Dalotuzumab (MK-0646) 是一种靶向IGF-1R的重组人源化单克隆抗体 (IgG1 型)。Dalotuzumab 通过抑制IGF-1和IGF-2介导的肿瘤细胞增殖、IGF-1R自体磷酸化和Akt磷酸化而发挥作用。Dalotuzumab 还可诱导细胞凋亡和周期停滞。Dalotuzumab 与其他抗癌药物（如他汀类药物）共同使用，可增强 Dalotuzumab 的体外和体内抗肿瘤活性。
| 生物活性 | Dalotuzumab (MK-0646) is a recombinant humanized monoclonal antibody (IgG1 type) targetingIGF-1R. Dalotuzumab acts by inhibitingIGF-1- andIGF-2-mediated tumor cell proliferation,IGF-1Rautophosphorylation, andAktphosphorylation. Dalotuzumab also inducesapoptosisand cycle arrest. Dalotuzumab in combination with other anticancer drugs such as statins can enhance the antitumor activity of Dalotuzumab in vitro and in vivo[1][2][3]. |
体外研究
(In Vitro) | Dalotuzumab (h7C10; 33 nM; 24 h) 抑制 IGF-1 和 IGF-2 诱导的 MCF7 雌激素依赖性乳腺癌细胞增殖，IC50值分别为 4.2 和 3.1 nM[1]。
Dalotuzumab (33 nM; 24 h) 在 IGF-1 诱导的 MCF7 细胞中，诱导周期停滞，并抑制 IGF-IR 和 IRS-1 的自磷酸化[1]。
Dalotuzumab 使 NK 细胞介导的 MCF7 和 A459 细胞的裂解率分别提高了 26% 和 25%[1]。
Dalotuzumab (MK-0646; 10 μg/mL; 24, 48 h) 消除 IGF1 在子宫内膜癌细胞中的抗凋亡作用[2]。
Cell Proliferation Assay[1] | Cell Line: | MCF7 cells (IGF-1 and IGF-2-induced) | | Concentration: | 33 nM | | Incubation Time: | 24 h | | Result: | Showed anti-proliferation activity to IGF-1- and IGF-2-induced MCF7, with IC50values of 4.2 and 3.1 nM, respectively. |
Cell Cycle Analysis[1] | Cell Line: | MCF7 cells (IGF-1-induced) | | Concentration: | 33 nM | | Incubation Time: | 24 h | | Result: | Prevented cell cycle progression from the G1 to S and G2/M phases. |
Apoptosis Analysis[2] | Cell Line: | ECC-1 and USPC-1 cells (IGF-1-induced) | | Concentration: | 10 μg/mL | | Incubation Time: | 24, 48 h | | Result: | Reversed the effect of IGF1 on caspase-3 cleavage (Caspase-3 is activated in apoptotic cells and cleaves several cellular proteins, including PARP). |
Western Blot Analysis[1] | Cell Line: | MCF7 cells (IGF-1-induced) | | Concentration: | 33 nM | | Incubation Time: | 24 h | | Result: | Led to a decrease of phosphorylation for both β-chain and IRS-1. |
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体内研究
(In Vivo) | Dalotuzumab (h7C10; i.p.; 第一次 250 μg/小鼠，然后每周两次 125 μg/小鼠，持续 40 天) 显示对 MCF-7 和 A549 异种移植肿瘤模型的抗肿瘤作用[1]。
| Animal Model: | Swiss Nude mice (MCF-7 and A549 xenograft tumor models)[1]. | | Dosage: | 125 and 250 (first time) μg/mice | | Administration: | Intraperitoneal injection; 250 μg/mice for the first time, then 125 μg/mice twice weekly for 40 days | | Result: | Led to average tumor volume at 6 weeks post-cell injection was reduced by 70% and 72% in the MCF-7 and A549 models, respectively. |
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| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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