TTT-28
目录号 : GC37832
TTT-28 是一种噻唑-缬氨酸肽模拟物，高效 ABCB1 (P-gp/MDR1) 选择性抑制剂，低毒性。TTT-28 通过选择性阻断 ATP 结合盒亚家族 B 成员1 (ABCB1) 的外排功能, 逆转ABCB1介导的多药耐药性 (MDR)。
Cas No.:1609138-51-3
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
TTT-28 is a synthesized thiazole-valine peptidomimetic, a novel selective inhibitor of ABCB1 (P-gp/MDR1) with high efficacy and low toxicity, which reverses the ATP-binding cassette sub-family B member 1 (ABCB1)-mediated Multidrug resistance (MDR) by selectively blocking the efflux function of ABCB1[1].
TTT-28 (0-100 μM; 72 hours) reverses ABCB1-mediated MDR in drug selected SW620/Ad300 cells and transfected HEK293/ABCB1 cells; the IC50s of TTT-28 in CCD-18Co, SW620 and SW620/Ad300 cells are 213.4±11.0 μM, 89.4±3.9 μM and 92.0±5.0 μM, respectively[1].TTT-28 (10 μM; 2 hours) raises the ABCB1-mediated MDR and increased the accumulation of [3H]-paclitaxel in ABCB1 overexpressing cells[1].TTT-28 (10 μM; 0-72 hours) does not interfer with the expression level and localization of ABCB1, it results from blocking the efflux function of ABCB1[1].TTT-28 (0-40 μM; 2 hours) interacts at the drug-substrate-binding site and actives the ATPase activity of ABCB1 in a concentration-dependent fashion[1]. Cell Viability Assay[1] Cell Line: SW620 cells, SW620/Ad300 cells
TTT-28 (deliver orally; 30 mg/kg; every 3 rd day; 18 days) potentiates the anticancer activity of paclitaxel due to its inhibitory effect on the efflux function of ABCB1, it enhances the inhibitory effect of paclitaxel on the growth of SW620/Ad300 tumor and promoted apoptosis[1]. Animal Model: 5-10 week Male athymic NCR (nu/nu) nude mice ABCB1 overexpressing tumor xenograft model with SW620/Ad300 cells
[1]. Wang YJ, et al. Thiazole-valine peptidomimetic (TTT-28) antagonizes multidrug resistance in vitro and in vivo by selectively inhibiting the efflux activity of ABCB1. Sci Rep. 2017 Feb 9;7:42106.
| Cas No. | 1609138-51-3 | SDF | |
| Canonical SMILES | O=C(N[C@@H](C(C)C)C1=NC(C(NC2=CC=CC=C2C(C3=CC=CC=C3)=O)=O)=CS1)C4=CC(OC)=C(OC)C(OC)=C4 | ||
| 分子式 | C31H31N3O6S | 分子量 | 573.66 |
| 溶解度 | Soluble in DMSO | 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7432 mL | 8.716 mL | 17.4319 mL |
| 5 mM | 0.3486 mL | 1.7432 mL | 3.4864 mL |
| 10 mM | 0.1743 mL | 0.8716 mL | 1.7432 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。
Thiazole-valine peptidomimetic (TTT-28) antagonizes multidrug resistance in vitro and in vivo by selectively inhibiting the efflux activity of ABCB1
Sci Rep 2017 Feb 9;7:42106.PMID:28181548DOI:PMC5299601
Multidrug resistance (MDR) attenuates the chemotherapy efficacy and increases the probability of cancer recurrence. The accelerated drug efflux mediated by ATP-binding cassette (ABC) transporters is one of the major MDR mechanisms. This study investigated if TTT-28, a newly synthesized thiazole-valine peptidomimetic, could reverse ABCB1-mediated MDR in vitro and in vivo. TTT-28 reversed the ABCB1-mediated MDR and increased the accumulation of [3H]-paclitaxel in ABCB1 overexpressing cells by selectively blocking the efflux function of ABCB1, but not interfering with the expression level and localization of ABCB1. Animal study revealed that TTT-28 enhanced the intratumoral concentration of paclitaxel and promoted apoptosis, thereby potently inhibiting the growth of ABCB1 overexpressing tumors. But TTT-28 did not induce the toxicity (cardiotoxicity/myelosuppression) of paclitaxel in mice. In this study, we synthesized and evaluated a novel selective inhibitor of ABCB1 (TTT-28) with high efficacy and low toxicity. The identification and characterization of this new thiazole-valine peptidomimetic will facilitate design and synthesis of a new generation of ABCB1 inhibitors, leading to further research on multidrug resistance and combination chemotherapy. Furthermore, the strategy that co-administer MDR-ABCB1 inhibitor to overcome the resistance of one FDA approved, widely used chemotherapeutic paclitaxel, may be promising direction for the field of adjuvant chemotherapy.