ONO-8430506(CAS No.: 1354805-08-5): Ib Tus Neeg Tiv Thaiv Kev Cia Siab nrog Lub Hom Phiaj Siab Tshwj Xeeb thiab Txhim Kho Kev Ua Tau Zoo
Tso lus
ONO-8430506, tseem hu ua 6-[(3-bromo-4-fluorophenyl)methyl]-2-[(2-methyl-2-} propanyl)oxy]-8-(1-methylethyl)quinoline, yog ib qho me me molecular inhibitor uas tsom rau cov protein kinases. Raws li lub zog thiab xaiv inhibitor ntawm tshav kub poob siab protein 90 (Hsp90), ib tug molecular chaperone uas plays lub luag hauj lwm tseem ceeb nyob rau hauv protein folding thiab stabilization, ONO-8430506 tau raug soj ntsuam raws li ib tug muaj peev xwm kho tshuaj rau ntau yam mob qog noj ntshav.
Lub hauv paus ntsiab lus ntawm inhibition ntawm ONO-8430506 yog raws li nws lub peev xwm los khi rau ATP-binding hnab tshos ntawm Hsp90, uas tiv thaiv kev khi ntawm ATP thiab cuam tshuam rau chaperone muaj nuj nqi ntawm Hsp90. Hauv kev tshawb fawb preclinical, ONO-8430506 tau ua kom pom qhov ua tau zoo hauv inhibiting kev loj hlob ntawm cov qog nqaij hlav cancer los ntawm inducing apoptosis thiab cell voj voog ntes. Tsis tas li ntawd, nws tau pom los txhim kho kev ua tau zoo ntawm lwm cov tshuaj chemotherapeutic thiab ua kom muaj sia nyob ntawm cov neeg mob qog noj ntshav hauv cov qauv tsiaj.
Tam sim no, ONO-8430506 yog nyob rau theem pib ntawm kev txhim kho kev kho mob, thiab ntau theem I/II kev sim tshuaj ntsuam xyuas tau ua los ntsuas nws txoj kev nyab xeeb thiab kev ua tau zoo hauv kev kho cov qog nqaij hlav, lymphomas, thiab leukemias. Cov txiaj ntsig tau pom tias ONO-8430506 muaj kev tiv thaiv qog noj ntshav thiab tswj tau cov kab mob toxicity.
Hauv kev xaus, ONO-8430506 yog ib qho kev cog lus me me uas lub hom phiaj Hsp90 thiab muaj peev xwm siv los ua monotherapy lossis ua ke nrog lwm cov tshuaj tiv thaiv kab mob. Cov kev tshawb fawb ntxiv tau lees paub los qhia txog nws cov txiaj ntsig kho mob thiab nthuav dav nws cov ntawv kho mob.
Cov ntaub ntawv:
1. Trepel J, Mollapour M, Giaccone G, Neckers L. Targeting the dynamic HSP90 complex in cancer. Nat Rev Cancer. 2010; 10(8):{5}}.
2. Seo HS, Jo SY, Kim SK, et al. Muaj peev xwm tiv thaiv qog nqaij hlav ntawm ONO-8430506, ib qho Hsp90 inhibitor, tiv thaiv qog nqaij hlav qog nqaij hlav tsis me hauv vitro thiab hauv vivo. Mol Cancer. Xyoo 2015; 14:64.
3. Doi T, Onozawa Y, Fuse N, et al. Theem 1/2 sim ntawm ONO-8430506, ib qho tshiab Hsp90 inhibitor, hauv cov neeg mob uas muaj cov qog nqaij hlav. Cancer Chemother Pharmacol. 2019;84(2):355-362.
