14. Nuovi sviluppi per il futuro
14.4 Conclusioni
Sebbene sia stato dimostrato l’ampio coinvolgimento di diverse protein chinasi nell’asma e nella BPCO, non è stato ancora approvato l’utilizzo di nessun farmaco inibitore e le ricerche non hanno ancora raggiunto la fase 3. Al momento si stanno portando avanti molti studi preclinici nella speranza di avviare al più presto le prime sperimentazioni in vivo. Un altro passo molto importante da raggiungere è
sicuramente lo sviluppo di composti ad attività chinasica-inibitoria somministrabili per inalazionein modo da evitare il più possibile l’esposizione sistemica, traguardo che al momento è ancora molto lontano a causa della difficoltà realizzativa di tale tipologia di somministrazione. Poiché fin ora gli sforzi nel trovare nuove terapie per la cura dell’asma grave e della BPCO abbiano portato risultati piuttosto
insoddisfacenti, si spera che in un futuro prossimo l’industria farmaceutica investa significativamente in questo settore.
Abbreviazioni:
AHR,iperreattività delle vie respiratorie;
AMPK, protein chinasi attivata dall’adenosina monofosfato;
AP-1, attivatore proteico-1;
ASK, apoptosis signal-regulatory kinase; ATP, adenosina tri-fosfato;
AZD2014, [3-(2,4 bis((S)-3-metilmorfolino)pirido[2,3-d]pirimidin-7-yl)-N- metilbenzammide];
BAY 65-1942, ((7E)-7-[2-(ciclopropilmetossil)-6-oxocicloesano-2,4-dien-1-ilidene]-5- [(3S)-piperidin-3-ilidene]-4,8-diidro-1H-pirido[2,3-d][1,3]ossazina-2-one)];
BTK, tirosin-chinasi di Bruton;
BPCO, bronco pneumopatia cronica ostruttiva; CXCL8, interleuchina-8;
EGFR, fattore di crescita per l’epidermide;
ERK, extracellular regulating kinase;
FEV1, volume espiratorio massimo nel 1 secondo; FGFR, recettori dei fattori di crescita dei fibroblasti;
GM-CSF, fattore stimolante le colonie granulocitarie-macrofagiche; GR, recettore del glucocorticoide;
GSK2269557, [2-(6-(1H-indolo-4-yl)-1H-indazol-4-yl)-5-((4-isopropilpiperazina-1- yl)metil)ossazolo-idrocloruro];
GSK3beta, glicogeno sintasi chinasi 3beta; Hck, hematopoietic cell kinase;
HDAC-2, istone deacetilasi-2; Hsp, proteina da shock termico;
IFN, Interferone;
IgE, immunoglobulina E;
IKK, inibitore protein chinasi Kb; IL, interleuchina;
IRAK, chinasi associate al recetore per l’interleuchina-1;
ITAM, immunoreceptor-tyrosine-based activation motif; JAK, Janus chinasi;
JNK, Jun NH2-terminal kinase;
LAS189386, [1-{2-[(1S,4S)-2,5-diazbiciclo[2.2.1]epta-2-yl]piridin-4-yl}-N-pirazin- 2-yl-1H-indazol-3-ammino];
LPS, lipopolisaccaride;
LY294002, [2-morfolin-4-yl-8-cromofenil-4-one]; MAPK, mitogen-activated protein kinase;
MAPKAPK o MK2, MAP-activated protein kinase; MKP, MAP kinase fosfatasi;
mTOR, mammalian target of rapamycin; NF-kB, fattore nucleare Kappa-B;
NIK, NF-kB-inducing kinase;
PBMC, cellule mononucleate del sangue periferico;
PD-98059, [2’-amino-3’-metossiflavone];
PDGF(R), recettore del fattore di crescita derivato dalle piastrine;
PH797804, [(aS)-3-[3-bromo-4-[(2,4difluorobenzil) ossil]-6-metil-2-oxopiridin- 1(2H)-yl]-N,4-dimetilbenzamide;
PI3K, fosfoinositolo-3-chinasi; PKC, protein chinasi C;
PTEN, phosphatase and tensin homolog deleted from chromosome 10; ROCK, Rho-associated protein kinase;
RTK, recettore tirosin-chinasico; S6K, chinasi ribosomiale S6;
SB-505154, [2-(5-benzo[1,3] diossol-5-yl-2-tert-butil-3H-imidiazol-4-yl)-6- metilpiridin cloridrato;
SD-282, indolo-5-carbossammide;
SHIP, Src homology 2 domain-containing inositol 5’-phosphatase;
STAT, proteina trasduttrice del segnale ed attivatrice della trascrizione; Syk, tirosin chinasi splenica;
TAK, transforming growth factor-beta-activated kinase 1;
TG100-115, (3-[2,4-diammino-6-(3-idrossifenil)pteridin-2,4-diammina))]; TGF, fattore di crescita trasformante;
TLR, recettori toll-like;
TNF, fattore di necrosi tumorale;
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