卡利奇霉素

中文名称:

卡利奇霉素

中文同义词:

卡奇霉素 GAMMA1;卡利奇霉素;刺孢霉素;加利西霉素Γ1;CALICHEAMICIN卡利奇霉素;卡奇霉素Γ1;卡奇霉素;卡里奇霉素

英文名称:

calicheamicin gamma(1)I

英文同义词:

calicheamicin gamma(1)I;Benzenecarbothioic acid, 4-((6-deoxy-3-o-methyl-alpha-L-mannopyranosyl)oxy)-3-iodo-5,6-dimethoxy-2-methyl-, 4-ester with methyl (8-((4,6-dideoxy-2-o-(2,4-dideoxy-4-(ethylamino)-3-o-methyl-alpha-L-threo-pentapyranosyl)-4-(((2,6-dideoxy-4-thio-beta-D-ribo-hexopyranosyl)oxy)amino)-beta-D-glucopyranosyl)oxy)-1-hydroxy-13-(2-(methyltrithio)ethylidene)-11-oxobicyclo(7.3.1)trideca-4,9-diene-2,6-diyn-10-yl)carbamate, (1R-(1R*,4Z,8S*,13E))-;Calichemicin gamma1;Carbamic acid, ((1R,4Z,8S,13E)-8-((4,6-dideoxy-4-(((2,6-dideoxy-4-S-(4-((6-deoxy-3-o-methyl-alpha-L-mannopyranopyranosyl)oxy)-3-iodo-5,6-dimethoxy-2-methylbenzoyl)-4-thio-beta-D-ribo-hexopyranosyl)oxy)amino)-2-o-(2,4-dideoxy-4-(ethylamino)-3-o-methyl-alpha-L-threo-pentopyranosyl)-beta-D-glucopyranosyl)oxy)-1-hydroxy-13-(2-(methyltrithio)ethylidene)-11-oxobicyclo(7.3.1)trideca-4,9-diene-2,6-diyn-10-yl)-, methyl ester;Calicheamicin γ1;LL-E 33288 gamma1-I;calicheamicin gamma;Calicheamicin γ1 purity>95

CAS号:

108212-75-5

分子式:

C55H74IN3O21S4

分子量:

1368.35

EINECS号:

相关类别:

原料药【仅供科研】;医药原料药;科研原药系列;原料药;ADC;Pharmaceutical

Mol文件:

Mol File

比旋光度 

D26 -124° (c = 0.98%, EtOH)

密度 

1.57±0.1 g/cm3(Predicted)

酸度系数(pKa)

7.13±0.60(Predicted)

CAS 数据库

108212-75-5

简介

卡奇霉素（calicheamicins，CLM）是从稀有放线茵小单孢菌发酵液中分离得到的烯二炔类抗肿瘤抗生素。

作用机制

卡奇霉素的生物活性浓度＜1 Pg·mL-1，对白血病如淋巴细胞白血病P388和L1210细胞以及实体瘤如结肠癌26和黑色素瘤B-16细胞有极强的杀伤作用。卡奇霉素生物活性的发挥主要通过与细胞DNA特异序列的小沟结合，直接断裂细胞DNA，进一步诱导肿瘤细胞凋亡，同时，卡奇霉素对细胞RNA也有非特异性的损伤作用，卡奇霉素与抗CD33单抗偶联物Mylotarg是第一个被FDA批准用于肿瘤治疗的单抗导向药物，已在临床应用。

用途

卡奇霉素是一种有效的细胞毒性试剂,可引起DNA双链断裂。

毒性

卡奇霉素有剧毒，是土壤细菌产生的数百种代谢物之一。

生物活性

Calicheamicin 是一种肿瘤抗生素，也是有效的细胞毒性试剂，可引起DNA双链断裂。Calicheamicin 抑制 DNA 合成。

靶点

Calicheamicins

Calicheamicins

体外研究

PF-06647263 (anti-EFNA4-ADC) is generated via conjugation of hE22 lysine residues to the AcButDMH-N-Ac-calicheamicin-γ1 linker-payload with an average drug-to-antibody ratio (DAR) of 4.6. PF-06647263 elicits antigen- and concentration-dependent cytotoxicity, as exposure to PF-06647263 for 96 hours results in cell death (EC 50 = appr 1 ng/mL). CMC-544, consisting of a humanized CD22 Ab linked to calicheamicin, is effective in pediatric primary B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells in vitro. CMC-544 induces cell death in various ALL cell lines in a dose- and time-dependent way, with IC 50 values ranging from 0.15 to 4.9 ng/mL. CMC-544 (10 ng/mL) is effective and specific in primary BCP-ALL cells. In CMC-544-treated cells, the level of CD22 has decreased relative to that on G5/44-treated cells and continued to decrease.

体内研究

An ADC comprising a humanized anti-EFNA4 monoclonal antibody conjugated to the DNA-damaging agent calicheamicin achieves sustained tumor regressions in both TNBC and ovarian cancer PDX in vivo. PF-06647263 (0.27, 0.36 mg/kg) results in significant tumor regressions in TNBC xenografts.