| MPAKA # | Dzina lazogulitsa | Kufotokozera |
| CPD100654 | Chithunzi cha PD-169316 | PD-169316 ndi choletsa chosankha cha p38 MAPK. Imalepheretsa p38 MAPK yokhala ndi IC50 ya 89 nM. PD169316, imalepheretsa kusintha kwa kukula kwa beta-induced Smad signing m'maselo a khansa ya ovarian. |
| CPD100653 | LDN-193189 | LDN193189 ndi kamolekyu yaying'ono yamphamvu kwambiri ya BMP inhibitor yokhala ndi IC50 ya 5 ndi 30 nM ya ALK2 ndi ALK3, motsatana. LDN193189 imalepheretsanso BMP mtundu I receptors ALK6 (TGFβ1 / BMP signing) ndi SMAD phosphorylation yotsatira. |
| Chithunzi cha CPD100652 | K02288 | K02288 ndi choletsa champhamvu cha BMP siginecha. K02288 ili ndi in vitro ntchito yolimbana ndi ALK2 pamiyeso yotsika ya nanomolar yofanana ndi yomwe ikuwongolera pano LDN-193189. K02288 makamaka inaletsa BMP-induced Smad njira popanda kukhudza TGF-β siginecha ndi kuchititsa dorsalization wa zebrafish embryos. |
| CPD100650 | Mtengo wa SB-431542 | SB-431542 ndi buku laling'ono loletsa mamolekyu amtundu wa I TGF-beta receptor, pagulu la mizere yoyipa ya glioma cell. SB-431542 inatseka phosphorylation ndi translocation ya nyukiliya ya SMADs, oyimira pakati pa maselo a TGF-beta signing, ndi kuchepa kwa TGF-beta-mediated transcript. Komanso, SB-431542 inaletsa kufotokoza kwa zovuta ziwiri za TGF-beta-vascular endothelial growth factor ndi plasminogen activator inhibitor-1. |
| CPD100649 | GW788388 | GW788388 ndi mtundu watsopano wa TGF-beta I receptor inhibitor yokhala ndi mbiri yabwino kwambiri ya pharmacokinetic poyerekeza ndi SB431542. Tinaphunzira zotsatira zake mu m'galasi ndipo tinapeza kuti zinalepheretsa zonse TGF-beta mtundu I ndi mtundu II receptor kinase zochita, koma osati za mafupa ogwirizana morphogenic mapuloteni mtundu II cholandilira. Kupitilira apo, idatseka TGF-beta-induced Smad activation ndi chandamale cha jini, pomwe idachepetsa kusintha kwa epithelial-mesenchymal ndi fibrogenesis. |
| CPD100648 | Mtengo wa SB-525334 | SB525334 ndi choletsa champhamvu komanso chosankha cha kusintha kwa kukula factor-beta1 (TGF-beta1) receptor, activin receptor-like kinase (ALK5). SB525334 inaletsa ntchito ya ALK5 kinase yokhala ndi IC(50) ya 14.3 nM ndipo inali pafupifupi 4-fold zochepa mphamvu monga inhibitor ya ALK4 (IC(50) = 58.5 nM). SB-525334 inali yosagwira ntchito ngati inhibitor ya ALK2, ALK3, ndi ALK6 (IC(50)> 10,000 nM). M'maselo otengera ma cell, SB-525334 (1 microM) idatseka TGF-beta1-induced phosphorylation ndi kusuntha kwa nyukiliya kwa Smad2/3 m'maselo aimpso a proximal tubule cell ndikulepheretsa TGF-beta1-kuwonjezeka kwa plasminogen activator inhibitor-1 (PAI-1). ) ndi procollagen alpha1 (I) mRNA mawu mu A498 aimpso epithelial carcinoma maselo. |
| CPD100647 | BIBF0775 | BIBF0775 ndi inhibitor ya kusintha kukula factor β receptor I (TGFβRI). Kusanthula kapangidwe ka X-ray kunawonetsa kuti BIBF0775 idalowetsedwa mu kinase domain ya TGFβRI. |
| Chithunzi cha CPD100646 | LY3023414 | LY3023414 ndi molekyu yaing'ono yomwe yasonyezedwa mu vitro kuti ikhale yosankha ATP-competitive inhibitor ya PI3Kα ndi mTOR, DNA-PK, ndi ena am'banja la I PI3K. Mu vitro, LY3023414 yawonetsa ntchito yoletsa motsutsana ndi PI3K ndi mTOR m'maselo a chotupa, komanso antiproliferative ntchito ndi zotsatira zama cell. Kuphatikiza apo, mu vitro, LY3023414 imalepheretsa kuthekera kwa PI3K ndi mTOR ku magawo a phosphorylate munjira ya PI3K/mTOR. LY3023414 ikufufuzidwa muyeso lachipatala la gawo I. |
| Chithunzi cha CPD100645 | Onani | CC-223 ndi choletsa chopezeka pakamwa cha mammalian chandamale cha rapamycin (mTOR) chomwe chili ndi ntchito yoletsa antiineoplastic. MTOR kinase inhibitor CC-223 imalepheretsa ntchito ya mTOR, zomwe zingapangitse kulowetsedwa kwa chotupa cell apoptosis ndi kuchepa kwa kuchuluka kwa maselo a chotupa. mTOR, serine/threonine kinase yomwe imayendetsedwa muzotupa zosiyanasiyana, imakhala ndi gawo lofunikira pansi pa njira yowonetsera PI3K/AKT/mTOR, yomwe nthawi zambiri imakhala yosayendetsedwa ndi khansa ya anthu. |
| Chithunzi cha CPD100644 | Bimiralisib | Bimiralisib, yomwe imadziwikanso kuti PQR309, ndi inhibitor ya pakamwa ya phosphoinositide-3-kinases (PI3K) komanso inhibitor ya chandamale cha mammalian cha rapamycin (mTOR), chomwe chingathe kuchitapo kanthu. PI3K/mTOR kinase inhibitor PQR309 imalepheretsa PI3K kinase isoforms alpha, beta, gamma ndi delta ndipo, pang'ono, mTOR kinase, zomwe zingapangitse chotupa cell apoptosis ndi kulepheretsa kukula m'maselo mopambanitsa PI3K/mTOR. Kutsegula kwa njira ya PI3K/mTOR kumalimbikitsa kukula kwa maselo, kukhala ndi moyo, komanso kukana mankhwala amphamvu a chemotherapy ndi radiotherapy. |
| CPD100643 | CZ415 | CZ415 ndi yamphamvu ya ATP-mTOR inhibitor yokhala ndi kusankha kosaneneka kuposa kinase ina iliyonse (IC50 = 14.5 nM IC50 ya pS6RP ndi 14.8 nM ya pAKT) yokhala ndi ma cell permeability (Kd app = 6.9 nM). Makhalidwe a pharmacokinetic ovomerezeka mwapang'onopang'ono komanso kupezeka kwabwino kwapakamwa kunawonetsa kukwanira kwa CZ415 pakupititsa patsogolo maphunziro a vivo. CZ415 imayimira molekyulu yabwino pakufufuza zamankhwala kwa gawo la mTOR pathophysiological mu vivo. |
| Chithunzi cha CPD100642 | GDC-0084 | GDC-0084, yomwe imadziwikanso kuti RG7666 ndi Paxalisib, ndi phosphatidylinositol 3-kinase (PI3K) inhibitor yomwe ingathe kuchitapo kanthu. PI3K inhibitor GDC-0084 makamaka imalepheretsa PI3K mu PI3K/AKT kinase (kapena protein kinase B) njira yowonetsera, motero imalepheretsa kuyambitsa kwa PI3K njira yowonetsera. Izi zitha kulepheretsa kukula kwa ma cell komanso kukhala ndi moyo m'ma cell a chotupa. Kutsegula kwa njira yowonetsera PI3K nthawi zambiri kumalumikizidwa ndi tumorigenesis. |
| Chithunzi cha CPD100641 | Chithunzi cha CC-115 | CC-115 ndi inhibitor yapawiri ya DNA-dependent protein kinase (DNA-PK) ndi chandamale cha mammalian cha rapamycin (mTOR), chomwe chingathe kuchitapo kanthu pa anti-antineoplastic. CC-115 imamangiriza ndikuletsa ntchito ya DNA-PK ndi onse a raptor-mTOR (TOR complex 1 kapena TORC1) ndi rictor-mTOR (TOR complex 2 kapena TORC2), zomwe zingayambitse kuchepa kwa kuchuluka kwa ma cell a khansa omwe akuwonetsa. DNA-PK ndi TOR. DNA-PK, serine/threonine kinase komanso membala wa PI3K-related kinase subfamily ya protein kinases, imayatsidwa pakuwonongeka kwa DNA ndipo imagwira ntchito yofunika kwambiri pakukonzanso zosweka za DNA zamitundu iwiri kudzera munjira ya DNA nonnhomologous end joining (NHEJ) . |
| CPD100640 | XL388 | XL388 ndi Kalasi Yatsopano Yamphamvu Kwambiri, Yosankha, ATP-Mpikisano, ndi Olly Bioavailable Inhibitors ya Mammalian Target of Rapamycin (mTOR). XL388 inhibited cellular phosphorylation ya mTOR complex 1 (p-p70S6K, pS6, ndi p-4E-BP1) ndi mTOR complex 2 (pAKT (S473)) magawo. XL388 idawonetsa ma pharmacokinetics abwino komanso kuwonekera kwapakamwa pamitundu ingapo yokhala ndi bioavailability wapakatikati. Kuwongolera pakamwa kwa XL388 kwa mbewa zamaliseche za athymic zobzalidwa ndi chotupa chamunthu xenografts kunapereka ntchito yayikulu komanso yodalira mlingo. |
| CPD100639 | GDC-0349 | GDC-0349 ndi kamolekyu kakang'ono ka anticaner drug candidate, yopangidwa ndi Genentech. Pofika mu July 2012, Genentech yapereka mayesero a gawo loyamba la GDC-0349 pofuna kuyesa Chitetezo ndi Kupirira kwa GDC-0349 mu Odwala Omwe Ali ndi Zotupa Zapamwamba Zapamwamba kapena Metastatic Solid kapena Non Hodgkin's Lymphoma. |
| CPD100638 | Chithunzi cha ETP-46464 | ETP46464 ndi inhibitor ya DNA damage response kinase Ataxia-telangiectasia mutated (ATM)- and Rad3-related (ATR). |
| CPD100637 | NJIRA-600 | WAY-600 ndi choletsa champhamvu, cha ATP-mpikisano komanso chosankha cha mTOR chokhala ndi IC50 ya 9 nM |
| CPD100636 | WYE-687 | WYE-687 ndi choletsa champhamvu komanso cha ATP-chopikisana komanso chosankha cha mTOR chokhala ndi IC50 ya 7 nM. |
| Chithunzi cha CPD100635 | Palomid-529 | Palomid 529, yomwe imadziwikanso kuti P529, ndi buku la PI3K/Akt/mTOR inhibitor. Palomid 529 (P529) imalepheretsa TORC1 ndi TORC2 zovuta ndikuwonetsa kuletsa kwa Akt kusaina ndi chizindikiro cha mTOR chimodzimodzi mu chotupa ndi mitsempha. Zinawonetsedwa kuti P529 inaletsa kukula kwa chotupa, angiogenesis, ndi kufalikira kwa mitsempha. Inasunganso mbali zopindulitsa za chotupa cha vascular normalization chomwe rapamycin amadzitamandira. Komabe, P529 idawonetsa phindu lowonjezera la kutsekereza siginecha ya pAktS473 yogwirizana ndi kutsekereza TORC2 m'maselo onse ndikudumphadumpha zolumikizira zomwe zimatsogolera pakuwonjezeka kwa chizindikiro cha Akt m'maselo ena otupa. (Chitsime: Cancer Res 008; 68 (22): 9551?-7). |
| Chithunzi cha CPD100634 | BGT226-maleate | BGT226 ndi phosphatidylinositol 3-kinase (PI3K) inhibitor yomwe ingathe kuchitapo kanthu. PI3K inhibitor BGT226 imaletsa makamaka PIK3 mu PI3K/AKT kinase (kapena protein kinase B) njira yowonetsera, yomwe ingayambitse kusamutsidwa kwa cytosolic Bax kupita ku nembanemba yakunja ya mitochondrial, kuonjezera kupitirira kwa mitochondrial membrane; Kufa kwa ma cell a apoptotic kumatha kuchitika. Bax ndi membala wa gulu la proapoptotic Bcl2 la mapuloteni. |
| CPD100633 | WYE-125132 | WYE-125132, yomwe imadziwikanso kuti WYE-132, ndi yamphamvu kwambiri, yopikisana ndi ATP, komanso yeniyeni ya mTOR kinase inhibitor (IC(50): 0.19 +/- 0.07 nmol/L; > 5,000-fold selective against PI3Ks). WYE-132 yoletsa mTORC1 ndi mTORC2 mumitundu yosiyanasiyana ya khansa mu vitro ndi mu vivo. Chofunika kwambiri, chogwirizana ndi kusintha kwa majini kwa mTORC2, WYE-132 yolunjika P-AKT(S473) ndi ntchito ya AKT popanda kuchepetsa kwambiri chiwerengero cha PI3K/PDK1 biomarker P-AKT(T308), kuwonetsa lamulo lodziwika bwino komanso lolunjika. AKT ndi mTORC2 m'maselo a khansa. |
| CPD100632 | Vistusertib | Vistusertib, yomwe imadziwikanso kuti AZD2014, ndi inhibitor yoletsa pakamwa ya mammalian target of rapamycin (mTOR) yokhala ndi mphamvu yoletsa antiineoplastic. mTOR kinase inhibitor AZD2014 imalepheretsa ntchito ya mTOR, zomwe zingapangitse kulowetsedwa kwa chotupa cell apoptosis ndi kuchepa kwa kuchuluka kwa maselo otupa. mTOR, serine/threonine kinase yomwe imayendetsedwa muzotupa zosiyanasiyana, imakhala ndi gawo lofunikira kumunsi kwa PI3K/Akt/mTOR njira yowonetsera. |
| Chithunzi cha CPD100631 | WYE-354 | WYE-354 ndi choletsa champhamvu cha cell-permeable cha mTOR (IC50 = 4.3 nM) chomwe chimatchinga kusaina kudzera m'mTOR complex 1 (mTORC1) ndi mTORC2. |
| CPD100630 | Gedatolisib | Gedatolisib, yemwe amadziwikanso kuti PKI-587 ndi PF-05212384, ndi wothandizira omwe amayang'ana phosphatidylinositol 3 kinase (PI3K) ndi chandamale cha mammalian cha rapamycin (mTOR) munjira yosainira ya PI3K/mTOR, yomwe ingathe kuchitapo kanthu. Pakuwongolera m'mitsempha, PI3K/mTOR kinase inhibitor PKI-587 imaletsa PI3K ndi mTOR kinases, zomwe zingayambitse apoptosis ndi kulepheretsa kukula kwa ma cell a khansa mopitilira muyeso PI3K/mTOR. Kutsegula kwa njira ya PI3K/mTOR kumalimbikitsa kukula kwa maselo, kupulumuka, ndi kukana mankhwala a chemotherapy ndi radiotherapy; mTOR, serine/threonine kinase kunsi kwa PI3K, ikhozanso kutsegulidwa popanda PI3K. |
