reduces
the tendency towards transplant rejection. Schwarz, C. and Oberbauer, R.
"The future role of target of rapamycin inhibitors in renal
transplantation." Curr Opin Urol. 12: 109 (2002). Wells,
A.D. et al. "Requirement for T-cell apoptosis in the induction of
peripheral transplantation tolerance." Nat Med. 5: 1303
(1999). Li, Y. et al. "Blocking both signal 1 and signal 2 of
T-cell activation prevents apoptosis of alloreactive T cells and induction
of peripheral allograft tolerance." Nat. Med. 5: 1298 (1999).
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| On the subject of rapamycin purity: HPLC analysis of
rapamycin is somewhat complicated. Rapamycin forms several
chromatographically separable species in solution, consisting perhaps of
different conformers, tautomers, hydrates and/or isomers, but they are all
in equilibrium with the major form, trans-rapamycin. We have shown
this by collecting the individual impurity peaks in our rapamycin product
and individually re-injecting them into the HPLC. In each case, upon
re-injection the collected impurity peak is reduced or absent, and the major
peak is again trans-rapamycin, of ~95% purity or higher, thus confirming
re-quilibration back to the major trans-isomer of rapamycin.
Because we find that all significant impurities (generally, those above
0.1%) in our product, including the cis-isomer, are in equilibrium
with the trans isomer in the solution used for analysis, the actual
purity of our product is >99% rapamycin, in all of its equilibrium forms.
In contrast, material from other suppliers typically contains impurities
that do not equilibrate with trans-rapamycin, and thus are genuine
contaminants.
These results also indicate that it is probably not possible to obtain
the trans isomer in pure form, because in solution it will quickly
re-equilibrate to the mixture of cis and trans. |
| Rapamycin formulations for in vivo use: Many of
our customers have asked for information about preparing formulations of
rapamycin for administration to animals. Here are several journal citations
and links for information on this topic:
http://circ.ahajournals.org/cgi/content/full/99/16/2164 describes a
vehicle for rapamycin injection consisting of a rapamycin suspension in
0.2% carboxymethyl cellulose and 0.25% polysorbate-80. They don't say
how the suspension was done; one way is to thoroughly agitate or grind
the rapamycin in the vehicle. Another way, probably better and easier,
is to dissolve the rapamycin at high concentration in DMSO,
dimethylformamide or dimethylacetamide, then dilute into the aqueous
vehicle--this should give a very fine suspension if agitation is good
during addition of the DMSO solution. Injection was i.m. CirculationÊ
99: 2164-2170 (1999).
http://www.pnas.org/cgi/reprint/96/15/8657.pdf describes a similar
protocol; these workers dissolved the rapamycin in dimethylacetamide,
then added it in 1:24 proportion to a vehicle of (final conc.'s) 10%
polyethylene glycol (MW avg. = 400) and 17% polyloxyethylene sorbitan
monooleate. Injection was i.p. in mice, total vol. of 100 ul. Proc.
Natl. Acad. Sci. USAÊ 96: 8657-8662 (1999).
http://ajpendo.physiology.org/cgi/content/full/279/5/E1080 used 0.75
mg/kg rapamycin in 5% dimethyl sulfoxide, for injection into pigs via
jugular vein catheter. Am. J. Physiol. Endocr. Metab.Ê 279:
E1080-E1087 (2000).
http://www.bloodjournal.org/cgi/content/full/100/3/1084 injected
rapamycin in 51% wt/vol polyethylene glycol 300 (PEG300), 2.5% wt/vol
polysorbate 80, 10% vol/vol ethanol, i.p. BloodÊ 100: 1084-1087
(2002).
http://www.google.com/search?hl=en&lr=&ie=ISO-8859-1&q=%22rapamycin+injections%22
injected rapamycin i.p. in mice by diluting an ethanol stock solution of
rapamycin first into sterile 10% PEG400/8% ethanol and then that
solution was further diluted into an equal volume of sterile 10% Tween
80 for a final concentration of 20 ug rapamycin/100 ul. (Most of this
information is in the Materials and Methods section of the paper, but
the "ethanol stock solution" is mentioned under the Cell Culture and
Antibodies section, and the additional details are found in the Regrowth
Delay Assay section.) Cancer Res.Ê 62: 7291-7297 (2002).
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| See also our other standard immunosuppressant products:
| C-6000 Cyclosporin A |
| F-4900 FK-506 |
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