Raws li kev tshawb fawb luam tawm hauvCell,Cov kws tshawb fawb tau tsim ib qho inhibitor tshwj xeeb rau KRASG12C hu ua ARS-1602 uas ua rau cov qog nqaij hlav hauv cov nas.
"Qhov kev tshawb fawb no muab pov thawj hauv vivo uas cov mutant KRAS tuaj yeem xaiv tau lub hom phiaj, thiab nthuav tawm ARS-1620 uas yog sawv cev rau tiam tshiab ntawm KRASG12C-specific inhibitors nrog kev cog lus muaj peev xwm kho tau," sau tseg tus thawj coj, Matthew R Janes, PhD, los ntawm Wellspring Biosciences hauv San Diego, CA, thiab cov npoj yaig.
KRAS kev hloov pauv yog qhov feem ntau hloov pauv oncogene thiab kev tshawb fawb ua ntej tau pom tias kwv yees li 30% ntawm cov qog muaj RAS hloov pauv. Cov kev hloov pauv tshwj xeeb KRAS tseem nyob hauv qee hom qog. Piv txwv li KRASG12C yog ib qho kev hloov pauv tseem ceeb hauv cov qog nqaij hlav qog nqaij hlav tsis me (NSCLC), thiab nws kuj pom muaj nyob rau hauv pancreatic thiab colectal adenocarcinomas.
Txawm hais tias muaj ntau thiab ntau xyoo ntawm kev tshawb fawb qhia txog mutant KRAS ua tus tsav tsheb hauv nruab nrab ntawm cov qog nqaij hlav thiab kev kho mob, mutant KRAS yog lub hom phiaj tawv ncauj.
Ntau lub tswv yim tau sim txheeb xyuas cov molecules me me uas tsom KRAS, tab sis lawv tau ua rau muaj kev txwv tsis pub KRAS hauv hlwb. Qhov no tau txhawb cov kws sau ntawv los tsim ib qho kev sib txuas los txhim kho KRAS tshwj xeeb inhibitors, suav nrog kev hloov 2 hnab tshos (S-IIP) KRASG12C inhibitors uas khi rau thiab ua rau lub xeev GDP ntawm KRAS, ua rau nws nyob rau hauv qhov tsis sib haum xeeb.
Yuav kom ua tau zoo, tus inhibitor yuav tsum muaj lub zog siab thiab nrawm nrawm kinetics. Nws kuj yuav tsum muaj cov tshuaj pharmacokinetic zoo tshaj plaws kom tswj tau qhov raug thiab lub sijhawm ntev txaus los ntes GDP-kawg lub xeev tsis muaj zog ntawm KRAS ua rau lub voj voog nucleotide sai.
Cov kws tshawb nrhiav tau tsim thiab tsim cov ARS-1620 nrog cov khoom zoo li tshuaj, thiab txhim kho potency tshaj thawj tiam cov tebchaw. Kev ua tau zoo thiab kinetics hla cov kab ntawm tes nrog cov mutant allele raug soj ntsuam los txiav txim siab seb lub hom phiaj muaj nyob rau inhibit KRAS-GTP hauv cov qog puas txaus.
Inhibition ntawm kev loj hlob ntawm tes, nrog rau qhov muaj peev xwm ntawm cov tshuaj tiv thaiv tsis tshwj xeeb uas tuaj yeem qhia txog qhov muaj peev xwm rau toxicity, raug soj ntsuam.
Thaum kawg, txhawm rau ntsuas lub hom phiaj nyob hauv vivo, qhov ncauj ARS-1620 tau muab rau cov nas uas tsim cov qauv xenograft uas muaj KRAS p.G12C ua ib koob tshuaj ib zaug, lossis txhua hnub rau 5 hnub.
Cov kws tshawb nrhiav tau tshaj tawm tias ARS-1620 cuam tshuam cov qog nqaij hlav loj hlob nyob rau hauv ib koob- thiab lub sij hawm-raws li nrog cov cim qog regression.
Hauv tsib xenograft qauv ntawm NSCLC kab xov tooj ntawm tes hauv nas, txhua tus qauv tau teb tom qab ob mus rau peb lub lis piam ntawm kev kho mob, thiab plaub ntawm tsib tau nthuav tawm qhov tseem ceeb ntawm cov qog loj hlob. Tsis tas li ntawd, ARS-1620 tau txais txiaj ntsig zoo yam tsis muaj kev soj ntsuam toxicity thaum lub sijhawm kho.
"Ua ke, cov pov thawj hauv vivo uas ARS-1620 tau siv dav dav raws li ib tus neeg sawv cev thoob plaws NSCLC qauv muab pov thawj ntawm lub tswv yim tias ib feem tseem ceeb ntawm cov neeg mob p.G12C KRAS kev hloov pauv tuaj yeem tau txais txiaj ntsig los ntawm KRASG12C-qhia kev kho mob," hais cov sau phau ntawv.
Lawv tau hais ntxiv tias ARS-1620 yog KRASG12C ncaj qha molecule inhibitor uas muaj peev xwm, xaiv tau, hais lus bioavailable, thiab zam tau zoo.
Post lub sij hawm: May-22-2018