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Gefitinib

  1. Nlekọta Gefitinib
  2. Usoro Gefitinib nke ime ihe
  3. Gefitinib Jiri N'ime Worldwa
  4. Mmetụta Gefitinib
  5. Nchekwa Gefitinib
  6. Rearch ọzọ: "Ọrịa cancer na-egbu egbu" Gefitinib

 

Gefitinib Overview

Gefitinib bụ onye na-egbochi kinase.The aha kemịkal nke gefitinib bụ 4-Quinazolinamine N- (3-chloro-4-fluorophenyl) -7-methoxy-6- [3- (4-morpholinyl) propoxy] .Gefitinib nwere usoro molekul C22H24ClFN4O3 , Ngwunye ngwugwu metụtara nke 446.9 dalton na ọ bụ ntụ na-acha ọcha. Gefitinib bụ ntọala n'efu. Molekul nwere pKas nke 5.4 na 7.2. Enwere ike ịkọwa Gefitinib dị ka ihe nwere ike ịgbakwunye na pH 1, mana ọ bụ ihe anaghị agbasasị karịa pH 7, na solubility na-agbada ngwa ngwa n'etiti pH 4 na pH 6. N'ime ihe mgbaze ndị na-abụghị mmiri, gefitinib bụ soluble kpamkpam na glaica acetic na dimethyl sulfoxide, soluble na pyridine, na-agbachapụtụ na tetrahydrofuran, na ntakịrị soluble na methanol, ethanol (99.5%), ethyl acetate, propan-2-ol na acetonitrile.

Mbadamba Gefitinib dị ka mbadamba ihe nkiri na-acha aja aja, nke nwere 250 mg nke gefitinib powder, maka nchịkwa ọnụ. Ihe na-adịghị arụ ọrụ nke mbadamba nkume nke mbadamba IRESSA bụ lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, povidone, sodium lauryl sulfate na magnesium stearate. Ihe mkpuchi mbadamba nkume bụ hypromellose, polyethylene glycol 300, titanium dioxide, red ferric oxide and yellow ferric oxide.

 

Nka na ụzụ Ozi:

aha Gefitinib
Aha aha N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(4-morpholinyl)propoxy]-4-quinazolinamine
CAS Number 184475-35-2
Synonyms ZD 1839
molekụla Formula C22H24ClFN4O3
Ụdị Ụdị 446.9
ọcha ≥98%
Nwa A crystalline siri ike
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
Usoro InChi 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 Igodo XGALLCVXEZPNRQ-UHFFFAOYSA-N
nchekwa -20 ° C

 

A na-eji Gefitinib agwọ ọrịa kansa mkpụrụ akụ na-abụghị obere nke gbasaa n'akụkụ ndị ọzọ n'ahụ mmadụ nwere ụdị etuto ahụ. Gefitinib nọ na klas nke ọgwụ a na-akpọ ndị na-emechi kinase. Ọ na-arụ ọrụ site na igbochi ihe nke ụfọdụ ihe na-apụtaghị ìhè nwere ike ịdị mkpa iji nyere aka cancer mkpụrụ ndụ na-amụba.

 

Gefitinib Nhazi ihe

Gefitinib bụ onye na-egbochi ihe na-akpata epidermal growth factor (EGFR) tyrosine kinase nke na-ejikọta na adenosine triphosphate (ATP) -nke njikọ nke enzyme. A na-egosikarị EGFR na ụfọdụ mkpụrụ ndụ carcinoma mmadụ, dịka akpa ume na ara sel cancer. Nkọwapụta na-eduga n'ịmegharị arụmọrụ nke mgbochi apoptotic Ras signal transduction cascades, na-esote na-eme ka ndụ nke mkpụrụ ndụ kansa na ụba na-enweghị nchịkwa na-amụba. Gefitinib bụ onye nchịkwa nhọrọ izizi nke EGFR tyrosine kinase nke a na-akpọkwa Her1 ma ọ bụ ErbB-1. Site na igbochi EGFR tyrosine kinase, a na-egbochikwa cascades na-egosi ala, na-ebute mmụba cell na-adịghị mma.

 

Gefitinib Jiri Na Worldwa

A na-ere Gefitinib ugbu a na mba 64. A kwadoro Gefitinib ma wepụta ya na July 2002 na Japan, na-eme ka ọ bụrụ mba mbụ mbubata ọgwụ ahụ.

The FDA kwadoro gefitinib na Mee 2003 maka ọrịa cancer akwara na-abụghị obere (NSCLC) .A kwadoro ya ka ọ bụrụ ọgwụgwọ maka ọgwụgwọ nke ndị ọrịa nwere NSCLC dị elu na mpaghara ma ọ bụrụ na ọdịda nke ọgwụ platinum na docetaxel chemotherapies dị ka usoro ọgwụgwọ nke atọ.

Na June 2005, FDA wepụrụ nkwado maka iji ndị ọrịa ọhụrụ n'ihi enweghị ihe akaebe na ọ gbatịpụrụ ndụ.

Na Europe, a na-egosi gefitinib ebe ọ bụ na 2009 ka NSCLC dị elu na usoro ọgwụgwọ niile maka ndị ọrịa na-ebugharị mgbanwe EGFR. Edere aha a mgbe gefitinib gosipụtara dị ka usoro ọgwụgwọ mbụ iji meziwanye ọganihu na-enweghị ọganihu na usoro ọchịchị okpukpu abụọ nke ndị ọrịa na-ebu ụdị mmụba ahụ. IPASS bụ nke mbụ n'ime usoro nke atọ nke ule atọ iji gosipụta ịdị elu gefitinib na ndị ọrịa a.

N'ọtụtụ mba ndị ọzọ ebe a na-ere gefitinib ugbu a, a kwadoro ya maka ndị ọrịa nwere NSCLC dị elu ndị natara opekata mpe otu usoro ọgwụ chemotherapy gara aga. Otú ọ dị, ngwa iji gbasaa aha ya dị ka usoro ọgwụgwọ mbụ na ndị ọrịa na-ebugharị mgbanwe EGFR bụ nke dị ugbu a na-adabere na ihe mmụta sayensị kachasị ọhụrụ. [See okwu] Dị ka August 2012 New Zealand kwadoro gefitinib dị ka usoro ọgwụgwọ mbụ maka ndị ọrịa Mgbanwe EGFR maka onye agụta agam n’ihu ma ọ bụ metastatic, nke a na-enweghị ike ịkọwapụta NSCLC. A kwadoro nke a n'ihu ọha maka oge ọnwa 4 na mmeghari ohuru ma ọ bụrụ na enweghị ọganihu. Na July 13, 2015, FDA kwadoro gefitinib dị ka usoro ọgwụgwọ mbụ maka NSCLC.

Gefitinib

Mmetụta nke Gefitinib

Ihe ndị dị mkpa icheta banyere mmetụta dị n'akụkụ nke gefitinib:

Ọtụtụ ndị anaghị enweta mmetụta niile edepụtara.

Effects A na-ahụkarị mmetụta ndị dị na mmalite nke oge ha na oge ha.

Effects Mmetụta ndị na-adịkarị na-agbanwe agbanwe mgbe niile ma ọ ga-apụ mgbe emesịrị ọgwụgwọ.

Enwere ọtụtụ nhọrọ iji nyere aka belata ma ọ bụ gbochie mmetụta ndị ọzọ.

Enweghị mmekọrịta dị n'etiti ọnụnọ ma ọ bụ ogo nke mmetụta ndị ọzọ na ịdị irè nke ọgwụ ahụ.

 

Mmetụta ndị a na-esokarị (na-eme karịa 30%) maka ndị ọrịa na-anabata gefitinib:

Afọ ọsịsa

Reaction Mmeghachi omume anụ ahụ (ọkụ ọkụ, ihe otutu)

 

Mmetụta ndị a bụ mmetụta na-adịkarịghị (na-eme n'ihe dị ka 10-29%) nke ndị ọrịa na-anata gefitinib:

♦ Nausea

♦ Akpịrị

Oko

Appet Agụụ adịghị mma

Irrit Anya mgbakasị

 

Ọnọdụ ndị na-adịghị ahụkebe (ihe dị ka 1%) nke oke nsonaazụ nke ọrịa akpa ume (pneumonia, ma ọ bụ mbufụt nke ngụgụ na-enweghị ọrịa) Mgbe mmetụta a mere, ọ na - esokarị nsogbu iku ume na ụkwara ma ọ bụ ahụ ọkụ dị ala na - achọ ụlọ ọgwụ. 1/3 nke ikpe ebutewo ọnwụ. Ọ bụrụ na mbido iku ume, ụkwara na / ma ọ bụ ahụ ọkụ na mberede na-eme mgbe ị na-aga gefitinib, gwa ndị ọkachamara ahụike gị.

Achọpụtala elu na nyocha ọrụ imeju (transaminase, bilirubin, na alkaline phosphatase) na ndị ọrịa na-agwọ gefitinib. Ejighị ihe mgbaàmà ọ bụla nke nsị nke imeju na-esonyere ugwu ndị a. Agbanyeghị, ọkachamara ahụike gị nwere ike ịlele nyocha ọbara iji nyochaa ọrụ imeju gị oge ụfọdụ, mgbe ị na-ewere gefitinib.

E depụtaghị mmetụta niile dị n'akụkụ. Edepụtaghị ụfọdụ ndị dị obere (na-eme ihe na-erughị 10% nke ndị ọrịa) ebe a. Otú ọ dị, ị ga-agwa ndị na-elekọta ahụike gị mgbe niile ma ọ bụrụ na ị nwere ihe mgbaàmà ọ bụla pụrụ iche.

 

Gefitinib nchekwa

Debe gefitinib n'ime akpa ọ batara, mechie nke ọma, ma erute ụmụaka aka. Chekwaa ya na ime ụlọ ma pụọ ​​na oke okpomọkụ na mmiri (ọ bụghị n'ime ime ụlọ ịwụ).

Ekwesiri gefitinib na-ekwupụtaghị ya n'ụzọ pụrụ iche iji hụ na anụ ụlọ, ụmụaka, na ndị ọzọ enweghị ike iri ha. Agbanyeghị, ịkwesighi iwepụ gefitinib a n'ụlọ mposi. Kama, ụzọ kachasị mma iji tụfuo gefitinib bụ site na mmemme nnabata ọgwụ. Gwa onye dibia ogwu gi ma obu kpoturu ndi na eme ka mkpofu ahihia nke obodo gi ka imuta ihe omumu nke ime obodo. Lee Ihe mkpofu Ahụike nke FDA na weebụsaịtị maka ozi ndị ọzọ ma ọ bụrụ na ịnweghị ohere ịnweta usoro mmeghachị.

Ọ dị mkpa ka ị ghara ịchọta ọgwụ niile ma hụ ụmụaka dị ka ọtụtụ nchịkọta (dịka ntụrụndụ kwa izu na ndị na-ahụ anya, creams, patches, and inhalers) abụghị ụmụaka na-eguzogide ma ụmụaka nwere ike imeghe ha ngwa ngwa. Iji kpuchido ụmụntakịrị site na nsị, mechie mkpọchi nchebe ozugbo tinye ọgwụ ahụ na ebe nchekwa - nke dị elu ma pụọ ​​ma n'anya ha.

Gefitinib

Rearch ọzọ: "Ọrịa cancer na-egbu egbu" Gefitinib

Gefitinib bụ akwụkwọ akụkọ ezubere iche nke na-egbochi ọrụ tyrosine kinase nke ihe nnabata epidermal site na iji asọmpi na-egbochi saịtị njikọ ATP. Na nyocha nke emere gefitinib egosiputa ihe di ike na otutu otutu nke otutu, tinyere otutu uzo ogwu cancer na xenografts. Nnukwu usoro ọmụmụ II nke abụọ (IDEAL 1 na IDEAL 2) na-emeghị ka ọ bụrụ obere cancer cancer na-akọ akụkọ nzaghachi na-abịaru 20% na ndị ọrịa nke abụọ na ∼10% na ndị a na-eji usoro ọgwụ chemotherapy abụọ ma ọ bụ karịa. Ogologo etiti n'etiti ọmụmụ ihe abụọ a ruru ọnwa 6-8. Dị ka usoro ọgwụgwọ nke mbụ, a tụlere gefitinib yana yana usoro ọgwụgwọ chemotherapy abụọ dị iche iche na nnukwu ọmụmụ abụọ enweghị usoro (INTACT 1 na INTACT 2). Nnyocha abụọ ahụ egosighi mmụba na nlanarị na ọnụọgụ ọrịa nke> ndị ọrịa 1000 n'ọmụmụ ihe ọ bụla. Ihe njedebe ndị ọzọ (dịka, oge iji na-aga n'ihu na ọnụego nzaghachi) emeghịkwa ka mma site na mgbakwunye nke gefitinib. A na-egosiputa ihe omumu ndi ozo iji nyochaa oru nke gefitinib na mmezi nke ndi oria ndi natara chemotherapy ma obu chemoradiotherapy. Nnyocha na-enyocha gefitinib dị ka usoro ọgwụgwọ mbụ na-achọkwa.

Imirikiti ndị ọrịa nwere obere cell kansa cancer (NSCLC) mechara mepụta ọrịa metastatic ma ọ bụ ọrịa nke na-anaghị anabata naanị ọgwụgwọ mpaghara ma bụrụ ndị nwere ike ịnwe usoro ọgwụgwọ. Ọ bụ ezie na ọgwụgwọ ọgwụ nwere ike melite lanarị na ndị ọrịa nwere ọrịa dị elu, uru a bụ naanị months2 ọnwa karịa nlekọta nkwado kachasị mma, nke a na-akwụkwa nnukwu ọghọm. Ọchịchọ maka ndị ọrụ ọhụụ nke opekata mpe dị ka kemotherapy mana anabatago nke ọma bụ nke kachasị mkpa. A ọnụ ọgụgụ nke akwụkwọ akụkọ na-eme kpọmkwem megide họrọ zaa ugbu a cancer a na - anwale mkpụrụ ndụ, dịka onye na - anabata ihe na - eto eto epidermal (EGFR) na NSCLC dị elu. Ruo ugbu a, a chọpụtala ndị ọrịa nwere NSCLC dị elu, mana enwere ezi uche iji chọpụta ọtụtụ n'ime ndị ọrụ a na ntọala ọrịa ndị mbụ, ebe ụfọdụ ihe na-arịa ọrịa mkpụrụ ndụ ezubere iche adịlarị.

EGFR gosipụtara oke etuto dị iche iche siri ike, gụnyere NSCLC. EGFR gosipụtara nke ọma n'ọtụtụ (∼80%) carcinomas cell squamous cell, yana ihe dịka ọkara nke adenocarcinomas na nnukwu carcinomas. E gosipụtara ọrụ nke EGFR na mkpụrụ ndụ kansa kansa iji kwalite usoro metụtara mmụba mkpụrụ tumo, angiogenesis, mwakpo, na metastasis, yana igbochi apoptosis. EGFR (erbB1 ma ọ bụ HER1) bụ onye otu ezi na ụlọ erbB, nke gụnyekwara erbB2 (HER2), erbB3 (HER3), na erbB4 (HER4). Ọ bụ transmembrane glycoprotein nke mejupụtara extracellular ligand-binding domain, ngalaba transmembrane, na ngalaba intracellular na-ebugharị ngalaba na ọrụ tyrosine kinase. Mgbe o jikọtara ligand physiological dị ka ihe na-akpata epidermal, EGFR na-atụgharị ma ọ bụ monomer EGFR ọzọ ma ọ bụ onye ọzọ nke ezinụlọ erbB. Nke a na - eduga na ịmalite ọrụ nke tyrosine kinase, autophosphorylation nke tyrosine, na nnabata nke cascades nke na - emecha nweta nzaghachi dị iche iche dị ka ịba ụba sel. Ọzọkwa, okwu EGFR na etuto jikọtara na nzaghachi na-adịghị mma maka ọgwụgwọ, mmepe nke nguzogide ọgwụ cytotoxic, ọganihu ọrịa, na nlanarị dara ogbenye. Usoro ndị ọzọ nke ịbawanye EGFR nke nwere ike itinye aka na mmụba mkpụrụ ndụ gụnyere mmụba nke ligand extracellular, heterodimerization nke EGFR, na mgbanwe EGFR. Mostdị kachasị agbanwe agbanwe EGFR na etuto ahụ bụ EGFRvIII, nke a na-ahụ ihe ruru 39% nke okwu NSCLC. EGFRvIII na - ebu nhichapụ nhichapụ sitere na amino acid 6 ruo 273 na ngalaba njikọ nke extracellular ma gosipụta ọrụ tyrosine kinase nke na-anọghị na njikọta nke extracellular.

 

Reference

[1] Rukazenkov Y, Na-ekwu okwu G, Marshall G, et al. Epidermal na-ebute ihe na-anabata ihe tyrosine kinase inhibitors: yiri ma ọ dị iche? Anticancer Drugs 2009; 20: 856–866.

[2] Onye na-ebute ihe na-akpata epidermal na igbochi ya na ọgwụgwọ ọrịa kansa. Pharmacol Ther 1999; 82: 241-250.

[3] Ndị otu na-arụkọ ọrụ na Mkpụrụ Ọrịa Na-ahụ Maka Ọrịa. Chemotherapy na obere cancer cancer: a meta-analysis iji data emelitere na ndị ọrịa ọ bụla site na 52 nsogbu ụlọ ọgwụ. BMJ 1995; 311: 899–909.

[4] Douillard JY, Kim ES, Hirsh V, et al. Gefitinib (IRESSA) na docetaxel na ndị ọrịa nwere nnukwu ọrịa cancer ma ọ bụ metastatic nke na-abụghị obere cell cancer tupu a gwọọ ya na usoro ọgwụgwọ nke platinum: usoro ọmụmụ nke III, nke mepere emepe. J Thoracic Oncol 2007; Nkeji 2: PRS-02–

[5] Fukuoka M, Wu Y, Thongprasert S, et al. Ihe nyocha biomarker sitere na nke atọ III, nke a na-ahụkarị, nke a na-emeghe, nke mbụ, nke mbụ nke gefitinib (G) na carboplatin / paclitaxel (C / P) na ndị ọrịa ahọpụtara na-arịa ọrịa (pts) nwere ọrịa kansa na-abụghị obere cell (NSCLC) Asia (IPASS). J Ọrịa Oncol 2009; 27 Ntinye. 15: 8006–.

[6] Reck MA bu usoro buru ibu n'usoro ọgwụgwọ nke akwara akpa ume na gefitinib: ikpe IPASS na gafere. Ọkachamara Rev Anticancer Ther 2010; 10: 955-965.

[7] Barker, AJ Studies na-eduga na njirimara nke ZD1839 (IRESSA): onye na-arụsi ọrụ ike, na-ahọpụta onye na-anabata ihe na-akpata epidermal na-eme ka ọ ghara ịgwọ ọrịa kansa. Ihe omuma. Ahụike. Chem. Akwụkwọ. 11, 1911–1914 (2001).

[8] Wakeling, AE et al. ZD1839 (Iressa): onye na-arụ ọrụ nke na-arụ ọrụ nke epidermal na-egosi ihe nwere ike ịgwọ ọrịa kansa. Ọrịa Cancer. 62, 5749-5754 (2002).

[9] Yarden, Y. & Sliwkowski, MX Untpinye netwọk ErbB akara. Nature Rev. Mol. Cell Biol. 2, 127-137 (2001).

[10] Cersosimo, RJ Lung cancer: nyocha. Am. J. Ahụike Syst. Lọ ọgwụ. 59, 611-642 (2002).

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