GEMTUZUMAB OZOGAMICIN

主成分: GEMTUZUMAB OZOGAMICIN (151 ~ 153 kDa)

商品名: MYLOTARG

中文名: 尚無中文譯名

美國食品藥物管理局首次核准時間與編號: 2017.09.01 [BLA #761060]

歐盟藥品管理局首次核准時間與編號: 2018.04.19 [EMEA/H/C/004204]

研發廠商: PFIZER—WYETH PHARMACEUTICALS藥廠(美國)/PFIZER藥廠(歐盟)

生物製劑序列: (EVQLVQSGAEVKKPGSSVKVSCKASGYTITDSNIHWVRQAPGQSLEWIGYIYPYNGGTDYNQKFKNRATLTVDNPTNTAYMELSSLRSEDTAFYYCVNGNPWLAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK)*2 + (DIQLTQSPSTLSASVGDRVTITCRASESLDNYGIRFLTWFQQKPGKAPKLLMYAASNQGSGVPSRFSGSGSGTEFTLTISSLQPDDFATYYCQQTKEVPWSFGQGTKVEVKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC)*2 + (N-Acetyl-gamma-calicheamicin dimethylhydrazide with a acid-cleavable linker: 4-(4-acetylphenoxy) butanoic acid)*(0~6)

IUPAC名: N-Acetyl-gamma-calicheamicin dimethylhydrazide: S-[(2R,3S,4S,6S)-6-[[(2R,3S,4S,5R,6R)-5-[(2S,4S,5S)-5-[acetyl(ethyl)amino]-4-methoxyoxan-2-yl]oxy-6-[[(2S,5Z,9R,13E)-13-[2-[(4-hydrazinyl-2-methyl-4-oxobutan-2-yl)disulfanyl]ethylidene]-9-hydroxy-12-(methoxycarbonylamino)-11-oxo-2-bicyclo[7.3.1]trideca-1(12),5-dien-3,7-diynyl]oxy]-4-hydroxy-2-methyloxan-3-yl]amino]oxy-4-hydroxy-2-methyloxan-3-yl] 4-[(2S,3R,4R,5S,6S)-3,5-dihydroxy-4-methoxy-6-methyloxan-2-yl]oxy-5-iodo-2,3-dimethoxy-6-methylbenzenecarbothioate 

分子線性簡式(SMILES): N-Acetyl-gamma-calicheamicin dimethylhydrazide: CCN(C1COC(CC1OC)OC2C(C(C(OC2OC3C#CC=CC#CC4(CC(=O)C(=C3C4=CCSSC(C)(C)CC(=O)NN)NC(=O)OC)O)C)NOC5CC(C(C(O5)C)SC(=O)C6=C(C(=C(C(=C6OC)OC)OC7C(C(C(C(O7)C)O)OC)O)I)C)O)O)C(=O)C

公共化合物資料庫(PubChem): 

• Gemtuzumab Ozogamicin: 不適用/CAS編號: 220578-59-6

• N-Acetyl-gamma-calicheamicin dimethylhydrazide: 86567977/CAS編號: 136185-00-7

• Ozogamicin: 9942071/CAS編號: 400046-53-9

英文仿單: U.S. FDA英文仿單 SUPPL-4；EMA英文仿單 R/0025

給藥途徑: 靜脈輸注(intravenous infusion)

劑量: 4.5 mg凍乾粉 [先與符合美國藥典標準的5毫升室溫無菌注射用水重構，再取4.5毫升重構液與符合美國藥典標準的0.9%氯化鈉注射液稀釋成最終濃度為0.075~0.234 mg/mL後使用(reconstitute each vial with 5 mL of sterile water for injection, USP, to obtain a concentration of 1 mg/mL of MYLOTARG that delivers 4.5 mL. Add the reconstituted MYLOTARG solution to a syringe with 0.9% Sodium Chloride Injection to a final concentration between 0.075 mg/mL to 0.234 mg/mL.)]

機制: GEMTUZUMAB OZOGAMICIN為抗CD33抗體GEMTUZUMAB與棘孢小單孢菌(Micromonospora echinospora)產生的calicheamicin類抗生素OZOGAMICIN組成的抗體-藥物複合體(antibody-drug conjugate)，帶有CD33分化群抗原的白血病母細胞(leukemic blasts)與骨髓單核細胞譜系之未成熟正常細胞(immature normal cells of myelomonocytic lineage)，會因為GEMTUZUMAB的結合而將GEMTUZUMAB OZOGAMICIN攝入，並使OZOGAMICIN在細胞內釋出，造成雙股DNA斷裂，而誘發細胞週期停滯與細胞凋亡(cell cycle arrest and apoptotic cell death)。

適應症:

1. 血液淋巴惡性腫瘤|急性骨髓性白血病(AML, acute myeloid leukemia):

用於治療CD33陽性急性骨髓性白血病(AML, acute myeloid leukemia)，且須符合下述任一條件:

1. • 1個月大以上兒童與成人的新診斷急性骨髓性白血病(AML, acute myeloid leukemia)；

   • 2歲以上兒童與成人的復發或難治性急性骨髓性白血病(AML, acute myeloid leukemia)；

潛在靶點與作用機轉: 

• • 己醣基轉移酶(hexosyltransferase)

    1. CALG1卡奇黴素鼠李醣轉移酶(calicheamicin 3'-O-methyl-rhamnosyltransferase CalG1)

       • 棘孢小單孢菌CALG1與OZOGAMICIN類似物的視覺化立體交互作用: 3OTH_CLJ (RCSB)

中華民國藥品許可與健保價格(中文的用法、劑量、副作用等資訊詳見各連結內之仿單資料連結): 食品藥物管理署尚未核准GEMTUZUMAB OZOGAMICIN