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Gefitinib

  1. Ukubuka konke kweGefitinib
  2. Indlela yeGefitinib yesenzo
  3. Ukusetshenziswa kweGefitinib Emhlabeni
  4. Imiphumela emibi ye-Gefitinib
  5. Isitoreji seGefitinib
  6. More Rearch: "Umbulali Womdlavuza Wamaphaphu" Gefitinib

 

Gefitinib Uhlolojikelele

Igama lamakhemikhali le-gefitinib lingu-4-Quinazolinamine N- (3-chloro-4-fluorophenyl) -7-methoxy-6- [3- (4-morpholinyl) propoxy]. IGefitinib ine-molecular formula C22H24ClFN4O3 , isisindo samangqamuzana esihlobo sama-dalton angama-446.9 futhi siyimpuphu enemibala emhlophe. IGefitinib iyisisekelo samahhala. I-molecule ine-pKas ka-5.4 no-7.2. IGefitinib ingachazwa njengoncibilikayo kancane ku-pH 1, kepha cishe ayincibiliki ngaphezu kwe-pH 7, lapho ukuncibilika kwehla kakhulu phakathi kwe-pH 4 ne-pH 6. Kumakhemikhali awanyakazisa amanzi, i-gefitinib incibilika ngokukhululeka ku-glacial acetic acid kanye ne-dimethyl sulfoxide, encibilikayo ku-pyridine, kuncibilika kancane ku-tetrahydrofuran, futhi kuncibilike kancane ku-methanol, i-ethanol (99.5%), i-ethyl acetate, i-propan-2-ol ne-acetonitrile.

Amaphilisi e-Gefitinib ayatholakala njengamaphilisi ansundu aqoshwe ngefilimu, aqukethe ama-250 mg we gefitinib powder, yokuphatha ngomlomo. Izithako ezingasebenzi zomgogodla wethebhulethi wamathebulethi e-IRESSA yi-lactose monohydrate, microcrystalline cellulose, i-croscarmellose sodium, i-povidone, i-sodium lauryl sulfate ne-magnesium stearate. Ukumbozwa kwethebhulethi kwenziwa nge-hypromellose, i-polyethylene glycol 300, i-titanium dioxide, i-red ferric oxide ne-yellow ferric oxide.

 

Ulwazi Technical:

Igama Gefitinib
Igama elihlelekile N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]-4-quinazolinamine
CAS Inombolo 184475-35-2
omqondofana ZD 1839
Formula Yamamolekhula C22H24ClFN4O3
Isisindo sesisindo 446.9
Ukuhlanzeka ≥98%
Ukubunjwa I-crystalline iqinile
solubility I-DMF: 20 mg / ml
I-DMSO: 20 mg / ml
I-DMSO: I-PBS (pH7.2) (1: 1): 0.5 mg / ml
I-Ethanol: 0.3 mg / ml
SMILES COC1=CC2=C(C(NC3=CC=C(F)C(Cl)=C3)=NC=N2)C=C1OCCCN4CCOCC4
Ikhodi yeChi 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)
Ukhiye we-InChi Ingxenye #: XGALLCVXEZPNRQ-UHFFFAOYSA-N
Storage -20 ° C

 

I-Gefitinib isetshenziselwa ukwelapha umdlavuza wamaphaphu weseli ongeyona omncane osabalalele kwezinye izingxenye zomzimba kubantu abanezinhlobo ezithile zamathumba. UGefitinib usesigabeni semithi ebizwa nge-kinase inhibitors. Isebenza ngokuvimba isenzo sento ethile eyenzeka ngokwemvelo engadingeka ukusiza umdlavuza amaseli ayanda.

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Gefitinib Inqubo yesenzo

IGefitinib iyisithibeli se-epidermal growth factor receptor (EGFR) tyrosine kinase ebopha indawo ebopha i-adenosine triphosphate (ATP) ye-enzyme. I-EGFR ivame ukukhonjiswa ukuthi icindezelwe ngokweqile kumaseli athile e-carcinoma, njengephaphu nesifuba amangqamuzana omdlavuza. I-Overexpression iholela ekusebenzeni okuthuthukile kwamakhasethi wokudluliswa kwesiginali we-anti-apoptotic Ras, ngemuva kwalokho okuholele ekusindeni okwandayo kwamaseli womdlavuza nokwanda kwamaseli okungalawulwa. IGefitinib iyona inhibitor yokuqala yokukhetha ye-EGFR tyrosine kinase nayo ebizwa nge-Her1 noma i-ErbB-1. Ngokuvimbela i-EGFR tyrosine kinase, amakhasethi asayinayo esezansi nawo ayavinjelwa, okuholele ekwandeni kwamangqamuzana amabi.

 

Gefitinib Sebenzisa Emhlabeni

IGefitinib okwamanje ithengiswa emazweni angaphezu kwama-64. IGefitinib yamukelwa yathengiswa kusukela ngoJulayi 2002 eJapan, okwenza kwaba yizwe lokuqala ukungenisa lo muthi.

The I-FDA ivume i-gefitinib ngoMeyi 2003 ngomdlavuza wamangqamuzana ongewona omncane (i-NSCLC). Kwavunywa njenge-monotherapy ekwelapheni iziguli ezine-NSCLC esithuthuke kakhulu endaweni noma ngemuva kokuhluleka kwamakhemikhali e-platinum-based kanye ne-docetaxel chemotherapies, njengokwelashwa komugqa wesithathu.

NgoJuni 2005 i-FDA yahoxisa imvume yokusetshenziswa ezigulini ezintsha ngenxa yokushoda kobufakazi bokuthi yelula impilo.

E-Europe i-gefitinib ikhonjiswa kusukela ngo-2009 ku-NSCLC esezingeni eliphezulu kuyo yonke imigqa yokwelashwa kweziguli ezigcina ukuguquka kwezinguquko e-EGFR. Leli lebula linikezwe ngemuva kokuthi i-gefitinib ikhombise njengokwelashwa komugqa wokuqala ukuthuthukisa kakhulu ukuqhubeka kokuqhubeka ngaphandle kokuqhubekela phambili kuqhathaniswa nombuso ophindwe kabili weplatinamu ezigulini ezigcina ukuguquka okunjalo. I-IPASS ibilokhu kungukuqala kokuhlolwa kwesigaba III kokuqinisekisa ukuphakama kwe-gefitinib kulesi siguli.

Kwamanye amazwe amaningi lapho i-gefitinib idayiswa khona njengamanje kuvunyelwe iziguli ezine-NSCLC esezingeni eliphakeme ezazithole okungenani umbuso owodwa wamakhemikhali wangaphambilini. Kodwa-ke, izicelo zokunwebisa ilebuli yayo njengokwelashwa komugqa wokuqala ezigulini ezigcina ukuguquka kwezakhi ze-EGFR okwamanje kusacutshungulwa kususelwa ebufakazini besayensi bamuva. Ukuguqulwa kwe-EGFR kwe-NSCLC engenamqondo ethuthukile endaweni yangakini noma ye-metastatic. Lokhu kukhokhelwa esidlangalaleni isikhathi sokuqala sezinyanga ezi-2012 nokuvuselelwa uma kungekho ukuqhubeka. NgoJulayi 4, 13, i-FDA yavuma i-gefitinib njengokwelashwa komugqa wokuqala kwe-NSCLC.

Gefitinib

Imiphumela emibi ye Gefitinib

Izinto ezibalulekile okufanele uzikhumbule ngemiphumela emibi ye-gefitinib:

♦ Abantu abaningi abayitholi yonke imiphumela emibi ebaluliwe.

Imiphumela emibi ivame ukubikezelwa ngokuqala kwayo nobude bayo.

Effects Imiphumela engemihle ivame ukubuyiselwa emuva futhi izophela ngemuva kokuphela kokwelashwa.

Are Kunezinketho eziningi zokusiza ukunciphisa noma ukuvimbela imiphumela emibi.

♦ Abukho ubudlelwano phakathi kobukhona noma ukuqina kwemiphumela emibi nokusebenza komuthi.

 

Imiphumela emibi elandelayo ivamile (yenzeka ngaphezu kwama-30%) ezigulini ezithatha i-gefitinib:

♦ Uhudo

Ukusabela kwesikhumba (ukuqubuka, induna)

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Le miphumela emibi yimiphumela emibi ejwayelekile (eyenzeka cishe nge-10-29%) yeziguli ezithola i-gefitinib:

Isicanucanu

♦ Ukuhlanza

Ching Ukulunywa

♦ Isifiso esibi sokudla

Ukucasuka kweso

 

Amacala angavamile (cishe u-1%) womphumela obucayi wesifo samaphaphu (i-pneumonia, noma ukuvuvukala kwamaphaphu ngaphandle kokutheleleka). Lapho kwenzeka lo mphumela oseceleni, bekuvame ukuhambisana nobunzima bokuphefumula ngokukhwehlela noma ngemfiva esezingeni eliphansi edinga ukulaliswa esibhedlela. I-1/3 yamacala iholele ekufeni. Uma ukuqala kokuphefumula okungazelelwe, ukukhwehlela kanye / noma umkhuhlane kwenzeka ngenkathi uthatha i-gefitinib, yazisa uchwepheshe wakho wokunakekelwa kwezempilo.

Ukuphakama kokuhlolwa kokusebenza kwesibindi (i-transaminase, i-bilirubin, ne-alkaline phosphatase) kuye kwabonwa ezigulini ezelashwa nge-gefitinib. Lokhu kuphakama bekungahambisani nanoma yiziphi izimpawu zobuthi besibindi. Kodwa-ke, uchwepheshe wakho wezokunakekelwa kwempilo angahlola ukuhlolwa kwegazi ukuqapha ukusebenza kwesibindi sakho ngezikhathi ezithile, ngenkathi uthatha i-gefitinib.

Akuyona yonke imiphumela emibi ebhalwe ngenhla. Ezinye ezingavamile (ezenzeka ezigulini ezingaphansi kuka-10%) azikho ohlwini lapha. Kodwa-ke, kufanele njalo wazise umhlinzeki wakho wezokunakekelwa kwezempilo uma uhlangabezana nezimpawu ezingavamile.

 

Gefitinib Storage

Gcina i-gefitinib esitsheni efike ngayo, ivalwe ngokuqinile, futhi lapho izingane zingafinyeleleki khona. Yigcine ekamelweni lokushisa futhi kude nokushisa okweqile nomswakama (hhayi endlini yangasese).

I-gefitinib engadingeki kufanele ilahlwe ngezindlela ezikhethekile zokuqinisekisa ukuthi izilwane ezifuywayo, izingane, nabanye abantu abakwazi ukuzidla. Kodwa-ke, akufanele ukhiphe le gefitinib phansi kwendlu yangasese. Esikhundleni salokho, indlela engcono kakhulu yokulahla i-gefitinib yakho ngohlelo lokubuyisa umuthi. Khuluma nosokhemisi wakho noma uthinte umnyango wangakini wokulahla udoti / wokusebenzisa kabusha ukuze ufunde ngezinhlelo zokubuyisela emuva emphakathini wakho. Bona i- Ukulahlwa Ngokuphepha Kwemithi kwe-FDA ukuthola eminye imininingwane uma ungakwazi ukufinyelela kuhlelo lokubuyisa.

Kubalulekile ukugcina zonke izidakamizwa zingaboni futhi zifinyelele ezinganeni iziqukathi eziningi (njengezimpilisi zamasonto onke kanye nalawo amaconsi amaso, ama-creams, ama-patches, nama-inhalers) akuzona izingane ezingamelana nazo futhi izingane ezincane zingazivula kalula. Ukuze uvikele izingane ezincane ebuchosini, zihlale zikhiya izinhlamvu zokuphepha futhi zibeke ngokushesha imithi endaweni ephephile - ephezulu futhi ephuma futhi engaboni futhi efinyelele.

Gefitinib

More Rearch: "Umbulali Womdlavuza Wamaphaphu" Gefitinib

IGefitinib iyindlela yokwelashwa ebhekiswe enoveli evimbela umsebenzi we-tyrosine kinase we-epidermal growth factor receptor ngokuvimbela ngokuncintisana indawo ebopha i-ATP. Ezifundweni ezandulela ukwelashwa i-gefitinib ikhombise umsebenzi onamandla kumamodeli amaningi wesimila, kufaka phakathi imigqa eminingana yomdlavuza wamaphaphu kanye nama-xenografts. Izifundo ezimbili ezinkulu ezingahleliwe zeSigaba II (IDEAL 1 ne-IDEAL 2) kumdlavuza wamaphaphu wamangqamuzana ongeyona amancane owenziwe ngaphambi kwesikhathi wabika izinga lokuphendula elisondela kuma-20% ezigulini zomugqa wesibili kanye no-%10% kulabo ababelethwe ngemithi emibili noma ngaphezulu yamakhemikhali. Ukusinda okumaphakathi kulezi zifundo ezimbili kusondele ezinyangeni eziyi-6-8. Njengokwelashwa komugqa wokuqala, i-gefitinib ihlolwe ngokuhlanganiswa nezinhlobo ezimbili ezihlukene ze-chemotherapy ezifundweni ezimbili ezinkulu ezenziwa ngokungahleliwe (INTACT 1 ne-INTACT 2). Zombili lezi zifundo zehlulekile ukukhombisa ukuthuthuka kokusinda ekuqoqeni okuphelele kweziguli> zeziguli eziyi-1000 esifundweni ngasinye. Amanye amaphuzu wokugcina (isb. Isikhathi sokuqhubeka nezinga lokuphendula) nawo awathuthukiswanga ngokufakwa kwe-gefitinib. Izifundo ezingeziwe zikhonjisiwe ukuhlola iqhaza elingaba khona le-gefitinib ekunakekelweni kweziguli ezithola i-chemotherapy noma i-chemoradiotherapy. Izifundo eziphenya i-gefitinib njenge-lineotherapy yokuqala iyadingeka.

Iningi leziguli ezinamaseli angewona amancane umdlavuza wamaphaphu (I-NSCLC) ekugcineni iba nesifo se-metastatic noma isifo esingatholakali ekwelashweni kwasendaweni kuphela futhi okungaba ngabaqokelwe izindlela zokwelashwa ezihlelekile. Yize ukwelashwa ngamakhemikhali kungathuthukisa ukusinda ezigulini ezinesifo esithuthukile, inzuzo kuphela izinyanga ezingama-∼2 ngaphezu kokunakekelwa okungcono kakhulu kokusekelwa, futhi lokhu kubiza imiphumela emibi kakhulu. Ukufunwa kwama-ejenti amasha okungenani asebenza njenge-chemotherapy kepha okubekezelelwa kangcono kubaluleke kakhulu. Amanxusa amaningana amanoveli asebenza ngokukhethekile ngokumelene nokuqondiwe okukhethiwe okukhona umdlavuza amaseli, njenge-epidermal growth factor receptor (EGFR), ayahlolwa ku-NSCLC ethuthukile. Kuze kube manje, ikakhulukazi iziguli ezine-NSCLC esezingeni eliphakeme sezihloliwe, kepha kunengqondo enhle yokuphenya amaningana ala ma-ejenti kuzilungiselelo zezifo zangaphambili, lapho okunye ukungajwayelekile kofuzo okubhekiswe kukho sekuvele kukhona.

I-EGFR ivezwa kakhulu ezinhlobonhlobo zamathumba aqinile, kufaka ne-NSCLC. I-EGFR ivezwa kakhulu kuningi (∼80%) lamaphaphu ama-squamous cell carcinomas, futhi cishe uhhafu wawo wonke ama-lung adenocarcinomas nama-carcinomas amakhulu. Ukuqaliswa kwe-EGFR kumaseli womdlavuza kukhonjisiwe ukukhuthaza izinqubo ezibandakanyeka ekwandeni kweseli le-tumor, i-angiogenesis, ukuhlasela, ne-metastasis, kanye nokuvimbela i-apoptosis. I-EGFR (erbB1 noma i-HER1) iyilungu lomndeni we-erbB receptor, okubandakanya ne-erbB2 (HER2), erbB3 (HER3), ne-erbB4 (HER4). I-transmembrane glycoprotein eyakhiwe ngesizinda se-ligand-binding extracellular, isizinda se-transmembrane, kanye ne-intracellular signal-transducing domain enomsebenzi we-tyrosine kinase. Ngemuva kokubopha i-ligand yomzimba efana ne-epidermal factor factor, i-EGFR iyancipha ngenye i-monomer ye-EGFR noma elinye ilungu lomndeni we-erbB. Lokhu kuholela ekusetshenzisweni kwe-tyrosine kinase, i-autophosphorylation ye-tyrosine, kanye nokuqaliswa kokufaka uphawu kumakhasethi agcina ngokuholela ezimpendweni ezahlukahlukene ezisezansi ezifana nokwanda kweseli. Ngaphezu kwalokho, ukubonakaliswa kwe-EGFR kumathumba kuhlotshaniswe nempendulo engeyinhle ekwelashweni, ukuthuthukiswa kokumelana nomuthi we-cytotoxic, ukuqhubeka kwezifo, nokusinda okuncane. Ezinye izindlela zokwandisa ukusayinda kwe-EGFR okungabandakanyeka ekwandeni kweseli lesisu kufaka amazinga akhuphukile we-ligand yangaphandle, i-heterodimerization ye-EGFR, nokuguqulwa kwe-EGFR. Uhlobo oluvame kakhulu lwe-EGFR eguquliwe emathunjini yi-EGFRvIII, etholakala kumacala angama-39% wamacala e-NSCLC. I-EGFRvIII ithwala ukususwa kokushintshwa kusuka kuma-amino acid 6 kuye ku-273 kusizinda sokubopha esingaphandle kwamaseli futhi kukhombisa umsebenzi we-tyrosine kinase ozimele ngaphandle kwe-ligand extrusion yamaseli.

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Izikhombo

[1] URukazenkov Y, Speake G, Marshall G, et al. I-Epidermal growth factor receptor tyrosine kinase inhibitors: iyafana kodwa yehlukile? Izidakamizwa ze-Anticancer 2009; 20: 856-866.

[2] I-Woodburn JR I-epidermal growth factor receptor kanye nokuvinjelwa kwayo ekwelashweni komdlavuza. I-Pharmacol Ther 1999; 82: 241–250.

[3] Iqembu Elisebenzisana Nomdlavuza Wamaseli Omncane. I-Chemotherapy kumdlavuza wamaphaphu weseli ongeyona omncane: ukuhlaziywa kwe-meta kusetshenziswa idatha ebuyekeziwe ezigulini ngazinye kusuka ezivivinyweni zomtholampilo ezingama-52. BMJ 1995; 311: 899-909.

[4] UDouillard JY, uKim ES, uHirsh V, et al. I-Gefitinib (IRESSA) kuqhathaniswa ne-docetaxel ezigulini ezinomdlavuza wamaphaphu wesifo samangqamuzana ongaphakeme noma ophansi owelashwa ngaphambilini nge-chemotherapy esekwe eplatinamu: isifundo esingahleliwe, esinelebuli evulekile yesigaba III (INZALO). UJ Thoracic Oncol 2007; 2: PRS-02–

[5] UFukuoka M, Wu Y, Thongprasert S, et al. I-Biomarker ihlaziya i-phase III, i-randomised, ilebula evulekile, ucwaningo lokuqala lwe-gefitinib (G) kuqhathaniswa ne-carboplatin / paclitaxel (C / P) ezigulini ezikhethwe ngokwelashwa (pts) ezinomdlavuza ongeyena omncane wesifo somdlavuza wamaphaphu (NSCLC) ku I-Asia (IPASS). J Umtholampilo Oncol 2009; 27 Isikhwama. 15: 8006–.

[6] I-Reck MA isinyathelo esikhulu ekwelapheni komuntu ngamunye komdlavuza wamaphaphu nge-gefitinib: isivivinyo se-IPASS nangaphezulu. Isazi Rev Anticancer Ther 2010; 10: 955-965.

[7] I-Barker, i-AJ Study eholela ekuhlonzweni kwe-ZD1839 (IRESSA): i-epidermal growth factor factor receptor tyrosine kinase inhibitor ebhekiswe ekwelapheni umdlavuza. I-Bioorg. IMed. I-Chem. I-Lett. 11, 1911-1914 (2001).

[8] Wakeling, AE et al. I-ZD1839 (Iressa): i-inhibitor ngomlomo esebenzayo ye-epidermal factor factor ekhombisa amandla okwelashwa komdlavuza. Umdlavuza Res. 62, 5749-5754 (2002).

[9] I-Yarden, Y. & Sliwkowski, MX Ukuxhuma inethiwekhi yokukhombisa i-ErbB. Imvelo uMfu Mol. Iseli Biol. 2, 127-137 (2001).

[10] Cersosimo, RJ umdlavuza wamaphaphu: ukubuyekeza. Am. J. Impilo Syst. Isidakamizwa. 59, 611-642 (2002).

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