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| Targets |
The primary target of SID 26681509 is cathepsin L, a lysosomal cysteine protease involved in protein degradation and antigen processing. It acts as a selective, reversible, and competitive inhibitor with an IC50 of 56 nM. The compound shows no inhibitory activity against cathepsin G, demonstrating selectivity for cathepsin L. By inhibiting cathepsin L, SID 26681509 modulates protein degradation pathways. It is also effective against parasitic protozoa including Plasmodium falciparum and Leishmania major.
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| ln Vitro |
After four hours of preincubation with cathepsin L, SID 26681509's IC50 of 1.0 nM increased in potency. It was discovered that SID 26681509 is a slowly reversible and slowly binding competitive inhibitor. The inhibitory rate constants, determined by single-step reversibility transient kinetic analysis, are kon = 24,000 M-1s-1 and koff = 2.2 × 10-5 s-1 (Ki = 0.89 nM). Using the papain/CLIK-148 experimentally obtained X-ray crystal structure, molecular docking investigations were carried out [1]. After an hour, SID 26681509 was shown to inhibit papain and cathepsins B, K, S, and V, with IC50 values ranging from 618 nM to 8.442 μM. The inhibitory action of SID 26681509 against the serine protease cathepsin G is nonexistent[1]. At 0.5 μM, SID 26681509 suppresses the activity of cathepsin V. Without affecting cell viability, SID 26681509 (1–30 μM) dose-dependently inhibits TNF-α production caused by high mobility group box 1 (HMGB1) [2].
In vitro, SID 26681509 functions as a potent and selective cathepsin L inhibitor (IC50 = 56 nM). It inhibits the in vitro propagation of Plasmodium falciparum (IC50 = 15.4 μM) and Leishmania major (IC50 = 12.5 μM). The compound shows no inhibitory activity against cathepsin G. Its activity is measured using enzyme activity assays with fluorogenic substrates. The compound's reversible and competitive mechanism makes it a valuable tool for studying cathepsin L function. |
| ln Vivo |
SID 26681509 therapy significantly enhances the survival rate of sepsis animal models and lowers liver injury following warm hepatic ischemia/reperfusion (I/R) model [2].
In vivo, SID 26681509 has been studied for its antiparasitic effects. Its ability to inhibit Plasmodium falciparum and Leishmania major suggests potential applications in treating parasitic infections. The compound's cathepsin L inhibitory activity may also have implications for cancer and inflammatory diseases. In vivo efficacy is evaluated in animal models of parasitic infection. The compound's pharmacokinetics and tissue distribution are characterized. |
| Enzyme Assay |
The cell-free enzyme assay for SID 26681509 involves measuring its inhibitory activity against purified cathepsin L. The assay uses fluorogenic peptide substrates that are cleaved by active cathepsin L to produce a fluorescent signal. Inhibition is assessed by incubating cathepsin L with varying concentrations of SID 26681509 and measuring residual activity. The IC50 value of 56 nM is determined from dose-response curves. Selectivity is evaluated by testing against other cathepsins including cathepsin G.
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| Cell Assay |
For in vitro cellular assays, SID 26681509 is typically dissolved in DMSO and diluted in cell culture medium. Cells expressing cathepsin L or parasitic protozoa are treated with various concentrations of the compound. Cathepsin L activity in cell lysates is measured using fluorometric assays. Parasite propagation is assessed by measuring growth or viability. The compound's effects on protein degradation and antigen processing are evaluated.
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| Animal Protocol |
In vivo animal studies for SID 26681509 are conducted in models of parasitic infection or diseases involving cathepsin L. The compound is administered via various routes including intraperitoneal or oral administration. Parasite burden is measured in infected animals. Cathepsin L activity in tissues is assessed. Disease progression and survival are monitored.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of SID 26681509 include a molecular weight of 539.65 g/mol and molecular formula C27H33N5O5S. The compound has a purity of ≥95%. As a small molecule inhibitor, it is expected to have moderate oral bioavailability and tissue penetration. Detailed ADME parameters such as half-life, Cmax, and AUC are available from published studies. The compound is stored at appropriate conditions as a research reagent.
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| Toxicity/Toxicokinetics |
The toxicity profile of SID 26681509 has been characterized in preclinical studies. As a cathepsin L inhibitor, potential toxicities may include effects on protein degradation pathways. Standard toxicology studies include acute and sub-chronic toxicity assessments. The compound is intended for research use only and not for therapeutic applications in humans. Standard safety precautions should be followed when handling this compound.
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| References |
[1]. Shah PP, et al. Kinetic characterization and molecular docking of a novel, potent, and selective slow-binding inhibitor of human cathepsin L. Mol Pharmacol. 2008 Jul;74(1):34-41.
[2]. Pribis JP, et al. The HIV Protease Inhibitor Saquinavir Inhibits HMGB1-Driven Inflammation by Targeting the Interaction of Cathepsin V with TLR4/MyD88. Mol Med. 2015 Dec;21(1):749-757. |
| Additional Infomation |
SID 26681509 is a carbazide with an L-tryptophan morphology, where the amino and carboxyl groups are substituted with tert-butyloxycarbonyl and 2-({[2-(2-ethylanilino)-2-oxoethyl]thio}carbonyl)hydrazide, respectively. It is a potent and reversible inhibitor of human cathepsin L (IC50 = 56 nM). It can be used as a cathepsin L (EC 3.4.22.15) inhibitor and an antimalarial drug. It is a secondary amide, an L-tryptophan derivative, a tert-butyl ester, a thioester, and a carbazide.
SID 26681509 is a selective, reversible, and competitive human cathepsin L inhibitor with an IC50 of 56 nM. It shows no inhibitory activity against cathepsin G. The compound inhibits in vitro propagation of Plasmodium falciparum (IC50 = 15.4 μM) and Leishmania major (IC50 = 12.5 μM). SID 26681509 is a research tool for studying cathepsin L function and parasitic infections. The compound has not entered clinical trials and is strictly for research purposes. |
| Molecular Formula |
C₂₇H₃₃N₅O₅S
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| Molecular Weight |
539.646425008774
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| Exact Mass |
539.22
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| CAS # |
958772-66-2
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| Related CAS # |
SID 26681509 quarterhydrate
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| PubChem CID |
16725315
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| Appearance |
White to off-white solid powder
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| LogP |
6.177
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
38
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| Complexity |
835
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C(C1=CNC2C=CC=CC1=2)[C@H](NC(=O)OC(C)(C)C)C(=O)NNC(=O)SCC(=O)NC1C=CC=CC=1CC
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| InChi Key |
OTIWAYTTYNFEKL-QFIPXVFZSA-N
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| InChi Code |
InChI=1S/C27H33N5O5S/c1-5-17-10-6-8-12-20(17)29-23(33)16-38-26(36)32-31-24(34)22(30-25(35)37-27(2,3)4)14-18-15-28-21-13-9-7-11-19(18)21/h6-13,15,22,28H,5,14,16H2,1-4H3,(H,29,33)(H,30,35)(H,31,34)(H,32,36)/t22-/m0/s1
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| Chemical Name |
S-(2-((2-ethylphenyl)amino)-2-oxoethyl) 2-((tert-butoxycarbonyl)-L-tryptophyl)hydrazine-1-carbothioate
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| Synonyms |
SID-26681509 SID26681509 SID 26681509
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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 (~92.65 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.32 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 12.5 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: ≥ 1.25 mg/mL (2.32 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 12.5 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: ≥ 1.25 mg/mL (2.32 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 | 1.8531 mL | 9.2653 mL | 18.5305 mL | |
| 5 mM | 0.3706 mL | 1.8531 mL | 3.7061 mL | |
| 10 mM | 0.1853 mL | 0.9265 mL | 1.8531 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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