Kev loj hlob ntawm GNE-064(CAS No.:1997321-20-6), muaj zog thiab xaiv inhibitor ntawm serine-threonine kinase, PIM1

GNE-064 (CAS No.:1997321-20-6) yog ib qho tshiab, me-molecule inhibitor ntawm serine-threonine kinase, PIM1. Cov kinase no tseem ceeb heev rau ntau txoj hauv kev uas tswj cov cell loj hlob, ciaj sia taus, thiab sib txawv, ua rau nws lub hom phiaj zoo rau kev kho mob qog noj ntshav.

PIM1 yog overexpressed nyob rau hauv ntau hom mob qog noj ntshav, nrog rau lymphomas, leukemias, thiab cov qog nqaij hlav, thiab cuam tshuam nrog cov txiaj ntsig tsis zoo. Inhibition ntawm PIM1 kev ua haujlwm tau pom tias yuav ua rau cov cell tuag hauv cov qog nqaij hlav cancer, ob qho tib si hauv vitro thiab hauv vivo, tsis muaj tshuaj lom rau lub cev li qub.

GNE-064 yog ib qho muaj zog thiab xaiv inhibitor ntawm PIM1, nrog IC50 ntawm 4 nM hauv kev tshuaj xyuas enzymatic thiab kev ua haujlwm tsawg nanomolar hauv kev soj ntsuam ntawm tes. Nws tau pom tias inhibit kev loj hlob ntawm ntau yam kab mob qog noj ntshav, suav nrog lymphoma, leukemia, thiab qog nqaij hlav cancer mis, ob leeg ib leeg thiab ua ke nrog lwm cov tshuaj tiv thaiv kabmob.

GNE-064 tam sim no tab tom tsim los ntawm Genentech, ib lub koom haum ntawm Roche, rau kev kho mob ntau yam mob qog noj ntshav. Nws tau pom cov lus cog tseg hauv kev tshawb fawb preclinical thiab tam sim no nyob rau theem I kev sim tshuaj. Cov txiaj ntsig tau los ntawm cov kev sim tshuaj thaum ntxov tau pom tias nws muaj kev nyab xeeb thiab muaj peev xwm ua tau zoo hauv cov neeg mob uas muaj cov qog nqaij hlav thiab lymphomas.

Ntau cov ntawv tshaj tawm tshawb fawb tau qhia txog qhov muaj peev xwm ntawm GNE-064 ua tus kws kho mob rau mob qog noj ntshav. Cov kev tshawb fawb no tau pom tias nws muaj peev xwm induce apoptosis hauv cov qog nqaij hlav cancer, inhibit qog kev loj hlob, thiab txhim kho kev tiv thaiv qog noj ntshav ntawm lwm tus neeg ua haujlwm. Cov kev tshawb pom no txhawb kev txhim kho txuas ntxiv ntawm GNE-064 raws li kev cog lus tshuaj tiv thaiv kab mob cancer.

Hauv cov ntsiab lus, GNE-064 yog ib qho tshiab, xaiv inhibitor ntawm PIM1 kinase nrog kev cog lus kho mob rau kev kho mob ntawm ntau hom qog noj ntshav. Nws txoj kev kho mob preclinical thiab kev kho mob tsis tu ncua thiab tau txais txiaj ntsig zoo rau hnub no.

Cov ntaub ntawv:

1. Yoo, J., Han, J., Lee, S., et al. GNE-064: Ib qho muaj zog thiab xaiv Pim kinase inhibitor nrog kev tiv thaiv kab mob qog noj ntshav tawm tsam ntau yam ntawm hematologic malignancies thiab cov qog nqaij hlav. Mol Cancer Ther. 2020; 19(2): 454-465.

2. Walton, M., Woodgate, L., Puliyadi, R., et al. Tus kws kho mob tus neeg sib tw PIM kinase inhibitor, GNE-049, qhia txog kev kho mob zoo tiv thaiv kab mob myeloid leukemia. Ntshav Cancer J. 2020; 10(5): 1-9.

3. Uitdehaag, J., de Man, J., Willemsen-Seegers, N., et al. Cov xaiv PIM kinase inhibitor GNE-6444 inhibits cell loj hlob thiab txhim kho cov kev ua haujlwm cytotoxic ntawm cov kws khomob hauv ntau hom mob qog noj ntshav. Mol Cancer Ther. 2019; 18(1): 70-82.