SQ609
目录号 : GC62441
SQ609 是一种来自二哌啶库的先导化合物。SQ609 在 4μg/ml时抑制 90% 以上的细胞内细菌生长，并且对这些细胞有毒。SQ609 显示出强大的抗结核活性。
Cas No.:627052-25-9
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
SQ609 is a lead compound from a library of dipiperidines. SQ609 inhibits more than 90% of intracellular bacterial growth at 4μg/ml and is toxic to these cells. SQ609 displays a potent antitubercular activity [1].
In Mtb-infected macrophages in vitro, SQ609 inhibits more than 90% of intracellular bacterial growth at 4μg/ml and is toxic to these cells[1].
SQ609 (10 mg/kg; intravenous injection) completely prevents weight loss in the Mtb-infected animals and prolongs the therapeutic effect following drug withdrawal for another 10-15 days[1].
[1]. Bogatcheva E, et al. Identification of SQ609 as a lead compound from a library of dipiperidines. Bioorg Med Chem Lett. 2011;21(18):5353-5357.
| Cas No. | 627052-25-9 | SDF | |
| 分子式 | C22H38N2O | 分子量 | 346.55 |
| 溶解度 | DMSO : 6.67 mg/mL (19.25 mM; ultrasonic and warming and heat to 60°C) | 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 | 2.8856 mL | 14.4279 mL | 28.8559 mL |
| 5 mM | 0.5771 mL | 2.8856 mL | 5.7712 mL |
| 10 mM | 0.2886 mL | 1.4428 mL | 2.8856 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。
Identification of SQ609 as a lead compound from a library of dipiperidines
Bioorg Med Chem Lett 2011 Sep 15;21(18):5353-7.PMID:21807506DOI:10.1016/j.bmcl.2011.07.015.
We recently reported that compounds created around a dipiperidine scaffold demonstrated activity against Mycobacterium tuberculosis (Mtb) (Bogatcheva, E.; Hanrahan, C.; Chen, P.; Gearhart, J.; Sacksteder, K.; Einck, L.; Nacy, C.; Protopopova, M. Bioorg. Med. Chem. Lett.2010, 20, 201). To optimize the dipiperidine compound series and to select a lead compound to advance into preclinical studies, we evaluated the structure-activity relationship (SAR) of our proprietary libraries. The (piperidin-4-ylmethyl)piperidine scaffold was an essential structural element required for antibacterial activity. Based on SAR, we synthesized a focused library of 313 new dipiperidines to delineate additional structural features responsible for antitubercular activity. Thirty new active compounds with MIC 10-20 μg/ml on Mtb were identified, but none was better than the original hits of this series, SQ609, SQ614, and SQ615. In Mtb-infected macrophages in vitro, SQ609 and SQ614 inhibited more than 90% of intracellular bacterial growth at 4 μg/ml; SQ615 was toxic to these cells. In mice infected with Mtb, weight loss was completely prevented by SQ609, but not SQ614, and SQ609 had a prolonged therapeutic effect, extended by 10-15 days, after cessation of therapy. Based on in vitro and in vivo antitubercular activity, SQ609 was identified as the best-in-class dipiperidine compound in the series.
ADVANCES IN PHARMACOTHERAPY OF TUBERCULOSIS
Acta Pol Pharm 2017 Jan;74(1):3-11.PMID:29474756doi
Tuberculosis remains a growing threat of infectious diseases of twenty-first century. An attempt to find new antituberculosis agents was made especially to treat multidrug-resistant and extensively drug-resistant tuberculosis. One of the most promising drugs is bedaquiline - a new drug approved by Food and Drug Administration (FDA) and by the European Union countries. This compound is intended to treat multidrug-resistant pulmonary tuberculosis in adult patients in combination regimens in case of impossibility of using other drugs. This paper is also focused on some interesting molecules in treating multidrug-resistant tuberculosis which are currently tested in clinical studies: delamanid (dihydro-nitroimidazooxazole derivative, phase III), AZD5847 (oxazolidinone derivative, phase II), pretomanid (nitroimidazole derivative, phase III), sutezolid (oxazolidinone derivative, phase II) and SQ109 (ethambutol analogue, phase II) and some prospective molecules at the level of preclinical studies e.g., CPZEN-45, SQ609 and SQ641.
The anti-tuberculosis agents under development and the challenges ahead
Future Med Chem 2015;7(15):1981-2003.PMID:26505682DOI:10.4155/fmc.15.128.
Tuberculosis (TB) is a serious health problem causing 1.5 million deaths worldwide. After the discovery of first-line anti-TB drugs, the mortality rate declined sharply, however, the emergence of drug-resistant strains and HIV co-infection have led to increased incidence of this disease. A number of new potential antitubercular drug candidates with novel modes of action have entered clinical trials in recent years. Compounds such as gatifloxacin, moxifloxacin and linezolid, the already known antibiotics are currently being evaluated for their anti-TB activity. OPC-67683 and TMC207 have been approved for the treatment of MDR-TB patients recently, while PA-824, SQ109, PNU-100480, AZD5847, LL3858, SQ609, SQ641, BTZ043, DC-159a, CPZEN-45, Q-203, DNB1, TBA-354 are in various phases of clinical and preclinical developments. This review evaluates the current status of TB drug development and future aspects.
Tuberculosis: the drug development pipeline at a glance
Eur J Med Chem 2012 May;51:1-16.PMID:22421275DOI:10.1016/j.ejmech.2012.02.033.
Tuberculosis is a major disease causing every year 1.8 million deaths worldwide and represents the leading cause of mortality resulting from a bacterial infection. Introduction in the 60's of first-line drug regimen resulted in the control of the disease and TB was perceived as defeating. However, since the progression of HIV leading to co-infection with AIDS and the emergence of drug resistant strains, the need of new anti-tuberculosis drugs was not overstated. However in the past 40 years any new molecule did succeed in reaching the market. Today, the pipeline of potential new treatments has been fulfilled with several compounds in clinical trials or preclinical development with promising activities against sensitive and resistant Mycobacterium tuberculosis strains. Compounds as gatifloxacin, moxifloxacin, metronidazole or linezolid already used against other bacterial infections are currently evaluated in clinical phases 2 or 3 for treating tuberculosis. In addition, analogues of known TB drugs (PA-824, OPC-67683, PNU-100480, AZD5847, SQ609, SQ109, DC-159a) and new chemical entities (TMC207, BTZ043, DNB1, BDM31343) are under development. In this review, we report the chemical synthesis, mode of action when known, in vitro and in vivo activities and clinical data of all current small molecules targeting tuberculosis.