@media na o le pupuni ma le (-Webkit-min-masini-pixel-ratio: 1.5), na o le pupuni ma le (-moz-min-device-pixel-ratio: 1.5), na o le screen ma le (-o-min-device-pixel -Ratio: 3/2), naʻo le lau ma le (min-masini-pixel-ratio: 1.5) {}
AASraw gaosia NMN ma NRC pauta tele!

Gefitinib

  1. Gefitinib Aotelega
  2. Gefitinib Faʻatinoga o gaioiga
  3. Gefitinib Faʻaaoga I le Lalolagi
  4. Aafiaga Itu o Gefitinib
  5. Teuina Gefitinib
  6. Sili atu Suʻesuʻega: "Lung Cancer Killer" Gefitinib

 

Gefitinib lagona

O le Gefitinib o se vailaʻau e taofia le kinase. O le igoa vailaʻau o le gefitinib o le 4-Quinazolinamine N- (3-chloro-4-fluorophenyl) -7-methoxy-6- [3- (4-morpholinyl) propoxy]. , o se vaega faʻatapulaʻa o vaega o le 22 daltons ma o se paʻu paepae lanu. Gefitinib o se maua fua faʻavae. O le molemole ei ai pKas o 24 ma 4. Gefitinib e mafai ona faʻauigaina ma le faʻaleagaina i le pH 3, ae o le mea e le mafai ai ona sosolo i luga atu o le pH 446.9, ma le solubility e faʻaititia lava i le va o le pH 5.4 ma le pH 7.2. i le pyridine, faʻavaʻa ona soluble i tetrahydrofuran, ma laʻititi soluble i methanol, ethanol (1%), ethyl acetate, propan-7-ol ma acetonitrile.

Gefitinib fualaʻau o loʻo avanoa e pei o enaena ata-ufiufi laulau, o loʻo iai le 250 mg o gefitinib paʻu, mo le tuʻuina atu o le tautala. O le aoga vaega o le laupapa laʻau o IRESSA fualaʻau o lactose monarchate, microcrystalline cellulose, croscarmellose sodium, povidone, sodium lauryl sulfate ma magnesium stearate. O le laupapa ufiufi o loʻo aofia ai le hypromellose, polyethylene glycol 300, titanium dioxide, red ferric oxide ma le samasama ferric oxide.

 

Faamatalaga Technical:

igoa Gefitinib
Igoa aloaia N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]-4-quinazolinamine
Numera CAS 184475-35-2
Synonyms ZD 1839
Faiga Faʻavae Molecular C22H24ClFN4O3
Fua Faatatau o le Umi 446.9
Mama Atoatoa i Tulaga ≥98%
Faʻatulagaga O se maa malosi
Solubility DMF: 20 mg / ml
DMSO: 20 mg / ml
DMSO: PBS (pH7.2) (1: 1): 0.5 mg / ml
Ethanol: 0.3 mg / ml
SMILES COC1=CC2=C(C(NC3=CC=C(F)C(Cl)=C3)=NC=N2)C=C1OCCCN4CCOCC4
InChi Code InChI=1S/C22H24ClFN4O3/c1-29-20-13-19-16(12-21(20)31-8-2-5-28-6-9-30-10-7-28)22(26-14-25-19)27-15-3-4-18(24)17(23)11-15/h3-4,11-14H,2,5-10H2,1H3,(H,25,26,27)
InChi Ki XGALLCVXEZPNRQ-UHFFFAOYSA-N
teuina o Meaai -20 ° C

 

Gefitinib o loʻo faʻaaogaina e togafitia ai le kanesa laiti o le sela sela ua sosolo i isi vaega o le tino i tagata ma nisi ituaiga o tuma. Gefitinib o loʻo iai i le vasega o vailaʻau e taʻua o le kinase inhibitors. E galue i le polokaina o le gaioiga o se mautinoa lava tupu mea e ono manaʻomia e fesoasoani kanesa sela faʻateleina.

AASraw o le polofesa gaosi o Gefitinib.

Faʻamolemole kiliki ii mo upusii faʻamatalaga: AvanoaFaʻafesoʻotaʻi matou

 

Gefitinib Faʻatinoga o gaioiga

O le Gefitinib o se mea e taofiofi ai le faʻatupulaia o le tupuolaola o le epidermal (EGFR) tyrosine kinase e fusifusia i le adenosine triphosphate (ATP) -ʻaʻa ai nofoaga o le enzyme. EGFR e masani ona faʻaalia e soʻona faʻailoa mai i nisi sela o tagata kanesa o le tino, pei o le mama ma le fatafata sela o le kanesa. O le soona faʻamalamalamaina e tau atu ai i le faʻalauteleina o le faʻagaoioia o le anti-apoptotic Ras signal transduction cascades, ma mulimuli ane mafua ai le faʻateleina o le ola o sela kanesa ma le le taofiofia sela faʻateleina. Gefitinib o le muamua filifilia filifilia o le EGFR tyrosine kinase lea e taua foi o Her1 poʻo ErbB-1. E ala i le taofia o le EGFR tyrosine kinase, o le faʻailo o le faʻasologa o cascades o loʻo taofia foi, ma mafua ai ona taofia le faʻateleina o sela leaga.

 

Gefitinib Faʻaaoga I le Lalolagi

Gefitinib o loʻo faʻatau atu nei ile sili atu ile 64 atunuʻu. Gefitinib na faʻamaonia ma maketi mai ia Iulai 2002 i Iapani, ma avea ai ma atunuʻu muamua na faʻaulufale mai le vailaʻau.

le Ua faamaonia e le FDA le gefitinib I le Me 2003 mo le kanesa o le sela e le o laʻititi (NSCLC). Na faʻamaonia e avea ma monotherapy mo togafitiga o tagata mamaʻi ma le NSCLC faʻasolosolo i le lotoifale pe faʻasolosolo i le maeʻa ai o le platinum-based ma le docetaxel chemotherapies, o se togafitiga lona tolu.

Ia Iuni 2005 na aveʻese e le FDA le faʻamaoniga mo le faʻaaogaina i tagata mamaʻi fou ona o le le lava o faʻamaoniga na faʻateleina ai le ola.

I totonu o Europa gefitinib o loʻo faʻailoa mai talu mai le 2009 ile NSCLC alualu i luma i laina uma o togafitiga mo tagata mamaʻi o loʻo teu fesuiaʻiga EGFR. O lenei igoa na faʻatagaina ina ua maeʻa gefitinib faʻaalia o se muamua-laina togafitiga e faʻaleleia atili alualu ai i luma-leai se ola vs. a platinum faʻalua pulega i tagata mamaʻi teuina na suiga. IPASS na muamua o le fa vaega III faʻataʻitaʻiga na faʻamaoniaina le sili atu gefitinib i lenei tagata gasegase faitau aofaʻi.

I le tele o isi atunuʻu o loʻo maketi ai nei gefitinib ua faʻamaonia mo tagata mamaʻi ua iai le NSCLC maualuluga na mauaina le tusa o le tasi muamua le chemotherapy pulega. Peitai, o talosaga e faʻalauteleina lona igoa o se laina muamua togafitiga i tagata mamaʻi teuina EGFR fesuiaʻiga o loʻo faʻagasolo nei i le faʻavae faʻavae luga o sili ona lata mai faʻasaienisi molimau. EGFR fesuiaiga mo naive i le lotoifale alualu i luma pe metastatic, le mafaamatalaina NSCLC. O lenei faʻatupeina faʻalauaʻitele mo le amataga 2012-masina vaitaimi ma faʻafouina pe a leai se alualu i luma. I Iulai 4, 13, le FDA faʻamaonia gefitinib o se muamua-laina togafitiga mo NSCLC.

Gefitinib

Aafiaga Itu o Gefitinib

Mea taua e manatua e uiga i le itu aʻafiaga o gefitinib:

♦ O le tele o tagata e le o aʻafia i aʻafiaga uma na lisiina.

♦ O aʻafiaga e masani ona vaʻaia i tulaga o lo latou amataga ma le umi.

♦ O aʻafiaga e toeititi lava suia i taimi uma ma o le a alu ese pe a maeʻa togafitiga.

♦ E tele filifiliga e fesoasoani ai i le faʻaititia poʻo le puipuia o aʻafiaga.

♦ E leai se sootaga i le va o le i ai po o le ogaoga o aʻafiaga ma le aoga o vailaʻau.

 

O mea nei o aʻafiaga e masani (tupu i sili atu nai lo 30%) mo tagata mamaʻi aveina gefitinib:

♦ Manava

♦ Paʻu tali (mageso, fuafua)

AASraw o le polofesa gaosi o Gefitinib.

Faʻamolemole kiliki ii mo upusii faʻamatalaga: AvanoaFaʻafesoʻotaʻi matou

 

O nei aʻafiaga e le masani masani aʻafiaga (tupu i tusa o le 10-29%) o tagata mamaʻi mauaina gefitinib:

♦ Faanoi

♦ Talosaga

♦ mageso

♦ Leai se manaʻoga

♦ Faasoesa mata

 

E seasea tupu ni mataupu (tusa o le 1%) o se itu ogaoga o le gasegase o le mama i le tumutumu (niumonia, poʻo le fulafula o mama e aunoa ma se siama). Ina ua tupu lenei itu aafiaga, sa masani ona o faatasi ma manava faigata ma tale po o se maualalo togi fiva manaʻomia falemai. 1/3 o mataupu na mafua ai le oti. A faʻafuaseʻi ona amata mai le pupuu o le manava, tale ma / poʻo le fiva e tupu a o inuina le gefitinib, faʻailoa i lau fomaʻi polofesa.

O le siʻitia o le ate ile faʻataʻitaʻiga (transaminase, bilirubin, ma alkaline phosphatase) na maitauina i tagata mamaʻi na togafitia ma le gefitinib. O nei tulaga maualuluga e leʻi o faʻatasi mai ma ni faʻailoga o le oona o le ate. Peitaʻi, e mafai e lau polofesa tausi soifua ona siaki le suʻega ile toto e siaki ai lou ate i taimi uma, a o e inu i le gefitinib.

E le o aʻafiaga uma e lisi atu i luga. Nisi e seasea (tupu i lalo ifo o le 10% o tagata mamaʻi) e le o lisiina iinei. Peitaʻi, e tatau ona e faʻailoa i taimi uma lau auaunaga faʻasoifua maloloina pe a fai e te maua se faʻailoga e le masani ai.

 

Gefitinib teuina o Meaai

Taofi le gefitinib i totonu o le koneteina na sau i totonu, tapunia mau, ma mai le aapa atu o tamaiti. Teu ia i le vevela potu ma alu ese mai le sili atu vevela ma susu (le i totonu o le faletaele).

E le manaʻomia gefitinib tatau ona tiaʻi i ni auala faʻapitoa e mautinoa ai e le mafai ona faʻaumatia ia fagafao, tamaiti, ma isi tagata. Ae ui i lea, oe le tatau ona fufuluina lenei gefitinib lalo o le faletaele. Nai lo lena, o le auala sili ona lelei e tiaʻi ai lau gefitinib e ala i se vailaʻau toe faʻafoʻi polokalama. Talanoa i lau fomaʻi faʻafomaʻi pe faʻafesoʻotaʻi lau matagaluega o lapisi / toefaʻaoga e te aʻoaʻo ai e uiga i le toe ave i tua o polokalame i lou nuʻu. Vaai i le Lafoaʻiga saogalemu a le FDA uepisaite o vailaʻau mo nisi faʻamatalaga pe a fai e te le maua se avanoa i se polokalama toe faʻafoʻi.

E taua le taofi uma o vailaau mai le vaai ma aapa atu i tamaiti le tele o koneteina (e pei o mafaufauga i vaiaso taʻitasi ma i latou e tilotilo mata, kulimi, patches, ma inhalers) e le o tamaiti e puipuia ma e mafai e tamaiti laiti ona tatala faigofie. Mo le puipuia o tamaiti laiti mai le 'ona oona, ia tapuni pea le pulou saogalemu ma vave tuu le vailaau i se nofoaga saogalemu - o se tasi o loʻo agai i luga ma mamao ese mai o latou mata ma aapa atu.

Gefitinib

Sili atu Suʻesuʻega: "Lung Cancer Killer" Gefitinib

Gefitinib o se tala faʻatatau togafitiga e taofiofia ai le tyrosine kinase gaioiga o le epidermal tuputupu ae mea taliaina e ala i le tauvaga poloka le ATP noatia nofoaga. I suesuega muamua gefitinib ua faʻaalia ai le malosi gaioiga i le tele o tumo faʻataʻitaʻiga, e aofia ai le tele o kanesa kanesa sela sela ma xenografts. Lua lapoʻa randomized Phase II suʻesuʻega (IDEAL 1 ma IDEAL 2) i pretreated leai-laʻititi sela kanesa kanesa lipotia se tali tali latalata atu i le 20% i laina laina lua ma ∼10% ia i latou na faʻafoligaina ma lua pe sili atu togafitiga chemotherapy. O le ola feololo i nei suesuega e lua latalata i le 6-8 masina. I le avea ai o se muamua-laina togafitiga, gefitinib ua iloiloina i le tuʻufaʻatasia ma lua eseese chemotherapy regimens i lua tele randomized suesuega (INTACT 1 ma INTACT 2). O suʻesuʻega uma e lua ua le faʻaalia se alualu i luma i le ola i luga o le aofaʻi o tagata mamaʻi accrual o> 1000 tagata mamaʻi i suʻesuʻega taʻitasi. O isi itu mulimuli (eg, taimi i le alualu i luma ma tali fua faatatau) e leʻi faʻaleleia atili e le faʻaopopoina o gefitinib. O loʻo faʻaalia mai suʻesuʻega suʻesuʻega e iloilo ai le sao o le gefitinib ile tausiga o tagata mamaʻi na mauaina le chemotherapy poʻo le chemoradiotherapy. Suesuega suʻesuʻe gefitinib o muamua-laina monotherapy e manaʻomia foi.

Ole toʻatele o tagata mamaʻi e leai se laʻititi sela kanesa o le mama (NSCLC) mulimuli ane atiaʻe metastatic faʻamaʻi poʻo faʻamaʻi e le taliaina i le lotoifale togafitiga faʻapitoa ma e ono avea ma sui tauva mo faiga togafitiga. E ui lava e mafai e le chemotherapy ona faʻaleleia le ola i tagata mamaʻi ma gasegase maualuluga, o le avanoa e na o le months2 masina nai lo le fesoasoani sili ona lelei, ma o le mea lea e mafua ai le tele o aʻafiaga. O le sailiga mo soʻo fou e sili atu le malosi e pei o chemotherapy ae sili atu faʻapalepaleina o le sili ona taua. O numera o tala fou e faʻapitoa ona faʻasaga i filifiliga filifilia o loʻo iai kanesa sela, e pei o le epidermal tuputupu ae mea taliaina (EGFR), o loʻo faʻataʻitaʻia i le alualu i luma NSCLC. E oʻo mai i le taimi nei, o tagata mamaʻi lava na maua le gasegase o le NSCLC ua maeʻa ona suʻesuʻeina, ae o loʻo i ai le mafuaaga lelei e suʻesuʻe ai le tele o nei sooupu i faʻamaʻi na muamua atu, o loʻo i ai foʻi nisi o faʻafitauli masani o gafa.

EGFR o loʻo faʻaalia tele i ituaiga eseese o maʻa tuma, e aofia ai le NSCLC. EGFR o loʻo faʻaalia tele i le tele (∼80%) o le sela sela o sela sela, ma le tusa o le afa o uma mama adenocarcinomas ma sela sela tetele. Faʻagaoioia o le EGFR i kanesa sela ua faʻaalia e faʻalauteleina ai gaioiga e aofia ai i le faʻatupulaia sela sela, angiogenesis, osofaʻiga, ma metastasis, ma e taofia apoptosis. EGFR (erbB1 poʻo HER1) o se sui o le erbB receptor aiga, lea e aofia ai foi erbB2 (HER2), erbB3 (HER3), ma le erbB4 (HER4). O le transmembrane glycoprotein e aofia ai le extracellular ligand-binding domain, o le transmembrane domain, ma le intracellular signal-transducing domain ma le tyrosine kinase gaoioiga. A maeʻa fusifusia o se physiological ligand pei o epidermal tuputupu aʻe mafuaʻaga, le EGFR dimerates ma seisi EGFR monomer poʻo se isi tagata o le erbB aiga. O lenei mea e tau atu ai i le faʻagaoioia o le tyrosine kinase, o le autofosforilasi o le tyrosine, ma le amataina o faʻailoaina o le cascades ma iʻu ai i le tele o tali atu i lalo e pei o le faʻatele o sela. E le gata i lea, o le faʻaalia o le EGFR i tumors na fesoʻotaʻi ma le le lelei le tali atu i togafitiga, faʻalauteleina o le teteʻe i vailaʻau o le cytotoxic, faʻasolosolo o faʻamaʻi, ma le ola lelei. O isi auala o le faʻateleina o le faʻailo o le EGFR e ono aʻafia i le faʻatupulaia o sela o le tuma e aofia ai le faʻateleina o le liʻo o le extracellular, o le heterodimerization o le EGFR, ma le suiga o le EGFR. O le ituaiga taatele o mutated EGFR i tumors o EGFRvIII, lea e maua i le oʻo atu i le 39% o NSCLC mataupu. O le EGFRvIII o loʻo aveeseina se suiga o suiga mai amino acid 6 i le 273 i le extracellular fusifusia o loʻo iai ma faʻaalia ai le faʻavaeina o le tyrosine kinase gaioiga e tutoʻatasi mai le fusifusia o le liʻo faʻapitoa.

AASraw o le polofesa gaosi o Gefitinib.

Faʻamolemole kiliki ii mo upusii faʻamatalaga: AvanoaFaʻafesoʻotaʻi matou

 

Tusitaiala

[1] Rukazenkov Y, Tautalaga G, Marshall G, et al. Epidermal tuputupu aʻe vaega receptor tyrosine kinase taofiofia: tutusa ae eseese? Vailaau Anticancer 2009; 20: 856-866.

[2] Woodburn JR O le epidermal tuputupu ae mea taliaina ma lona taofiofia i kanesa togafitiga. Pharmacol Ther 1999; 82: 241–250.

[3] Le-laʻitiiti Laʻau Laʻau Kanesa Galulue Faatasi Chemotherapy i le le laʻititi sela kanesa kanesa: o se meta-auiliiliga faʻaaoga faʻafouina faʻamatalaga luga tagata taʻitoʻatasi gasegase mai 52 randomized togafitiga faʻafomaʻi. BMJ 1995; 311: 899–909.

[4] Douillard JY, Kim ES, Hirsh V, et al. Gefitinib (IRESSA) faʻatusatusa i le docetaxel i tagata mamaʻi ma le maua i le lotoifale e leai se laʻititi sela kanesa o le kanesa na muamua togafitia ma platinum-faʻavae chemotherapy: o se randomized, tatala-igoa vaega III suʻesuʻega (INTEREST). J Thoracic Oncol 2007; 2: PRS-02–

[5] Fukuoka M, Wu Y, Thongprasert S, et al. Biomarker suʻesuʻeina mai le vaega III, faʻasolosolo, matala-faʻailoga, laina muamua o le gefitinib (G) ma le carboplatin / paclitaxel (C / P) i tagata gasegase filifilia (pts) ma alualu i luma le laiti tamai sela kanesa (NSCLC) i Asia (IPASS). J Clin Oncol 2009; 27 Faʻaopopo. 15: 8006–.

[6] Reck MA tele laʻasaga agai i togafitiga faʻapitoa o kanesa kanesa ma le gefitinib: o le IPASS faʻataʻitaʻiga ma tala atu. Tomai Rev Anticancer Ther 2010; 10: 955–965.

[7] Barker, AJ Suesuega e tau atu i le faailoagofieina o le ZD1839 (IRESSA): o se tautala gaioiga, filifilia epidermal tuputupu ae vaega taliaina receptor tyrosine kinase taofiofia fuafua i le togafitiga o kanesa. Bioorg. Med. Chem. Lett 11, 1911–1914 (2001).

[8] Wakeling, AE et al. ZD1839 (Iressa): o se tautala gaioiga taofiofia o epidermal tuputupu ae mea faʻailo ma gafatia mo kanesa togafitiga. Kanesa Res. 62, 5749-5754 (2002).

[9] Yarden, Y. & Sliwkowski, MX Untangling le ErbB signaling network. Natura Rev. Mol. Sela Biol. 2, 127–137 (2001).

[10] Cersosimo, RJ Kanesa kanesa: o se toe iloiloga. Am. J. Soifua Maloloina Syst. Fale Talavai 59, 611–642 (2002).

0 fiafia
Manatu 170

E mafai ona e fiafia foi

ua tapunia faamatalaga.