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Purity: ≥98%
SQ109 (NSC-722041) is an antituberculosis drug which is currently in advanced clinical trials for the treatment of drug-susceptible and drug-resistant tuberculosis, it is a novel, potent and selective inhibitor of the trypomastigote form of the parasite with IC50 for cell killing of 50±8 nM. SQ109 showed activity against both drug susceptible and Multi-drug-resistant tuberculosis bacteria, including Extensively drug-resistant tuberculosis strains. In preclinical studies SQ109 enhanced the activity of anti-tubercular drugs isoniazid and rifampin and reduced by >30% the time required to cure mice of experimental TB. SQ109 may also have potential as a drug lead against Chagas disease.
| Targets |
Trypanosoma
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|---|---|
| ln Vitro |
With a selectivity index of approximately 10 to 20, SQ109 also inhibits clinically relevant intracellular amastigotes (IC50, ~0.5 to 1 μM) and extracellular epimastigotes (IC50, 4.6±1 μM). SQ109 performs poorly in an assay measuring hemolysis of red blood cells (EC50, ~80 μM). Furthermore, as shown by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and light microscopy (LMC), SQ109 significantly alters the ultrastructural characteristics of all three life cycle forms[1].
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| ln Vivo |
For 28 days, mice given SQ109 orally (0.1–25 mg/kg daily) showed dose-dependent reductions in lung and spleen mycobacterial loads, which were similar to those of EMB given daily at 100 mg/kg, though less effective than isoniazid (INH) given daily at 25 mg/kg. After a single administration, the pharmacokinetic profiles of SQ109 in mice revealed a Cmax of 1038 for intravenous (i.v.) and 135 ng/mL for oral administration, along with an oral Tmax of 0.31 hours.Regarding SQ109, the elimination t1/2 is 3.5 (i.v.) and 5.2 h (p.o.). Oral bioavailability amounts to 4% [2]. Dogs have a significantly larger volume of distribution for SQ109 than rats do (7-8 h, mean 7.4 h), indicating that dogs have a longer terminal half-life (t1/2) of SQ109. It has been found that SQ109 has an oral bioavailability of 12% in rats and 5% in dogs[3].
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| Cell Assay |
SQ109 (2.5–20 μM) is applied to the LLC-MK2 cells, and they are then incubated for 96 hours at 37°C. To the untreated samples, fresh RPMI 1640 medium containing 10% FBS is added as a control. The MTS/PMS test is used to assess toxicity. Based on its activities against the trypomastigote and intracellular amastigote forms of T.cruzi, SQ109's selectivity index is calculated as the ratio of the parasite's 50% lysing concentration (LC50) or IC50 to the 50% cytotoxic concentration (CC50) of mammalian cells. Every experiment is run in duplicate. Three or more experiments yield the means[1].
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| Animal Protocol |
Mice [2]
Eight-week-old female C57BL/6 mice are utilized. Twenty days after inoculation, mice are given oral doses of INH (25 mg/kg), ethambutol (EMB) (100 mg/kg), and SQ109 (0.1, 10 and 25 mg/kg). Mice infected but untreated control groups are euthanized either at the start of therapy (early controls) or at the conclusion of the treatment period. Every group consists of six mice. Four weeks after the start of treatment, the mice receive chemotherapy five days a week until they die. Weighing and aseptic removal of the lungs and spleen are performed.Two milliliters of sterile PBS containing 0.05% Tween-80 are used to homogenize the organs. After being diluted ten times in PBS, homogenate samples from distinct tissues are plated on 7H10 agar plates. Before calculating CFU, inoculated dishes are incubated for three weeks at 37°C in room temperature. A logarithmic scale is used to convert viable counts, and readings are adjusted to reflect totals for all organs. The survival rate and the mean number of CFU in mouse organs are used to evaluate the degree of infection and the efficacy of the treatments. |
| References |
| Molecular Formula |
C22H38N2
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|---|---|
| Molecular Weight |
330.55
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| Exact Mass |
330.30
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| Elemental Analysis |
C, 79.94; H, 11.59; N, 8.47
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| CAS # |
502487-67-4
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| Appearance |
Oily liquid
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| SMILES |
C/C(CC/C=C(C)\C)=C\CNCCNC1[C@H]2C[C@@H]3C[C@H](C2)CC1C3
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| InChi Key |
JFIBVDBTCDTBRH-WUROFCERSA-N
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| InChi Code |
InChI=1S/C22H38N2/c1-16(2)5-4-6-17(3)7-8-23-9-10-24-22-20-12-18-11-19(14-20)15-21(22)13-18/h5,7,18-24H,4,6,8-15H2,1-3H3/b17-7+/t18-,19+,20-,21?,22?
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| Chemical Name |
N1-((1r,5R,7S)-adamantan-2-yl)-N2-((E)-3,7-dimethylocta-2,6-dien-1-yl)ethane-1,2-diamine
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| Synonyms |
SQ109; SQ-109; SQ 109; NSC 722041; NSC-722041; NSC722041.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ ~25 mg/mL (~75.63 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.56 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.56 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.56 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0253 mL | 15.1263 mL | 30.2526 mL | |
| 5 mM | 0.6051 mL | 3.0253 mL | 6.0505 mL | |
| 10 mM | 0.3025 mL | 1.5126 mL | 3.0253 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 Effects of SQ109 on the proton motive force (PMF) in digitonin-permeabilized T. cruzi.
Effects of 75 nM SQ109 on T. cruzi trypomastigotes, as observed by scanning electron microscopy.
TEM images of intracellular amastigotes treated with SQ109 or SQ109 plus posaconazole for 96 h.Antimicrob Agents Chemother. 2015 Apr;59(4):1950-61. |
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 Effects of SQ109 on trypomastigotes and red blood cells.
SQ109 binds to the SQS active site.Antimicrob Agents Chemother. 2015 Apr;59(4):1950-61. |
 SQ109 effects on epimastigotes. (A) Effects of various concentrations of SQ109, added at 24 h, on the growth of T. cruzi epimastigotes (Y strain, TcII) treated with SQ109 for 120 h at 28°C. The parasites were cultured in the absence (control) or presence of SQ109 (from 0.5 to 10 μM).
Effects of SQ109 on amastigotes, and synergy with posaconazole. |
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