Anticancer agent 81 (Compound 37b3) 是一种抗癌剂，能诱导肿瘤细胞周期阻滞和凋亡 (
apoptosis)。Anticancer agent 81 可作为有效载荷与 Trastuzumab (HY-P9907) 结合得到抗体偶联药物 (
ADC) T-PBA。T-PBA 维持了 Trastuzumab 的靶向模式和内化能力。
| 生物活性 |
Anticancer agent 81 (Compound 37b3) is an anticancer agent and can induce tumor cell cycle arrest andapoptosis. Anticancer agent 81 can be used as a payload to conjugate withTrastuzumab(HY-P9907) to obtain theantibody–drug conjugate(ADC) T-PBA. T-PBA maintained its mode of target and internalization ability of Trastuzumab[1].
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体外研究
(In Vitro) |
Anticancer agent 81 (Compound 37b3) (72 h) shows cytotoxicity against SKOV3, MDA-MB-231 and NCI-N87 cells[1].
Anticancer agent 81 (0-5 μM) induces DNA interstrand cross-linking[1].
Anticancer agent 81 (0-3 nM; 24 h) arrests SKOV3 cell cycle at the S-phase[1].
Anticancer agent 81 (0-3 nM; 48 h) induces SKOV3 cell apoptosis[1].
Anticancer agent 81 (25 nM; 12 h) acts on DNA in the nucleus after entering SKOV3 cells and MDA-MB-231 cells[1].
Anticancer agent 81 induces DDR signaling pathways via cross-linking DNA and then activates the caspase cascade and PARP, finally leading to cell cycle arrest and apoptosis[1].
Anticancer agent 81 covalently binds to the DNA sequences and acts on the major groove of DNA[1].
Cell Cytotoxicity Assay[1]
| Cell Line: |
SKOV3, MDA-MB-231 and NCI-N87 |
| Concentration: |
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| Incubation Time: |
72 h |
| Result: |
Showed cytotoxicity with IC50s of 0.17 ± 0.07, 0.90 ± 0.11 and 0.94 ± 0.14 nM against SKOV3, MDA-MB-231 and NCI-N87 cells, respectively. |
Cell Cycle Analysis[1]
| Cell Line: |
SKOV3 |
| Concentration: |
0.33, 1 and 3 nM |
| Incubation Time: |
24 h |
| Result: |
Inhibited the cell cycle at the S-phase. |
Apoptosis Analysis[1]
| Cell Line: |
SKOV3 |
| Concentration: |
0.33, 1 and 3 nM |
| Incubation Time: |
48 h |
| Result: |
Induced cell apoptosis in a concentration-dependent manner. |
Western Blot Analysis[1]
| Cell Line: |
SKOV3 and NCI-N87 |
| Concentration: |
0.02, 0.1, 0.5, 2.5 and 12.5 nM |
| Incubation Time: |
48 h |
| Result: |
Induced the phosphorylation of histone 2AX (γ-H2AX) in a dose-dependent manner. Induced the cleavage of PARP (cPARP) and caspase 3 (cCas3) in a concentration-dependent manner. |
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体内研究
(In Vivo) |
T-PBA (1-10 mg/kg; i.v.; every 3 days for 4 times) could significantly delay tumor growth in two Her2-positive xenograft models in mice without obvious toxicity and side effects, and the effect is better than Trastuzumab[1].
| Animal Model: |
Female balb/c nude mice, SKOV3 and NCI-N87 tumor model[1] |
| Dosage: |
1, 5 and 10 mg/kg |
| Administration: |
Tail vein injection on days 0, 3, 6, and 9 |
| Result: |
Inhibited tumor growth in a dose-dependent manner (57.5% inhibition at 1 mg/kg, 70.0% inhibition at 5 mg/kg, and 91.5% inhibition at 10 mg/kg in SKOV3 tumor model; the tumor growth inhibitory rate was 50.2% for 1 mg/kg, 88.0% for 5 mg/kg, and 97.1% for 10 mg/kg in NCI-N87 tumor model) without obvious side effects. |
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| 分子量 |
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| Formula |
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| 运输条件 |
Room temperature in continental US; may vary elsewhere.
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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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