Sirolimus, tseem hu ua rapamycin, muag hauv cov npe xws liRapamune, yog ib qho macrolide compound siv los npog coronary stents, tiv thaiv kev hloov pauv hauv nruab nrog cev, kho cov kab mob ntsws tsawg hu ua lymphangioleiomyomatosis, thiab kho perivascular epithelioid cell hlav (PEComa) Nws muaj kev tiv thaiv kab mob hauv tib neeg lub cev thiab tshwj xeeb tshaj yog muaj txiaj ntsig zoo hauv kev tiv thaiv lub raum hloov pauv tsis lees txais. . Nws yog lub hom phiaj ntawm kev ua haujlwm ntawm rapamycin kinase (mTOR) inhibitors thiab inhibits lawv txoj kev ua haujlwm los ntawm kev txo qhov rhiab heev ntawm T thiab B hlwb rau interleukin -2 (IL-2)
Immunosuppressant
Rapamycin (Rapa) yog ib qho tshuaj tiv thaiv kab mob macrolide tshiab. Nws yog cov khoom siv dawb dawb nrog lub ntsiab lus melting ntawm {{0}} degree . Nws yog lipophilic. Nws yog yaj hauv cov kuab tshuaj organic xws li methanol, ethanol, acetone, thiab chloroform. Nws yog me ntsis soluble hauv dej thiab yuav luag insoluble hauv ether. Nws tau tsim thaum ntxov li xyoo 1970. Nws yog thawj zaug siv los ua tshuaj tiv thaiv kab mob uas tsis muaj tshuaj lom. Nws tau pom tias muaj cov tshuaj tiv thaiv kab mob hauv xyoo 1977. Rapa tau sim ua cov tshuaj tshiab rau kev kho mob ntawm kev hloov pauv hauv nruab nrog cev hauv xyoo 1989. Los ntawm cov txiaj ntsig ntawm kev sim tsiaj thiab kev siv tshuaj kho mob, nws yog ib qho tshuaj tiv thaiv kab mob tshiab nrog cov nyhuv curative zoo, tsis muaj tshuaj lom. , thiab tsis muaj nephrotoxicity. Tam sim no nws yog feem ntau siv los ua tshuaj los tswj lub cev tiv thaiv kab mob ntawm cov kab mob hauv lub cev (tshwj xeeb tshaj yog hloov lub raum) kom txo qis kev tiv thaiv kab mob tom qab hloov khoom nruab nrog cev. Txawm li cas los xij, cov kws tshawb fawb tsis ntev los no pom lwm qhov kev siv: nws tuaj yeem siv los kho Alzheimer's disease (Alzheimer's disease). Dab tsi txaus siab rau lawv yog tias lub ntsiab lus tseem ceeb ntawm rapamycin tseem muaj nyob rau hauv cov khoom siv kab mob hauv cov av sib cais ntawm cov kob sawv rov los. Cov kev sim zaum kawg no tau pom tias cov tshuaj tuaj yeem rov qab muaj peev xwm paub txog qhov tsis xws luag thaum siv rau cov nas muaj kab mob. Rapamycin yog ib qho tshuaj tua kab mob macrolide, uas zoo ib yam li cov qauv ntawm paroxetine (FK506) tab sis muaj qhov sib txawv ntawm cov tshuaj tiv thaiv kab mob. FK506 inhibits qhov kev loj hlob ntawm T lymphocytes los ntawm theem G0 mus rau theem G1, thaum Rapa thaiv cov teeb liab hloov mus los ntawm cov cytokine receptors sib txawv thiab thaiv cov txheej txheem ntawm T lymphocytes thiab lwm lub hlwb los ntawm theem G1 mus rau theem S. Piv nrog FK506, Rapa tuaj yeem thaiv calcium-dependent thiab calcium-independent teeb liab transduction txoj kev ntawm T lymphocytes thiab B lymphocytes. Cov kws tshawb fawb txog kev kho mob ntawm University of Chicago tau siv cov tshuaj rapamycin qhov ncauj thiab cov kua txiv kab ntxwv los kho melanoma, ib hom kab mob qog nqaij hlav hauv Tebchaws Europe thiab Asmeskas, uas tuaj yeem txhim kho cov nyhuv anticancer ntawm lwm cov tshuaj khomob thiab ua kom lub sijhawm muaj sia nyob ntawm cov neeg mob. Cov kev tshawb fawb pom tau hais tias rapamycin yog yooj yim decomposed los ntawm enzymes tom qab nkag mus rau hauv lub digestive ib ntsuj av, thiab kua txiv hmab txiv ntoo muaj ib tug loj tus naj npawb ntawm furanocoumarins, uas yuav inhibit qhov kev puas tsuaj ntawm digestive ib ntsuj av enzymes ntawm rapamycin, yog li nws muaj peev xwm txhim kho lub bioavailability ntawm rapamycin. Nws tau hais tias thawj zaug cov kws kho mob Dutch tau pom tias cov kua txiv kab ntxwv tuaj yeem txhim kho qhov nqus ntawm qhov ncauj ntawm Shaming. Tam sim no cov kws kho mob hauv Tebchaws Europe thiab Asmeskas siv nws rau kev npaj rapamycin.
Targeted tshuaj rau kev kho mob cancer
Cov kev tshawb fawb tsis ntev los no tau pom tias rapamycin lub hom phiaj protein (mTOR) yog ib qho intracellular kinase, thiab qhov txawv txav ntawm nws txoj kev coj ua tuaj yeem ua rau muaj ntau yam kab mob. Rapamycin, raws li lub hom phiaj inhibitor ntawm mTOR, tuaj yeem siv los kho cov qog uas cuam tshuam nrog txoj hauv kev no, suav nrog lub raum cell carcinoma, lymphoma, mob ntsws cancer, mob qog noj ntshav, mob qog noj ntshav, mob qog noj ntshav, neuroendocrine carcinoma, thiab mob plab hnyuv. Tshwj xeeb tshaj yog rau kev kho mob ntawm ob yam kab mob tsis tshua muaj, Lam thiab TSC (tuberous sclerosis), Lam thiab TSC tuaj yeem suav tias yog cov kab mob neoplastic rau qee qhov.
Coronary stent txheej
Cov nyhuv antiproliferative ntawm sirolimus kuj tau ua ke nrog coronary stents los tiv thaiv coronary restenosis tom qab balloon angioplasty. Sirolimus yog tsim los ntawm cov txheej txheem polymer los muab kev tswj kev tso tawm thaum kho tom qab kev cuam tshuam ntawm coronary. Ntau qhov kev tshawb fawb soj ntsuam loj tau pom tias cov neeg mob kho nrog sirolimus-eluting stents muaj qhov txo qis ntawm restenosis piv nrog liab qab-hlau stents, yog li txo qis dua kev phais. Lub sirolimus-eluting coronary stent yog muag raws li lub npe lag luam cipher los ntawm Cordis ntawm Johnson & Johnson. [9] Txawm li cas los xij, xws li stents kuj tseem tuaj yeem ua rau muaj kev pheej hmoo ntawm vascular thrombosis.
Vascular malformation
Sirolimus yog siv los kho vascular malformations. Kev kho mob Sirolimus tuaj yeem txo qhov mob thiab tag nrho ntawm vascular malformations, txhim kho cov ntshav coagulation thiab ua kom qeeb ntawm kev loj hlob ntawm cov hlab ntsha lymphatic. sirolimus yog ib qho tshuaj tshiab rau kev kho mob vascular malformations nyob rau hauv xyoo tas los no, sirolimus tau dhau los ua kev kho mob tshiab rau cov qog nqaij hlav vascular thiab vascular malformations. Raws li lub hom phiaj ntawm cov tsiaj nyeg ntawm rapamycin (mTOR), sirolimus tuaj yeem ua ke cov cim qhia los ntawm PI3K / Akt txoj hauv kev los tswj cov cell loj hlob thiab kev loj hlob. Yog li ntawd, sirolimus yog ib qho kev xaiv zoo tshaj plaws rau cov kab mob vascular proliferative los ntawm kev tswj cov ntaub so ntswg overgrowth teeb meem tshwm sim los ntawm kev ua kom tsis raug ntawm PI3K / Akt / mTOR txoj hauv kev ua cov tshuaj tiv thaiv kab mob.