CL2A-SN-38
目录号 : GC60714
An antibody-drug conjugate containing SN-38
Cas No.:1279680-68-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
CL2A-SN-38 is a cleavable linker-based antibody-drug conjugate (ADC) containing the topoisomerase I inhibitor SN-38 and a maleimidocaproyl linker.1 CL2A-SN-38 has been linked to tumor-selective humanized antibodies, such as anti-Trop-2 (hRS7), to target SN-38 to tumor sites. CL2A-SN-38 linked to hRS7 is cytotoxic to Calu-3, COLO 205, Capan-1, PC3, SK-MES-1, and BxPC-3 cancer cells (IC50s =1.95-23.14 nM). CL2A-SN-38 linked to hRS7 reduces tumor growth in BxPC-3 pancreatic and SK-MES-1 lung cancer mouse xenograft models.
1.Cardillo, T.M., Govindan, S.V., Sharkey, R.M., et al.Humanized anti-Trop-2 IgG-SN-38 conjugate for effective treatment of diverse epithelial cancers: Preclinical studies in human cancer xenograft models and monkeysClin. Cancer Res.17(10)3157-3169(2011)
| Cas No. | 1279680-68-0 | SDF | |
| Canonical SMILES | O=C(O[C@](C1=C(CO2)C(N3CC4=C(CC)C5=CC(O)=CC=C5N=C4C3=C1)=O)(CC)C2=O)OCC6=CC=C(NC([C@H](CCCCN)NC(COCC(NCCOCCOCCOCCOCCOCCOCCOCCOCCN7N=NC(CNC(C8CCC(CN9C(C=CC9=O)=O)CC8)=O)=C7)=O)=O)=O)C=C6 | ||
| 分子式 | C73H97N11O22 | 分子量 | 1480.61 |
| 溶解度 | DMSO: 100 mg/mL (67.54 mM) | 储存条件 | -20°C, stored under nitrogen, away from moisture |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 0.6754 mL | 3.377 mL | 6.754 mL |
| 5 mM | 0.1351 mL | 0.6754 mL | 1.3508 mL |
| 10 mM | 0.0675 mL | 0.3377 mL | 0.6754 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Humanized anti-Trop-2 IgG-SN-38 conjugate for effective treatment of diverse epithelial cancers: preclinical studies in human cancer xenograft models and monkeys
Clin Cancer Res 2011 May 15;17(10):3157-69.PMID:21372224DOI:10.1158/1078-0432.CCR-10-2939.
Purpose: Evaluate the efficacy of an SN-38-anti-Trop-2 antibody-drug conjugate (ADC) against several human solid tumor types, and to assess its tolerability in mice and monkeys, the latter with tissue cross-reactivity to hRS7 similar to humans. Experimental design: Two SN-38 derivatives, CL2-SN-38 and CL2A-SN-38, were conjugated to the anti-Trop-2-humanized antibody, hRS7. The immunoconjugates were characterized in vitro for stability, binding, and cytotoxicity. Efficacy was tested in five different human solid tumor-xenograft models that expressed Trop-2 antigen. Toxicity was assessed in mice and in Cynomolgus monkeys. Results: The hRS7 conjugates of the two SN-38 derivatives were equivalent in drug substitution (∼ 6), cell binding (K(d) ∼ 1.2 nmol/L), cytotoxicity (IC(50) ∼ 2.2 nmol/L), and serum stability in vitro (t/(½) ∼ 20 hours). Exposure of cells to the ADC demonstrated signaling pathways leading to PARP cleavage, but differences versus free SN-38 in p53 and p21 upregulation were noted. Significant antitumor effects were produced by hRS7-SN-38 at nontoxic doses in mice bearing Calu-3 (P ≤ 0.05), Capan-1 (P < 0.018), BxPC-3 (P < 0.005), and COLO 205 tumors (P < 0.033) when compared to nontargeting control ADCs. Mice tolerated a dose of 2 × 12 mg/kg (SN-38 equivalents) with only short-lived elevations in ALT and AST liver enzyme levels. Cynomolgus monkeys infused with 2 × 0.96 mg/kg exhibited only transient decreases in blood counts, although, importantly, the values did not fall below normal ranges. Conclusions: The anti-Trop-2 hRS7-CL2A-SN-38 ADC provides significant and specific antitumor effects against a range of human solid tumor types. It is well tolerated in monkeys, with tissue Trop-2 expression similar to humans, at clinically relevant doses, and warrants clinical investigation.