AASraw tsim NMN thiab NRC hmoov hauv qhov ntau!

Neratinib

Neratinib yog ib qho muaj zog, tsis muaj kev hloov pauv tyrosine kinase inhibitor (TKI) ntawm HER1, HER2, thiab HER4, thiab tam sim no tab tom tsim kho. Neratinib irreversibly khi rau qhov kev cuam tshuam kev cuam tshuam cov paib ntawm HER1, HER2, HER3, thiab epithelial kev loj hlob tau txais, thiab inhibits phosphorylation thiab ob peb HER nqes los cuam tshuam cov hauv kev. Qhov tshwm sim yog txo qis loj hlob thiab nce cell tuag ntau dua. Cov kev tshawb fawb pom tau tias qhov mob siab ntawm HER taw los ntawm neratinib yog txoj hauv kev zoo dua ntawm kev tua HER-mediated qog kev loj hlob thiab kov yeej cov qog kev khiav tawm ntawm cov kev paub txog cov tshuaj HER2-tam sim no thiab cov tshuaj kho mob.

Hauj lwm yam khoom

Cov yam ntxwv yooj yim

khoom npe Neratinib
CAS Number 698387-09-6
molecular Formula C30H29ClN6O3
Mis Lub Cev 557.04
Synonyms HKI-272;

PB272;

Neratinib;

Nerlynx;

698387-09-6.

tsos Tawm-dawb kom lub teeb daj hmoov
Cia thiab Ua Haujlwm Qhuav, tsaus thiab nyob rau hauv 0 - 4 C rau lub sij hawm luv (hnub mus rau lub lis piam) lossis -20 C rau lub sij hawm ntev (hli txog xyoo).

 

Neratinib Piav Qhia

Neratinib, tseem hu ua HKI-272 lossis PB272, yog qhov ncauj tawm, tsis muaj kev cuam tshuam kev tiv thaiv ntawm HER-2 receptor tyrosine kinase nrog cov kev muaj peev xwm antineoplastic.

Neratinib khi rau HER-2 receptor irreversibly, txo qis autophosphorylation hauv hlwb, pom tseeb los ntawm kev hom phiaj cysteine ​​seem hauv ATP-khi hnab tshos ntawm receptor.

Kev kho mob ntawm cov hlwb nrog tus neeg sawv cev no ua rau muaj kev cuam tshuam ntawm cov dej hauv qab cov teeb meem thiab cov kev sib hloov ntawm tes mus los; raug ntes ntawm G1-S (Ntxhoo 1 / DNA synthesis) -paug kev hloov ntawm lub voj voog faib tawm ntawm tes; thiab thaum kawg txo cellular proliferation.

Neratinib tseem ua rau cov kab mob loj zuj zus (EGFR) kinase thiab ua kom loj hlob ntawm EGFR-ua kom cov hlwb.

 

Neratinib Kev Txom Nyem ntawm Kev Ua

Neratinib yog ib qho muaj zog, tsis muaj kev hloov pauv tyrosine kinase inhibitor (TKI) ntawm HER1, HER2, thiab HER4, thiab tam sim no tab tom tsim kho. Neratinib irreversibly khi rau qhov kev cuam tshuam kev cuam tshuam cov paib ntawm HER1, HER2, HER3, thiab epithelial kev loj hlob tau txais, thiab inhibits phosphorylation thiab ob peb HER nqes los cuam tshuam cov hauv kev. Qhov tshwm sim yog txo qis loj hlob thiab nce cell tuag ntau dua. Cov kev tshawb fawb pom tau tias qhov mob siab ntawm HER taw los ntawm neratinib yog txoj hauv kev zoo dua ntawm kev tua HER-mediated qog kev loj hlob thiab kov yeej cov qog kev khiav tawm ntawm cov kev paub txog cov tshuaj HER2-tam sim no thiab cov tshuaj kho mob.

Neratinib kuj tau ua pov thawj tias qhov ua tau zoo rau kev kho thawj HER2-zoo, metastatic cancer mis (MBC). Thaum siv los ua ke nrog paclitaxel, neratinib pom ib qho ORR ntawm 73%. Thaum muab sib xyaw nrog capecitabine, lwm tus neeg sawv cev rau tshuaj lom neeg, ORR yog 63%. Ntxiv rau HER2-zoo MBC, neratinib kuj tseem muaj txiaj ntsig hauv cov neeg mob uas muaj HER2-mutated mob cancer mis. Hauv theem 2 kev sim SUMMIT, cov neeg mob uas muaj HER2-mutated mob cancer mis muaj 33% ORR ntawm 8 lub lis piam.

Neratinib yog thawj TKI ua pov thawj los txo qis kev pheej hmoo rau kev mob rov qab rau cov neeg mob uas muaj HER2-mob cancer mis thaum ntxov. Raws li qhov ua tau zoo ntawm neratinib nyob rau thaum ntxov-HER2-zoo mob cancer mis, MBC, thiab HER2-mutant hlav, neratinib yog xav tias yuav dhau los ua tus qauv tshiab rau kev saib xyuas nyob rau ntau qhov chaw kho mob cancer mis.

 

Neratinib Thov

Neratinib khi rau HER-2 receptor irreversibly, txo qis autophosphorylation hauv hlwb, pom tseeb los ntawm kev hom phiaj cysteine ​​seem hauv ATP-khi hnab tshos ntawm receptor.

HER2-lub mis mob cancer mis ua kom ntau dhau ntawm HER2 protein. HER2 protein tso rau saum npoo ntawm cov qog nqaij hlav cancer thiab txais cov cim qhia uas qhia tias mob qog nqaij hlav loj thiab loj tuaj. Neratinib tawm tsam HER2-zoo mob cancer mis los ntawm kev thaiv cov qog nqaij hlav cancer kev muaj peev xwm txais cov cim qhia kev loj hlob.

Neratinib yog lub hom phiaj kho, tab sis tsis zoo li Herceptin (lub npe tshuaj: trastuzumab), Kadcyla (lub npe tshuaj: T-DM1 lossis ado-trastuzumab emtansine), thiab Perjeta (tshuaj lub npe: pertuzumab), nws tsis yog qhov kev tiv thaiv kab mob. Kev siv tshuaj tiv thaiv kab mob yog cov qauv ntawm cov tshuaj tiv thaiv kab mob uas ua haujlwm zoo li cov tshuaj tiv thaiv ua los ntawm peb lub cev tsis muaj zog. Neratinib yog tshuaj lom neeg lub cev, tsis muaj tshuaj tiv thaiv.

 

Neratinib Sab Nyab Los & Ceeb Toom

Neratinib tuaj yeem ua rau mob tuag taus mob hauv qee cov neeg thiab mob me me mus rau mob raws plab yuav luag txhua tus neeg; cov neeg uas noj nws kuj tseem muaj feem yuav ua kom mob raws plab zoo li lub cev qhuav dej thiab roj tsis xws ntshav.

Zoo sib xws nws muaj qhov pheej hmoo mob siab mob siab thiab ntau tus neeg mob muaj qee theem ntawm nws; Cov tsos mob ntawm daim siab puas tsuaj nrog rau kev nkees, xeev siab, ntuav, txoj cai sab saud mob lossis mob rhiab, kub taub hau, tawm pob, thiab qib siab ntawm eosinophils.

Ntxiv rau cov saum toj no, ntau dua 10% ntawm cov neeg noj nws muaj xeev siab, mob plab, ntuav, mob rau ntawm lawv daim di ncauj, mob plab, tsis qab los noj mov, tawm pob, thiab mob pob txha.

 

reference

[1] Xuhong JC, Qi XW, Zhang Y, Jiang J. Mechanism, kev nyab xeeb thiab kev ua tau zoo ntawm peb tyrosine kinase inhibitors lapatinib, neratinib thiab pyrotinib hauv HER2-zoo mob cancer mis. Am J Cancer Res. 2019 Oct 1; 9 (10): 2103-2119. eCollection 2019. Rov Los Saib. PubMed PMID: 31720077; PubMed Central PMCID: PMC6834479.

[2] LiverTox: Kev Soj Ntsuam thiab Tshawb Xyuas Ntaub Ntawv ntawm Kev Tshuaj Ntsuam Ntsej Muag Mob Siab Hauv Is Taws Nem [Is Taws Nem]. Bethesda (MD): Lub Koom Haum Tebchaws ntawm Kev Mob ntshav qab zib thiab lub plab thiab lub raum; 2012-. Muaj los ntawm http://www.ncbi.nlm.nih.gov/books/NBK548937/ PubMed PMID: 31644242.

[3] Lub rooj muag zaub LA, Roberts JL, Dent P. Lub luag haujlwm ntawm tes taw qhia rau ntawm kab hla ntawm autophagy thiab apoptosis hauv txoj cai kev mob qog cell ciaj sia nyob hauv kev teb rau sorafenib thiab neratinib. Semin Cancer Biol. 2019 Oct 20. pii: S1044-579X (19) 30024-0. doi: 10.1016 / j.semcancer.2019.10.013. [Epub ua ntej sau] Tshawb xyuas. PubMed PMID: 31644944.

[4] Mais J, Dawb Y. Neratinib rau Kev Kho Mob Thaum Ntxov HER2-Zoo Mob Cancer Mis. J Adv Xyaum On On. 2018 Nov-Dec; 9 (7): 750-754. Epub 2018 Nov 1. Rov Los Saib. PubMed PMID: 31249722; PubMed Central PMCID: PMC6570523.

[5] Collins DM, Conlon NT, Kannan S, Verma CS, Eli LD, Lalani AS, Yas J. Preclinical Cov Cwj Pwm ntawm Irreversible Pan-HER Kinase Inhibitor Neratinib Piv nrog Lapatinib: Qhov cuam tshuam rau kev kho mob HER2-Zoo thiab HER2- Kev Hloov Ua Tus Mob Cancer Mis. Khees Xaws (Basel). 2019 Tsib Hlis 28; 11 (6). pii: E737. doi: 10.3390 / cancers11060737. Ntsuam Xyuas. PubMed PMID: 31141894; PubMed Central PMCID: PMC6628314.

[6] Deeks ED. Neratinib: Kev Pom Zoo Hauv Ntiaj Teb Thawj Zaug. Tshuaj. 2017 Lub Kaum Hli; 77 (15): 1695-1704. doi: 10.1007 / s40265-017-0811-4. Ntsuam Xyuas. PubMed PMID: 28884417.

[7] Kourie HR, El Rassy E, Clatot F, de Azambuja E, Lambertini M. Tawm kev kho mob HER2-zoo thaum ntxov mob cancer mis: tsom rau neratinib. Onco Lub Hom Phiaj Ther. 2017 Jul 10; 10: 3363-3372. doi: 10.2147 / OTT.S122397. eCollection 2017. Kev Ntsuam Xyuas. PubMed PMID: 28744140; PubMed Central PMCID: PMC5513878.

[8] “Cov lus txhais ntawm neratinib - National Cancer Institute Phau Ntawv Txhais Lus”. Txais 1 Lub Kaum Ob Hlis 2008.

[9] “Daim ntawv qhia cov ntsiav tshuaj Neratinib” (PDF). Tsoom Fwv Tebchaws Asmeskas Khoom Noj thiab Tshuaj (FDA). Lub Xya Hli 2017. Khaws Cia 6 Lub Ob Hlis 2018. Rau daim ntawv qhia hloov tshiab pom, FDA nplooj ntawv nplooj ntawv rau NDA 208051 Cov kab lus no suav nrog cov ntawv sau los ntawm cov peev txheej no, uas yog nyob rau hauv qhov chaw pej xeem. Gandhi L, li al. (2017). "MA04.02 Neratinib ± Temsirolimus hauv HER2-mutant ntsws mob qog nqaij hlav: thoob ntiaj teb, kev tshawb nrhiav theem II." Phau ntawv Journal Thoracic Oncology. 12 (1): S358-9. doi: 10.1016 / j.jtho.2016.11.398.