| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Plasmodium
Human cathepsin L (IC50 = 56 nM), a cysteine protease involved in protein degradation, antigen presentation, and cancer progression. SID 26681509 is a slow-binding and slowly reversible competitive inhibitor with inhibition rate constants kon = 24,000 M-¹s-¹ and koff = 2.2 × 10-⁵ s-¹ (Ki = 0.89 nM). It shows no inhibitory activity against cathepsin G. |
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| ln Vitro |
SID 26681509 gains potency and exhibits an IC50 of 1.0 nM following a 4-hour preincubation with cathepsin L. The findings indicate that SID 26681509 functions as a slowly reversible and slowly binding competitive inhibitor. For single-step reversibility, inhibition rate constants were determined using a transient kinetic analysis to be kon = 24,000 M-1s-1 and koff = 2.2 × 10-5 s-1 (Ki = 0.89 nM). Utilizing the experimentally-derived X-ray crystal structure of papin/CLIK-148, molecular docking investigations are conducted [1]. After an hour, the IC50 values of SID 26681509 were found to range from 618 nM to 8.442 μM, indicating its inhibition of papin and cathepsins B, K, S, and V. When it comes to the serine protease cathepsin G, SID 26681509 has no inhibitory activity[1]. With an IC50 value of 0.5 μM, 26681509 inhibits the activity of cathepsin V. SID 26681509 (1-30 μM) dose-dependently inhibits TNF-α production generated by high-mobility group box 1 (HMGB1) without compromising cell viability[2].
In vitro, SID 26681509 quarterhydrate is a potent cathepsin L inhibitor (IC50=56 nM) with a Ki of 0.89 nM. It shows selectivity over cathepsin G (no inhibition). The compound inhibits the in vitro propagation of malaria parasite Plasmodium falciparum (IC50=15.4 uM) and Leishmania major (IC50=12.5 uM). It is a slow-binding, slowly reversible competitive inhibitor as determined by transient kinetic analysis. |
| ln Vivo |
Treatment with SID 26681509 dramatically increases survival in mice sepsis models and decreases liver damage during warm hepatic ischemia/reperfusion (I/R) models[2].
In vivo activity data for SID 26681509 quarterhydrate are limited. As a selective cathepsin L inhibitor with potent in vitro antiparasitic activity against P. falciparum and L. major, the compound may show efficacy in animal models of malaria or leishmaniasis. Further in vivo studies are needed to evaluate its therapeutic potential for parasitic infections. The quarterhydrate formulation improves compound stability. |
| Enzyme Assay |
Cathepsin L enzyme inhibition assay protocol: Recombinant human cathepsin L (10 nM) is pre-incubated with assay buffer (100 mM sodium acetate, pH 5.5, 5 mM DTT, 1 mM EDTA) for 10 min at 37degC. Increasing concentrations of SID 26681509 quarterhydrate (0-1000 nM) are added, followed by addition of fluorogenic substrate Z-Phe-Arg-AMC (10 uM). Fluorescence is monitored continuously (ex=380 nm, em=460 nm) for 15 min. IC50 is calculated from initial rates using non-linear regression (n=3).
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| Cell Assay |
Parasite growth inhibition assay protocol: P. falciparum (3D7 strain) is cultured in human erythrocytes at 2% hematocrit in RPMI-1640 with 0.5% Albumax. Parasites (1% parasitemia) are seeded in 96-well plates and treated with SID 26681509 quarterhydrate at concentrations of 0-100 uM for 72 hours. Parasite growth is assessed by measuring lactate dehydrogenase activity or by SYBR Green I DNA dye fluorescence. IC50 (15.4 uM) is calculated by non-linear regression from triplicate wells. For L. major, promastigotes are cultured and similarly treated.
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| Animal Protocol |
Mouse malaria model protocol (suggested): Female BALB/c mice (6-8 weeks old) are infected intraperitoneally with P. berghei (1×10⁶ infected RBCs). At 4-6 hours post-infection, mice are randomized into groups (n=5-6). SID 26681509 quarterhydrate is administered via intraperitoneal injection at 10-50 mg/kg, once daily for 4 days. Parasitemia is monitored daily by Giemsa-stained blood smears. Efficacy is assessed as percent suppression of parasitemia compared to vehicle control on day 4 post-infection.
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| ADME/Pharmacokinetics |
PK data for SID 26681509 quarterhydrate are limited. The compound has molecular weight 544.16 and good solubility in DMSO (50 mg/mL). As a small molecule, it is expected to have reasonable oral bioavailability. The quarterhydrate salt form is used to enhance stability and solubility. Pharmacokinetic parameters (half-life, Cmax, AUC) can be determined in rodent models using LC-MS/MS analysis after intravenous or oral administration.
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| Toxicity/Toxicokinetics |
Toxicology data for SID 26681509 quarterhydrate are limited. The compound is intended for research use only and not for human therapeutic applications. As a cathepsin L inhibitor, potential toxicities may include off-target effects on other cathepsin family members (cathepsin S, K, B) if selectivity is incomplete. The quarterhydrate form is stable and should be stored at -20degC for long-term storage. Standard safety precautions should be followed.
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| References |
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| Additional Infomation |
SID 26681509 quarterhydrate is a research tool compound for studying cathepsin L biology and for evaluating cathepsin L as a therapeutic target in parasitic diseases. Cathepsin L plays essential roles in the life cycle of Plasmodium and Leishmania species. The compound is a slow-binding, competitive inhibitor with high selectivity over cathepsin G. It has not entered clinical trials and is not approved for human use. Purity >97%.
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| Molecular Formula |
C27H33N5O5S.1/4H2O
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| Molecular Weight |
544.16
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| Related CAS # |
SID 26681509;958772-66-2
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| Appearance |
White to off-white solid powder
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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 :~50 mg/mL (~91.88 mM)
Ethanol :~5 mg/mL (~9.19 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (3.07 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 16.7 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8377 mL | 9.1885 mL | 18.3769 mL | |
| 5 mM | 0.3675 mL | 1.8377 mL | 3.6754 mL | |
| 10 mM | 0.1838 mL | 0.9188 mL | 1.8377 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.
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