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Neratinib

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Neratinib o se malosi, le mafai ona toe faʻafouina tyrosine kinase inhibitor (TKI) o HER1, HER2, ma HER4, ma o loʻo galueina nei. Neratinib e le mafai ona toe fusia i le faʻailoga o laina o le HER1, HER2, HER3, ma le epithelial tuputupu ae vaega, ma taofia ai le phosphorylation ma le tele o HER auala faʻailo i lalo. O le iʻuga ua faʻaititia le faʻaolaola ma ua atili tele ai le oti o sela. O suʻesuʻega faʻafomaʻi na faʻaalia ai o le taofiofia o le HER i luga ole faʻailo e ala i le neratinib o se auala sili atu ona aoga e taofi ai le tuputupu aʻe o le HER-faʻafesoʻotaʻi ma le faʻafetaiaia o le sosola ese o le tuma i auala ua masani ai ma togafitiga o loʻo faʻatautaia nei e le HER2 ma sui o le chemotherapeutic.

Faamatalaga oloa

Tulaga Autu

Igoa oloa Neratinib
Numera CAS 698387-09-6
Faiga Faʻavae Molecular C30H29ClN6O3
Fua Faatatau o le Umi 557.04
Synonyms HKI-272;

PB272;

Neratinib;

Nerlynx;

698387-09-6.

Faʻaaliga Paʻepaʻe-paʻepaʻe i le samasama samasama pauta
Teuina ma Taulimaina Faʻamago, pogisa ma i le 0 - 4 C mo se taimi puʻupuʻu (aso i vaiaso) poʻo le -20 C mo se taimi umi (masina i tausaga).

 

Neratinib Faʻamatalaga

Neratinib, e faʻaigoa foʻi ia HKI-272 poʻo le PB272, o se tagata faʻaaoga tuʻu saʻo, e le mafai ona toe faʻafitia le HER-2 receptor tyrosine kinase ma le ono antineoplastic gaioiga.

Neratinib fusifusia i le HER-2 talimalo e le mafai ona suia, ma faʻaititia ai le autophosporylasi i sela, e foliga mai i le faʻatutuina o se cystine toe i le ATP-fusifusia taga o le receptor.

Togafitiga o sela ma lenei sooupu e mafua ai le taofiofia o gaioiga o gaioiga faʻasolosolo o gaioiga faʻasolosolo ma sela taʻamilosaga faʻatonutonu auala; pueina i le G1-S (Gap 1 / DNA synthesis) -faʻasologa suiga o le sela vaevaega taʻamilosaga; ma iʻu ai ina faʻaititia le faʻaolaolaina o sela.

Neratinib taofia foi le epidermal tuputupu ae mea taliaina (EGFR) kinase ma le faʻateleina o EGFR-faʻalagolago sela.

 

Neratinib Faiga o Gaioiga

Neratinib o se malosi, le mafai ona toe faʻafouina tyrosine kinase inhibitor (TKI) o HER1, HER2, ma HER4, ma o loʻo galueina nei. Neratinib e le mafai ona toe fusia i le faʻailoga o laina o le HER1, HER2, HER3, ma le epithelial tuputupu ae vaega, ma taofia ai le phosphorylation ma le tele o HER auala faʻailo i lalo. O le iʻuga ua faʻaititia le faʻaolaola ma ua atili tele ai le oti o sela. O suʻesuʻega faʻafomaʻi na faʻaalia ai o le taofiofia o le HER i luga ole faʻailo e ala i le neratinib o se auala sili atu ona aoga e taofi ai le tuputupu aʻe o le HER-faʻafesoʻotaʻi ma le faʻafetaiaia o le sosola ese o le tuma i auala ua masani ai ma togafitiga o loʻo faʻatautaia nei e le HER2 ma sui o le chemotherapeutic.

Neratinib ua faʻamaonia foi le aoga i le laina muamua togafitiga o HER2-lelei, metastatic susu kanesa (MBC). A faʻaaoga faʻatasi ma paclitaxel, ua faʻaalia e le neratinib le ORR e 73%. A tuʻufaʻatasia ma capecitabine, o leisi chemotherapeutic agents, o le ORR e 63%. I se faʻaopopoga i le HER2-positive MBC, sa aoga tele foʻi le neratinib i tagata mamaʻi ma le kanesa ole susu o le HER2-mutated. I le vaega 2 SUMMIT faʻataʻitaʻiga, o tagata mamaʻi na maua i le kanesa o le susu ua HER2-mutated na maua le 33% ORR i le 8 vaiaso.

Neratinib o le muamua TKI faʻamaonia e faʻaititia le lamatiaga mo faʻamaʻi toe tupu i tagata mamaʻi i le amataga-HER2-lelei kanesa o le susu. Faʻavae i luga o le aoga o neratinib i le amataga-laasaga HER2-lelei kanesa o le susu, MBC, ma HER2-mutant tumors, neratinib o loʻo faʻamoemoeina e avea ma fou tulaga o le tausiga i le tele o susu susu togafitiga togafitiga.

 

Neratinib Talosaga

Neratinib fusifusia i le HER-2 talimalo e le mafai ona suia, ma faʻaititia ai le autophosporylasi i sela, e foliga mai i le faʻatutuina o se cystine toe i le ATP-fusifusia taga o le receptor.

HER2-lelei susu kanesa faia tele o le HER2 polotini. O le HER2 protein e nofo i luga o sela o le kanesa ma maua faʻailoga e taʻu ai le kanesa e tupu ma salalau. Neratinib fusuʻaga HER2-lelei kanesa o le susu e ala i le poloka o sela kanesa 'mafai ona maua tuputupu aʻe faʻailoga.

Neratinib o se faʻataʻitaʻia togafitiga, ae le pei o Herceptin (igoa vailaʻau: trastuzumab), Kadcyla (igoa vailaʻau: T-DM1 poʻo ado-trastuzumab emtansine), ma Perjeta (igoa vailaʻau: pertuzumab), e le o se puipuia faʻamoemoeina togafitiga. Ole togafiti faʻapitoa e faʻataʻitaʻia togafitiga o faʻaupuga ia o vailaʻau e masani ona tutupu e pei o meaola niniʻi na faia e le tatou tino puipuia. Neratinib o se vailaʻau oona, ae le o se vailaʻau.

 

Neratinib Itu Aafiaga & Lapataiga

Neratinib mafai mafua ai le manaʻomia manava tatā i nisi tagata ma agamalu i feololo manava tatā i le toetoe lava o tagata uma; O tagata na te aveina ma lamatiaga foi mo faʻalavelave o le manava tata e pei o le faʻamateina ma le le paleni o le eletise.

E faʻapena foi ona iai se aʻafiaga o le leaga o le ate ma le tele o tagata mamaʻi e i ai ni tulaga o ia; faʻailoga o le ate afaina e aofia ai le lelava, niniva, puaʻi, taumatau luga quadrant tiga poʻo le agavaivai, fiva, mageso, ma maualuga tulaga o eosinophils.

I se faʻaopopoga i mea o loʻo taua i luga, e ova atu ma le 10% o tagata o loʻo tago e tiga, tiga o le manava, puaʻi, papala i luga o latou laugutu, tiga le manava, faʻaititia le manaʻo, mageso, ma maso maso.

 

Tusitaiala

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[2] LiverTox: Fomaʻi ma Faʻamatalaga Suesuega e uiga i Vailaʻau-Faʻaosoina Manua o le ate [Initaneti]. Bethesda (MD): National Institute of Diabetes ma Digestive ma Fatugaʻo faʻamaʻi; 2012-. Avanoa mai http://www.ncbi.nlm.nih.gov/books/NBK548937/ PubMed PMID: 31644242.

[3] Booth LA, Roberts JL, Dent P. O le matafaioi a sela faailo i le crosstalk i le va autophagy ma apoptosis i le tulafono faatonutonu o le olaola sela sela i le tali atu i sorafenib ma neratinib. Semin Kanesa Biol. 2019 Oketopa 20. pii: S1044-579X (19) 30024-0. fai: 10.1016 / j.semcancer.2019.10.013. [Epub luma atu o le lolomi] Toe iloiloga. PubMed PMID: 31644944.

[4] Miles J, White Y. Neratinib mo le Togafitiga o le Early-Stage HER2-Positive Breast Cancer. J Adv Faʻapitoa Oncol. 2018 Nov-Tes; 9 (7): 750-754. Epub 2018 Nov 1. Iloilo. PubMed PMID: 31249722; PubMed Central PMCID: PMC6570523.

[5] Collins DM, Conlon NT, Kannan S, Verma CS, Eli LD, Lalani AS, Crown J. Preclinical Characteristics o le Irreversible Pan-HER Kinase Inhibitor Neratinib Faʻatusatusa ma Lapatinib: Aafiaga mo le Togafitiga o HER2-Positive ma HER2- Kanesa o le susu ua suia. Le faʻamaʻa (Basel). 2019 Me 28; 11 (6). pii: E737. faia: 10.3390 / kanesa11060737. Iloiloga PubMed PMID: 31141894; PubMed Central PMCID: PMC6628314.

[6] Deeks ED. Neratinib: Muamua Faʻamaonia i le Lalolagi. Fualaʻau. 2017 Oketopa; 77 (15): 1695-1704. faia: 10.1007 / s40265-017-0811-4. Iloiloga PubMed PMID: 28884417.

[7] Kourie HR, El Rassy E, Clatot F, de Azambuja E, Lambertini M. Faʻalauiloa togafitiga mo HER2-lelei amataga laʻasaga kanesa o le susu: taulaʻi i neratinib. Onco Manulauti Ther. 2017 Jul 10; 10: 3363-3372. faia: 10.2147 / OTT.S122397. eCollection 2017. Iloilo. PubMed PMID: 28744140; PubMed Central PMCID: PMC5513878.

[8] "Faʻauigaina o neratinib - National Cancer Institute Drug Guide". Toe aumai 1 Tesema 2008.

[9] "Neratinib tablets igoa" (PDF). US Food and Drug Administration (FDA). Iulai 2017. Toe aumai ile 6 Fepuari 2018. Mo faʻailoga faʻafouina vaʻai, itulau faasino igoa a le FDA mo NDA 208051 O lenei tusitusiga o loʻo tuʻufaʻatasia ai tusitusiga mai lenei punaoa, o loʻo i totonu o le lautele lautele. Gandhi L, et al. (2017). "MA04.02 Neratinib ± Temsirolimus i HER2-mutant mama kanesa: o se faavaomalo, randomized vaega II suesuega". Tusi o tala o le Thoracic Oncology. 12 (1): S358-9. fai: 10.1016 / j.jtho.2016.11.398.