SQ109
(Synonyms: NSC 722041;SQ-109;SQ 109) 目录号 : GC12722
SQ109是一种新型的氨苄青霉素结核杆菌细胞壁合成抑制剂，能够通过干扰分枝杆菌酸和细胞壁其他组分的生物合成，有效抑制结核分枝杆菌（Mtb）的生长。
Cas No.:502487-67-4
Sample solution is provided at 25 µL, 10mM.
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SQ109 is a novel, ampicillin-type, Mycobacterium tuberculosis cell wall synthesis inhibitor that effectively inhibits the growth of Mycobacterium tuberculosis (Mtb) by interfering with the biosynthesis of mycolic acid and other cell wall components[1, 2]. SQ109 is a synthetic, small-molecule, diamine-type anti-tuberculosis drug that targets and inhibits Mycobacterium membrane protein L3 (MmpL3), making it useful for treating drug-resistant tuberculosis[3]. SQ109 effectively inhibits the growth of the parasitic protozoan Trypanosoma brucei, killing the cells with an IC50 value of 50±8nM[4].
In vitro, treatment of Leishmania donovani-infected macrophages with SQ109 (0-10μM) for 48h inhibited the proliferation of L. donovani parasites in a dose-dependent manner[5]. Treatment of M. tuberculosis with SQ109 (10, 20μM) for 5 and 10 days, respectively, reduced the bacterial colony count by 1 and 2 log10 units[6].
In vivo, intraperitoneal injection of SQ109 (30, 100mg/kg/day) for 5 days in mice infected with Leishmania parasites significantly reduced the parasite burden in the blood and prolonged mouse survival; however, the parasite burden in the blood increased rapidly after treatment cessation[7].
References:
[1] Tahlan K, Wilson R, Kastrinsky D B, et al. SQ109 targets MmpL3, a membrane transporter of trehalose monomycolate involved in mycolic acid donation to the cell wall core of Mycobacterium tuberculosis[J]. Antimicrobial agents and chemotherapy, 2012, 56(4): 1797-1809.
[2] Sacksteder K A, Protopopova M, Barry C E, et al. Discovery and development of SQ109: a new antitubercular drug with a novel mechanism of action[J]. Future microbiology, 2012, 7(7): 823-837.
[3] Li K, Schurig-Briccio L A, Feng X, et al. Multitarget drug discovery for tuberculosis and other infectious diseases[J]. Journal of medicinal chemistry, 2014, 57(7): 3126-3139.
[4] Veiga-Santos P, Li K, Lameira L, et al. SQ109, a new drug lead for Chagas disease[J]. Antimicrobial agents and chemotherapy, 2015, 59(4): 1950-1961.
[5] Gil Z, Martinez-Sotillo N, Pinto-Martinez A, et al. SQ109 inhibits proliferation of Leishmania donovani by disruption of intracellular Ca2+ homeostasis, collapsing the mitochondrial electrochemical potential (Δ Ψ m) and affecting acidocalcisomes[J]. Parasitology research, 2020, 119(2): 649-657.
[6] Zheng H, Williams J T, Coulson G B, et al. HC2091 kills Mycobacterium tuberculosis by targeting the MmpL3 mycolic acid transporter[J]. Antimicrobial agents and chemotherapy, 2018, 62(7): 10.1128/aac. 02459-17.
[7] Baek K H, Phan T N, Malwal S R, et al. In vivo efficacy of SQ109 against Leishmania donovani, Trypanosoma spp. and Toxoplasma gondii and in vitro activity of SQ109 metabolites[J]. Biomedicines, 2022, 10(3): 670.
SQ109是一种新型的氨苄青霉素结核杆菌细胞壁合成抑制剂，能够通过干扰分枝杆菌酸和细胞壁其他组分的生物合成，有效抑制结核分枝杆菌（Mtb）的生长[1, 2]。SQ109是一种合成的小分子二胺类抗结核药物，能够靶向抑制分枝杆菌膜蛋白大3（MmpL3），用于治疗耐药结核病[3]。SQ109能够有效抑制寄生虫的锥虫成虫期，杀死细胞，IC50值为50±8nM[4]。
在体外，SQ109（0-10μM）处理感染了利什曼原虫（L. donovani）寄生虫的巨噬细胞48h，以剂量依赖性方式抑制了L. donovani幼虫的增殖[5]。SQ109（10, 20μM）处理结核分枝杆菌5天和10天，分别使菌落数降低了1个和2个对数[6]。
在体内，SQ109（30, 100mg/kg/day）通过腹腔注射治疗寄生虫血症小鼠5天，显著抑制了小鼠血液中的寄生虫负荷，延长了小鼠的存活时间，但是停药后血液中的寄生虫负荷迅速增加[7]。
| Cell experiment [1]: | |
Cell lines | J774 macrophages |
Preparation Method | J774 macrophages were placed simultaneously with L. donovani promastigotes over plastic coverslips inside a 24-well plate, using a ratio of 1:20 macrophages:parasites. After a 24-h incubation to ensure macrophage adhesion and parasite invasion, the wells were washed three times with PBS to remove any non-adherent macrophages and non-internalized parasites. Subsequently, DMEM medium with increasing concentrations of SQ109 (0-10μM) was added to the wells and cells were incubated for 48h, including the appropriate controls. Coverslips were washed with PBS, sealed with methanol, and stained with Giemsa. The percentage of infected cells was determined by light microscopy. |
Reaction Conditions | 0-10μM; 48h |
Applications | SQ109 inhibits the proliferation of promastigotes of L. donovani in a dose-dependent manner, a 100% inhibition of proliferation being observed at a concentration of 5μM and an almost complete inhibition of growth at a concentration of 2μM. |
| Animal experiment [2]: | |
Animal models | Female BALB/c mice |
Preparation Method | Mice were infected with T.b.brucei Lister 427 (4×104 cells) by i.p. injection. The mice were divided into groups, and drug treatment was performed for five consecutive days by starting from day 1 post-infection and administering 30mg/kg of pentamidine, or 30mg/kg of SQ109, or 100mg/kg of SQ109, respectively. Drugs were freshly prepared each day. All drugs were administered once daily for 5 days via the per os (p.o.) route. Parasitemia was evaluated daily for 2 weeks by blood collection from the mouse tail vein, and survival was monitored for 1 month. Mice showing impaired health status and/or with a parasite load of >108 cells per mL of blood were euthanized. |
Dosage form | 30, 100mg/kg; 5 days; p.o. |
Applications | SQ109 treated group (30mg/kg), the average day of survival was 8.6, which is 3.4 days of extended survival compared to the vehicle control. Increasing the dose of SQ109 to 100mg/kg showed a similar (3.6) average days of extended survival. |
References: | |
| Cas No. | 502487-67-4 | SDF | |
| 别名 | NSC 722041;SQ-109;SQ 109 | ||
| 化学名 | N'-(2-adamantyl)-N-[(2E)-3,7-dimethylocta-2,6-dienyl]ethane-1,2-diamine | ||
| Canonical SMILES | CC(=CCCC(=CCNCCNC1C2CC3CC(C2)CC1C3)C)C | ||
| 分子式 | C22H38N2 | 分子量 | 330.55 |
| 溶解度 | DMSO : ≥ 25 mg/mL (75.63 mM) | 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 | 3.0253 mL | 15.1263 mL | 30.2526 mL |
| 5 mM | 605.1 μL | 3.0253 mL | 6.0505 mL |
| 10 mM | 302.5 μL | 1.5126 mL | 3.0253 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。
Quality Control & SDS
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- Purity: >98.00%
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