SGD-1882
(Synonyms: PBD dimer) 目录号 : GC63189
SGD-1882 是一种有细胞毒性的 DNA 小沟交联剂，为 PBD 二聚体，可以作为 ADC 的有效载荷。
Cas No.:1222490-34-7
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
SGD-1882 is a cytotoxic, DNA minor-groove crosslinking agent pyrrolobenzodiazepine (PBD) dimer, acting as the payload for ADCs.
SGD-1882 is the cytotoxic payload undergoing clinical evaluation for anti-CD33 and anti-CD70 conjugates[1]. SGD-1882 is not an MDR1 substrate, and SGN-CD33A is conjugated to the SGD-1882. SGN-CD33A can kill MDR1 expressing CD33 positive AML patient samples and is currently in Phase I[2].
[1]. Eunhee G. Kim, et al. Strategies and Advancement in Antibody-Drug Conjugate Optimization for Targeted Cancer Therapeutics. Biomol Ther (Seoul). 2015 Nov; 23(6): 493-509.
[2]. Dowdy Jackson, et al. Using the Lessons Learned From the Clinic to Improve the Preclinical Development of Antibody Drug Conjugates. Pharm Res. 2015; 32(11): 3458-3469.
| Cas No. | 1222490-34-7 | SDF | |
| 别名 | PBD dimer | ||
| 分子式 | C42H39N5O7 | 分子量 | 725.79 |
| 溶解度 | 储存条件 | Store at -20°C | |
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.3778 mL | 6.889 mL | 13.7781 mL |
| 5 mM | 0.2756 mL | 1.3778 mL | 2.7556 mL |
| 10 mM | 0.1378 mL | 0.6889 mL | 1.3778 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。
A first-in-human, phase 1, dose-escalation study of ABBV-176, an antibody-drug conjugate targeting the prolactin receptor, in patients with advanced solid tumors
Invest New Drugs 2020 Dec;38(6):1815-1825.PMID:32524319DOI:10.1007/s10637-020-00960-z
ABBV-176 is an antibody-drug conjugate composed of the humanized antibody h16f (PR-1594804) conjugated to a highly potent, cytotoxic cross-linking pyrrolobenzodiazepine dimer (PBD; SGD-1882) targeting the prolactin receptor (PRLR), which is overexpressed in several solid tumor types. This phase 1, dose-escalation study (NCT03145909) evaluated the safety, pharmacokinetics, and preliminary activity of ABBV-176 in patients with advanced solid tumors likely to exhibit elevated levels of PRLR. Patients received ABBV-176 once every 3 weeks. Dose escalation was by an exposure-adjusted, continual reassessment method. Dose-limiting toxicities (DLTs) were assessed from the first day of dosing until the next dose of ABBV-176 to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Nineteen patients received ABBV-176 at doses from 2.7-109.35 μg/kg. Patients enrolled had colorectal cancer (n = 11), breast cancer (n = 6), or adrenocortical carcinoma (n = 2). DLTs occurred in 4 patients and included thrombocytopenia (n = 2; both at 99.9-μg/kg dose level), neutropenia (n = 2; 78.3-μg/kg and 99.9-μg/kg dose levels), and pancytopenia (n = 1; 109.35-μg/kg dose level). The most common treatment-emergent adverse events related to ABBV-176 were thrombocytopenia, neutropenia, increased aspartate aminotransferase, nausea, fatigue, and pleural effusions. Effusions and edema were common, and timing of onset suggested possible cumulative ABBV-176 toxicity. Tumor expression of PRLR varied among patients enrolled and analyzed. No patient had an objective response. MTD was not formally determined, as identification of a tolerable dose was confounded by late-onset toxicities. ABBV-176 was associated with significant toxicity in this phase 1, dose-escalation study. Although cytopenias were often dose limiting, effusions and edema were also common and had late onset that suggested cumulative toxicity. No responses were observed, although data were available from a small number of patients with variable tumor PRLR expression. This study was terminated after the dosing of 19 patients.