Detail for rapamycin
Basic Information
DrugID 89
DrugName rapamycin
DrugDetail Sirolimus (INN/USAN), also known as rapamycin, is an immunosuppressant drug used to prevent rejection in organ transplantation; it is especially useful in kidney transplants. It prevents activation of T cells and B-cells by inhibiting their response to interleukin-2 (IL-2). A macrolide, sirolimus was first discovered as a product of the bacterium Streptomyces hygroscopicus in a soil sample from Easter Island ?? an island also known as Rapa Nui, hence the name. It is marketed under the trade name Rapamune by Wyeth. Sirolimus was originally developed as an antifungal agent. However, this use was abandoned when it was discovered to have potent immunosuppressive and antiproliferative properties. It has since been shown to prolong the life of mice and might also be useful in the treatment of certain cancers. Unlike the similarly named tacrolimus, sirolimus is not a calcineurin inhibitor, but it has a similar suppressive effect on the immune system. Sirolimus inhibits the response to interleukin-2 (IL-2), and thereby blocks activation of T- and B-cells. In contrast, tacrolimus inhibits the secretion of IL-2. The mode of action of sirolimus is to bind the cytosolic protein FK-binding protein 12 (FKBP12) in a manner similar to tacrolimus. Unlike the tacrolimus-FKBP12 complex which inhibits calcineurin (PP2B), though, the sirolimus-FKBP12 complex inhibits the mammalian target of rapamycin (mTOR) pathway by directly binding the mTOR Complex1 (mTORC1). mTOR, which stands for "mammalian Target Of Rapamycin", has also been called FRAP (FKBP-rapamycin associated protein), RAFT (rapamycin and FKBP target), RAPT1, or SEP. The earlier names FRAP and RAFT were coined to reflect the fact that rapamycin must bind FKBP12 first, and only the FKBP12-rapamycin complex can bind mTOR. However, mTOR is now the widely accepted name, since Tor was first discovered via genetic and molecular studies of rapamycin-resistant mutants of Saccharomyces cerevisiae that identified FKBP12, Tor1, and Tor2 as the targets of rapamycin and provided robust support that the FKBP12-rapamycin complex binds to and inhibits Tor1 and Tor2.

http://en.wikipedia.org/wiki/Rapamycin

Indication For the prophylaxis of organ rejection in patients receiving renal transplants.

http://www.drugbank.ca/drugs/DB00877

Structure Click to see the orginal picture.
Interaction
Drug Name PMIDLink Reference
Amphotericin B Kontoyiannis DP, Lewis RE, Alexander BD, Lortholary O, Dromer F, Gupta KL, John GT, Del Busto R, Klintmalm GB, Somani J, Lyon GM, Pursell K, Stosor V, Munoz P, Limaye AP, Kalil AC, Pruett TL, Garcia-Diaz J, Humar A, Houston S, House AA, Wray D, Orloff S, Dowdy LA, Fisher RA, Heitman J, Albert ND, Wagener MM, Singh N. (2008) Calcineurin inhibitor agents interact synergistically with antifungal agents in vitro against Cryptococcus neoformans isolates: correlation with outcome in solid organ transplant recipients with cryptococcosis. Antimicrob Agents Chemother. 52(2):735-8.
Amphotericin B Dannaoui E, Schwarz P, Lortholary O. (2009) In vitro interactions between antifungals and immunosuppressive drugs against zygomycetes. Antimicrob Agents Chemother. 53(8):3549-51.
Fluconazole Kontoyiannis DP, Lewis RE, Alexander BD, Lortholary O, Dromer F, Gupta KL, John GT, Del Busto R, Klintmalm GB, Somani J, Lyon GM, Pursell K, Stosor V, Munoz P, Limaye AP, Kalil AC, Pruett TL, Garcia-Diaz J, Humar A, Houston S, House AA, Wray D, Orloff S, Dowdy LA, Fisher RA, Heitman J, Albert ND, Wagener MM, Singh N. (2008) Calcineurin inhibitor agents interact synergistically with antifungal agents in vitro against Cryptococcus neoformans isolates: correlation with outcome in solid organ transplant recipients with cryptococcosis. Antimicrob Agents Chemother. 52(2):735-8.
Itraconazole Dannaoui E., Schwarz P., Lortholary O. (2009) In Vitro Interactions between Antifungals and Immunosuppressive Drugs against Zygomycetes. Antimicrobial Agents and Chemotherapy 53:3549-3551. DOI: 10.1128/aac.00184-09
Posaconazole Dannaoui E., Schwarz P., Lortholary O. (2009) In Vitro Interactions between Antifungals and Immunosuppressive Drugs against Zygomycetes. Antimicrobial Agents and Chemotherapy 53:3549-3551. DOI: 10.1128/aac.00184-09
Ravuconazole Dannaoui E., Schwarz P., Lortholary O. (2009) In Vitro Interactions between Antifungals and Immunosuppressive Drugs against Zygomycetes. Antimicrobial Agents and Chemotherapy 53:3549-3551. DOI: 10.1128/aac.00184-09
Target
TargetName References EssentialGene? Link
Albendazole monooxygenase No
ATP-binding cassette sub-family B member 1 No
cDNA FLJ46716 fis, clone TRACH3018108, highly similar to 51 kDa FK506-binding protein No
CYPIIIA5 No
CYPIIIA7 No
DJ576K7.1 (FK506 binding protein 12-rapamycin associated protein 1) No
FK506 binding protein 1A, 12kDa No
FK506 binding protein 2, 13kDa No
FK506 binding protein 5 No
FK506 binding protein 5 variant No
FK506-binding protein 2 No
FK506-binding protein 3 No
FK506-binding protein 3 variant No
FK506-binding protein 4 Yes
FK506-binding protein 5 No
FKBP-12 Yes
FRAP1 variant protein No
Kappa-type opioid receptor Yes
Multidrug resistance protein 1 variant No
Peptidyl-prolyl cis-trans isomerase FKBP1A No
Peptidyl-prolyl cis-trans isomerase FKBP1B No
P-glycoprotein No
P-glycoprotein 1 No
Serine/threonine-protein kinase mTOR No
PathWay
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