| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
SSK1 targets senescent cells, which are characterized by elevated lysosomal β-galactosidase activity. The prodrug is conjugated to a galactose moiety, which is cleaved by β-galactosidase in senescent cells, releasing a cytotoxic gemcitabine metabolite. This leads to the activation of p38 MAPK and induction of apoptosis, sparing normal cells.
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| ln Vitro |
In senescent cells, SSK1 (0.5 μM; 12-72 hours) stimulates the phosphorylation levels of MKK3/MKK6 and p38 MAPK. Senescent cells are eliminated by SSK1 through the p38 MAPK signaling pathway. In senescent cells, SSK1 can cause damage to the mitochondrial DNA [1]. SSK1 (0.01-1 μM; 3 days) effectively and selectively removes β-galactosidase-positive senescent cells within a wide processing window [1].
In vitro, SSK1 selectively eliminates mouse and human senescent cells independently of senescence inducers and cell types. It induces p38 MAPK and MKK3/MKK6 phosphorylation, promotes mitochondrial DNA damage, and triggers apoptosis. The compound is activated by lysosomal β-galactosidase and shows specificity for senescent cells over normal cells. |
| ln Vivo |
In rats with lung damage, SSK1 (0.5 mg/kg; intraperitoneal injection; two days per week; for four weeks) lowers aging-related indicators and removes senescent cells [1]. SSK1 (0.5 mg/kg; 3 days every 2 weeks for 8 weeks) attenuates low-grade local and systemic inflammation, successfully clears senescent cells in various organs, and decreases senescence and age-related genetic markers in mice (20 months of age) [1].
In vivo, SSK1 has been shown to attenuate inflammation in aged or fibrotic mouse models. It selectively eliminates senescent cells, leading to a reduction in senescence-associated secretory phenotype (SASP) and improved tissue function. These studies demonstrate its potential as a senolytic therapy for age-related diseases. |
| Enzyme Assay |
The in vitro assay for SSK1 involves measuring its ability to selectively kill senescent cells. Cells are treated with the compound, and cell viability is assessed. The activation of p38 MAPK is confirmed by Western blotting. The compound's specificity for senescent cells is demonstrated by comparing its effects on senescent versus normal cells.
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: Primary mouse fibroblasts Tested Concentrations: 0.5 µM Incubation Duration: 12 hrs (hours), 24 hrs (hours), 36 hrs (hours), 48 hrs (hours), 72 hrs (hours) Experimental Results: Both p38 MAPK and MKK3/MKK6 were activated by phosphorylation in senescent cells. Cellular assays for SSK1 are performed using both senescent and normal cells. Cells are treated with SSK1, and cell viability is assessed. The induction of apoptosis and p38 MAPK phosphorylation is measured. These assays confirm its selectivity and mechanism of action. |
| Animal Protocol |
Animal/Disease Models: Mice (3-6-month-old) were subjected to transtracheal injection of Bleomycin[1]
Doses: 0.5 mg/kg Route of Administration: intraperitoneally (ip) injection ; two days every week; for four weeks Experimental Results: SSK1 Dramatically diminished the percentage of SA-β-gal-positive cells in lung by 3.8-fold compared with that in vehicle-treated lung-injured mice In vivo animal protocols for SSK1 involve administering the compound to aged or fibrotic mouse models. The compound's effects on senescent cell clearance, inflammation, and tissue function are assessed. These studies provide preclinical evidence for its senolytic activity. |
| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of SSK1 have not been characterized. It is a small molecule with a molecular weight of 788.61. The compound is typically administered in vivo, and its distribution and metabolism are not detailed. Further studies are needed to determine its ADME profile.
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| Toxicity/Toxicokinetics |
Toxicity data for SSK1 are limited. As a senolytic prodrug, it is designed to be activated in senescent cells, sparing normal cells. This reduces the risk of toxicity. However, comprehensive toxicological studies are needed. The compound is intended for research use only.
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| References | |
| Additional Infomation |
SSK1 is a β-galactosidase-targeted senolytic prodrug that selectively eliminates senescent cells. It activates p38 MAPK and induces apoptosis. The compound has shown efficacy in aged and fibrotic mouse models and is used as a research tool for studying cellular senescence and aging.
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| Molecular Formula |
C31H34F2N4O18
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|---|---|
| Molecular Weight |
788.61
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| Exact Mass |
788.183
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| CAS # |
2629250-69-5
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| PubChem CID |
162642741
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| Appearance |
White to off-white solid powder
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| LogP |
0.2
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
20
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| Rotatable Bond Count |
17
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| Heavy Atom Count |
55
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| Complexity |
1560
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| Defined Atom Stereocenter Count |
8
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| SMILES |
O(C1C=CC(COC(=O)NC2C=CN([C@H]3C([C@H](O)[C@@H](CO)O3)(F)F)C(=O)N=2)=CC=1N(=O)=O)[C@@H]1O[C@H](COC(=O)C)[C@H](OC(=O)C)[C@H](OC(=O)C)[C@H]1OC(=O)C
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| InChi Key |
DLQYTWCQXUJEML-XERWOCHESA-N
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| InChi Code |
InChI=1S/C31H34F2N4O18/c1-13(39)48-12-21-23(50-14(2)40)24(51-15(3)41)25(52-16(4)42)27(54-21)53-19-6-5-17(9-18(19)37(46)47)11-49-30(45)35-22-7-8-36(29(44)34-22)28-31(32,33)26(43)20(10-38)55-28/h5-9,20-21,23-28,38,43H,10-12H2,1-4H3,(H,34,35,44,45)/t20-,21-,23+,24+,25-,26-,27-,28-/m1/s1
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| Chemical Name |
[(2R,3S,4S,5R,6S)-3,4,5-triacetyloxy-6-[4-[[1-[(2R,4R,5R)-3,3-difluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-2-oxopyrimidin-4-yl]carbamoyloxymethyl]-2-nitrophenoxy]oxan-2-yl]methyl acetate
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 : 200 mg/mL (253.61 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (6.34 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 50.0 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: ≥ 5 mg/mL (6.34 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 50.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2681 mL | 6.3403 mL | 12.6805 mL | |
| 5 mM | 0.2536 mL | 1.2681 mL | 2.5361 mL | |
| 10 mM | 0.1268 mL | 0.6340 mL | 1.2681 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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