卡利奇霉素

简介作用机制用途毒性生物活性靶点体外研究体内研究

卡利奇霉素

CAS号:108212-75-5
英文名:Calicheamicin
中文名:卡利奇霉素
CBNumber:CB01353750
分子式:C55H74IN3O21S4
分子量:1368.34
MOL File:108212-75-5.mol

卡利奇霉素化学性质

比旋光度 :D26 -124° (c = 0.98%, EtOH)
密度 :1.57±0.1 g/cm3(Predicted)
储存条件 :Store at -20°C
溶解度 :DMSO : ≥ 100 mg/mL (73.08 mM);Water : < 0.1 mg/mL (insoluble)
酸度系数(pKa) :7.13±0.60(Predicted)

卡利奇霉素性质、用途与生产工艺

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
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.