mTOR

CAT # Ingoa Hua Whakaahuatanga
CPD100654 PD-169316 Ko te PD-169316 he aukati whiriwhiri o p38 MAPK. Ka whakakorehia te p38 MAPK me te IC50 o te 89 nM. Ko te PD169316, he aukati i te whakahuri i te tauwehe tipu beta-whakaawe i te tohu Smad i roto i nga pūtau mate pukupuku ovarian tangata.
CPD100653 LDN-193189 Ko te LDN193189 he tino kaha te aukati BMP ngota iti me te IC50 o 5 me te 30 nM mo ALK2 me ALK3, ia. Ko te LDN193189 ano hoki ka aukati i nga kaiwhakawhiwhi BMP momo I ALK6 (tohu TGFβ1 / BMP) me te phosphorylation SMAD muri.
CPD100652 K02288 Ko K02288 he aukati kaha o te tohu BMP. Ko te K02288 he mahi in vitro ki te ALK2 i nga kohinga nanomolar iti e rite ana ki te roopu mata o naianei LDN-193189. Ko te K02288 i aukati i te huarahi Smad i whakaawehia e te BMP me te kore e pa ki te tohu tohu TGF-β me te whakangao i te dorsalization o nga embryos zebrafish
CPD100650 SB-431542 Ko te SB-431542 he pūrākau aukati ngota ngota iti o te momo I TGF-beta kaiawhina, kei runga i te roopu o nga raina pūtau glioma kino tangata. I aukati te SB-431542 i te phosphorylation me te whakawhiti karihi o nga SMAD, nga kaiwawao intracellular o te tohu tohu TGF-beta, me te whakaheke i te whakawhitinga TGF-beta-mediated. I tua atu, ka whakakorehia e te SB-431542 te whakapuakitanga o nga kaitautoko e rua o te TGF-beta-vascular endothelial tipu tipu me te plasminogen activator inhibitor-1.
CPD100649 GW788388 Ko te GW788388 he kaiwhakahauhau hou TGF-beta momo I hou me te ahua pai ake o te rongoa rongoa ki te SB431542. I akohia e matou tona paanga i roto i te vitro ka kitea he aukati i nga mahi e rua o te TGF-beta momo I me te momo II receptor kinase, engari ehara i te mea o te wheua morphogenic pūmua momo II receptor. I tua atu, i aukatihia e te TGF-beta-induced Smad activation and target expression ira, i te whakaheke i nga whakawhitinga epithelial-mesenchymal me te fibrogenesis.
CPD100648 SB-525334 Ko te SB525334 he aukati kaha me te whiriwhiri o te huringa tipu-beta1 (TGF-beta1) kaiawhina, activin receptor-like kinase (ALK5). I aukatihia e SB525334 te mahi kinase ALK5 me te IC(50) o 14.3 nM me te 4-tiki iti ake te kaha hei aukati i te ALK4 (IC(50) = 58.5 nM). Ko te SB-525334 kaore i te kaha hei aukati o ALK2, ALK3, me ALK6 (IC(50)> 10,000 nM). I roto i nga whakamatautau i runga i te pūtau, ka aukati a SB-525334 (1 microM) i te phosphorylation a te TGF-beta1 me te whakawhiti karihi o Smad2 / 3 i roto i nga renal tubule proximal me te aukati i te piki o te TGF-beta1 i roto i te plasminogen activator inhibitor-1 (PAI-1). ) me te whakaaturanga procollagen alpha1(I) mRNA i roto i te A498 renal epithelial pūtau mate pukupuku.
CPD100647 BIBF0775 Ko te BIBF0775 he aukati o te huringa tipu β receptor I (TGFβRI). I whakaatuhia e te tātaritanga hanganga X-ray ko te BIBF0775 i uru ki te rohe kinase o TGFβRI
CPD100646 LY3023414 Ko te LY3023414 he ngota ngota iti kua whakaatuhia i roto i te in vitro hei aukati ATP-whakataetae whiriwhiri o PI3Kα me te mTOR, DNA-PK, me etahi atu mema o te whanau o te akomanga I PI3K. In vitro, kua whakaatu a LY3023414 i te mahi aukati ki te PI3K me te mTOR i roto i nga pūtau puku, me te mahi antiproliferative me nga paanga o te huringa pūtau. I tua atu, in vitro, LY3023414 inhibits the ability of PI3K and mTOR to phosphorylate substrates in the PI3K/mTOR pathway. Kei te tirotirohia a LY3023414 i tetahi whakamatautau haumanu o te wahanga I.
CPD100645 Onatasertib Ko te CC-223 he aukati e waatea ana ki te waha o te whainga whakangote o te rapamycin (mTOR) me te mahi antineoplastic pea. Ko te aukati kinase mTOR CC-223 ka aukati i te mahi a te mTOR, ka puta pea te whakauru o te apoptosis pūtau puku me te heke o te tipu o te pūtau puku. Ko te mTOR, he kinase serine/threonine e whakahoa ana i roto i nga momo pukupuku, he mahi nui ki raro i te awa i roto i te huarahi tohu tohu PI3K/AKT/mTOR, he maha nga wa e whakahekehia ana i roto i nga mate pukupuku tangata.
CPD100644 Bimiralisib Ko te Bimiralisib, e mohiotia ana ko PQR309, he aukati paraharaha-a-waha o te phosphoinositide-3-kinases (PI3K) me te aukati o te whainga mammalian o te rapamycin (mTOR), me te mahi antineoplastic pea. PI3K/mTOR kinase inhibitor PQR309 inhibits the PI3K kinase isoforms alpha, beta, gamma and delta and, to a little extent, mTOR kinase, that may result in tumor cell cell apoptosis and growth inhibition in cells overexpressing PI3K/mTOR. Ko te whakahohenga o te ara PI3K/mTOR e whakatairanga ana i te tipu o te pūtau, te oranga, me te ātete ki te chemotherapy me te radiotherapy.
CPD100643 CZ415 Ko te CZ415 he aukati mTOR whakataetae ATP-whakataetae kaha me te kowhiringa o mua ki runga i etahi atu kinase (IC50 = 14.5 nM IC50 mo te pS6RP me te 14.8 nM mo te pAKT) he tino pai te uruhanga pūtau (Kd app = 6.9 nM). Ko nga ahuatanga pharmacokinetic o te waatea ngawari me te pai o te koiora-a-waha e whakaatu ana i te pai o te CZ415 mo te haere whakamua ki nga rangahau in vivo. Ko te CZ415 e tohu ana i tetahi rauropi pai mo te tirotiro rongoa mo te mahi pathophysiological mTOR i roto i te vivo.
CPD100642 GDC-0084 Ko te GDC-0084, e mohiotia ana ko RG7666 me Paxalisib, he phosphatidylinositol 3-kinase (PI3K) aukati me te mahi antineoplastic pea. Ko te kaitautoko PI3K GDC-0084 ka tino whakakorehia te PI3K i roto i te PI3K / AKT kinase (te protein kinase B ranei) te huarahi tohu tohu, na reira ka aukati i te whakahohe i te huarahi tohu tohu PI3K. Ka hua pea tenei ki te aukati i te tipu o nga pūtau e rua me te ora i roto i nga taupori pūtau puku whakaraerae. Ko te whakahoahoatanga o te ara tohu tohu PI3K he maha nga wa e pa ana ki te tumorigenesis.
CPD100641 CC-115 Ko te CC-115 he aukati takirua o te kinase pūmua e whakawhirinaki ana ki te DNA (DNA-PK) me te whainga mammalian o te rapamycin (mTOR), me te mahi antineoplastic pea. Ka herea e te CC-115 me te aukati i te mahi a te DNA-PK me te raptor-mTOR e rua (TOR complex 1 or TORC1) me te rictor-mTOR (TOR complex 2 or TORC2), tera pea ka whakahekehia te tipu o te pūtau o nga pūtau mate pukupuku e whakaatu ana. DNA-PK me TOR. Ko te DNA-PK, he serine/threonine kinase me te mema o te PI3K-related kinase subfamily of protein kinases, ka whakahohehia i runga i te kino o te DNA me te whai waahi nui ki te whakatika i nga wehenga DNA-a-rua ma te ara o te DNA nonhomologous end joining (NHEJ) ara. .
CPD100640 XL388 Ko te XL388 he Karaehe Panui o te Tino Kaha, Tohua, ATP-Whakataetae, me nga Kaipupuri A-waha mo te Mammalian Target o Rapamycin (mTOR). I whakakorehia e XL388 te phosphorylation pūtau o te mTOR matatini 1 (p-p70S6K, pS6, me te p-4E-BP1) me te mTOR matatini 2 (pAKT (S473)) nga taputapu. I whakaatu a XL388 i te pai o te rongoora me te whakakitenga waha i roto i nga momo maha me te pai o te koiora. Ko te whakahaere a-waha o XL388 ki nga kiore tahanga athymic i whakatohia ki nga xenografts puku tangata, he nui te mahi antitumor e whakawhirinaki ana ki te horopeta.
CPD100639 GDC-0349 Ko te GDC-0349 he kaitono tarukino anticaner ngota iti, i whakawhanakehia e Genentech. I te marama o Hūrae 2012, kua tukuna e Genentech te whakamatautau i te wahanga I o GDC-0349 mo te arotake i te Haumaru me te Whakaaetanga o GDC-0349 i roto i nga turoro me nga mate pukupuku o te rohe, metastatic totoka ranei, ko te kore Hodgkin's Lymphoma.
CPD100638 ETP-46464 Ko te ETP46464 he aukati o te kinase whakautu kino DNA kinase Ataxia-telangiectasia mutated (ATM)- me Rad3-related (ATR).
CPD100637 ARA-600 Ko te WAY-600 he kaha, he ATP-whakataetae me te aukati whiriwhiri mo te mTOR me te IC50 o 9 nM
CPD100636 WYE-687 Ko te WYE-687 he kaha me te ATP-whakataetae me te aukati whiriwhiri o te mTOR me te IC50 o 7 nM.
CPD100635 Palomid-529 Ko Palomid 529, e mohiotia ana ko P529, he pukapuka PI3K/Akt/mTOR aukati. Ko te Palomid 529 (P529) te aukati i te TORC1 me te TORC2 matatini me te whakaatu i te aukati i te tohu Akt me te tohu mTOR i roto i te pukupuku me te vasculature. I whakaatuhia ko te P529 te aukati i te tipu o te pukupuku, te angiogenesis, me te uruhanga vascular. I mau tonu i a ia nga ahuatanga whai hua o te whakapumautanga o te mate pukupuku e whakanuia ana e te rapamycin. Heoi, i whakaatu a P529 i te painga taapiri o te aukati i te tohu pAktS473 e rite ana ki te aukati i te TORC2 i roto i nga pūtau katoa, na reira ka takahi i nga kopae urupare e arai atu ai ki te piki haere o te tohu Akt ki etahi o nga pūtau puku. (Source: Cancer Res 008;68(22):9551?–7).
CPD100634 BGT226-tane Ko te BGT226 he aukati phosphatidylinositol 3-kinase (PI3K) me te mahi antineoplastic pea. Ko te PI3K inhibitor BGT226 ka tino whakakorehia te PIK3 i roto i te PI3K / AKT kinase (te protein kinase B) te tohu tohu, ka taea pea te whakawhitinga o te cytosolic Bax ki te membrane o waho o te mitochondrial, te whakanui ake i te uruhanga membrane mitochondrial; ka mate pea te mate o te pūtau apoptotic. Ko Bax tetahi mema o te whanau Bcl2 proapoptotic o nga pūmua.
CPD100633 WYE-125132 Ko te WYE-125132, e mohiotia ana ko WYE-132, he tino kaha, he ATP-whakataetae, me te motuhake mTOR kinase inhibitor (IC(50): 0.19 +/- 0.07 nmol/L; > 5,000-fold selective versus PI3Ks). I aukati a WYE-132 i te mTORC1 me te mTORC2 i roto i nga tauira mate pukupuku kanorau i roto i te vitro me te in vivo. Ko te mea nui, he rite tonu ki te whakahekenga ira o te mTORC2, WYE-132 i whaaia te P-AKT(S473) me te mahi AKT me te kore e tino whakaiti i te taumata o te PI3K/PDK1 mahi biomarker P-AKT(T308), e whakaatu ana i tetahi ture nui me te tika. o AKT na mTORC2 i roto i nga pūtau mate pukupuku.
CPD100632 Vistusertib Ko te Vistusertib, e mohiotia ana ko AZD2014, he aukati koiora-a-waha mo te whainga maminga o te rapamycin (mTOR) me te mahi antineoplastic pea. Ko te aukati kinase mTOR AZD2014 ka aukati i te mahi a te mTOR, ka puta pea te whakauru o te apoptosis pūtau puku me te heke o te tipu o te pūtau puku. Ko te mTOR, he kinase serine/threonine e whakanekehia ana i roto i nga momo pukupuku, ka whai waahi nui ki raro i te awa i roto i te huarahi tohu PI3K/Akt/mTOR.
CPD100631 WYE-354 Ko te WYE-354 he aukati pūtau-permeable kaha o te mTOR (IC50 = 4.3 nM) e aukati ana i te tohu i roto i te mTOR matatini 1 (mTORC1) me te mTORC2.
CPD100630 Gedatolisib Ko Gedatolisib, e mohiotia ana ko PKI-587 me PF-05212384, he kaihoko e aro ana ki te phosphatidylinositol 3 kinase (PI3K) me te whainga mammalian o te rapamycin (mTOR) i roto i te huarahi tohu tohu PI3K / mTOR, me te mahi antineoplastic pea. I runga i te whakahaere a-roto, ka whakakorehia e te PI3K / mTOR kinase inhibitor PKI-587 nga PI3K me te mTOR kinases, ka puta pea te apoptosis me te aukati i te tipu o nga pukupuku pukupuku e whakaatu ana i te PI3K / mTOR. Ko te whakahohe i te ara PI3K/mTOR e whakatairanga ana i te tipu o te pūtau, te oranga, me te ātete ki te chemotherapy me te radiotherapy; Ko te mTOR, he serine/threonine kinase ki raro o te PI3K, ka taea hoki te whakahohe motuhake i te PI3K.
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