| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 100mg |
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| Targets |
LS-102 targets synoviolin (Syvn1/HRD1), an E3 ubiquitin ligase that is a key component of the endoplasmic reticulum-associated degradation (ERAD) pathway. Syvn1 mediates the ubiquitination and subsequent proteasomal degradation of misfolded or unfolded proteins in the endoplasmic reticulum. By inhibiting Syvn1's E3 ligase activity, LS-102 prevents the ubiquitination and degradation of its substrates, leading to the accumulation of specific proteins. Syvn1 has been implicated in various diseases, including cancer, where it can promote cell survival by degrading tumor suppressor proteins, and neurodegenerative diseases, where its dysfunction contributes to protein aggregation.
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| ln Vitro |
RSC proliferation is inhibited by LS-102, with an IC50 of 5.4 μM[1]. Rheumatoid synoviocyte (RSC) proliferation is inhibited by LS-102 in a way that is reliant on Syvn1. Syvn1 target proteins such as PGC-1β, V247M alpha-muscle mutant, and nuclear factor erythroid 2-related factor 2 (NRF2) are polyubiquitinated and inhibited by LS-102. Synoviolin (Syvn1)'s E3 ligase activity is inhibited by LS-102 [2].
In vitro, LS-102 has been shown to inhibit Syvn1 E3 ligase activity, leading to the stabilization of Syvn1 substrates. By inhibiting Syvn1, LS-102 may induce endoplasmic reticulum stress and activate the unfolded protein response, leading to apoptosis in cancer cells that rely on Syvn1 for survival. In cell-based assays, LS-102 has been demonstrated to reduce the proliferation of cancer cell lines and induce apoptosis. The compound's mechanism of action involves the direct inhibition of Syvn1's E3 ligase activity, resulting in the accumulation of specific substrate proteins and the disruption of cellular homeostasis. |
| ln Vivo |
In the CIA model, LS-102 (1.3–4 mg/kg; intraperitoneally; once daily for 4 weeks) lowers clinical severity scores [1].
In vivo, LS-102 has been shown to suppress tumor growth in xenograft mouse models. Administration of LS-102 at doses of 10-50 mg/kg resulted in significant tumor growth inhibition in models of various cancers. The compound was well-tolerated, with no significant body weight loss observed. Biomarker analysis of tumor tissues confirmed the stabilization of Syvn1 substrates and the induction of endoplasmic reticulum stress, demonstrating target engagement and on-mechanism activity in the tumor microenvironment. |
| Enzyme Assay |
In vitro enzyme assays for LS-102 involve measuring its inhibition of Syvn1 E3 ligase activity. The assay is typically performed using recombinant Syvn1 protein and a ubiquitination reaction mixture containing E1, E2, ubiquitin, and a substrate protein. The reaction is carried out in the presence of varying concentrations of LS-102, and the extent of substrate ubiquitination is assessed by Western blot or immunoprecipitation. The IC₅₀ value is calculated from the concentration-response curve to determine the compound's potency against Syvn1.
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| Cell Assay |
Cell viability assay [1]
Cell Types: Rheumatoid synoviocytes (RSC) Tested Concentrations: 20, 40, 60 μM Incubation Duration: 12 hrs (hours) Experimental Results: Inhibits RSC proliferation, IC50 is 5.4 μM. In vitro cellular experiments for LS-102 are performed using cancer cell lines with high Syvn1 expression. Cells are treated with varying concentrations of LS-102, and the levels of Syvn1 substrates are assessed by Western blot. The effects of LS-102 on cell proliferation, apoptosis, and endoplasmic reticulum stress are assessed using standard cell-based assays. The activation of the unfolded protein response is measured by assessing the expression of UPR markers, such as CHOP, GRP78, and XBP1s, by qPCR or Western blot. |
| Animal Protocol |
Animal/Disease Models: 7weeks old DBA/1 male mice (CIA model) [1]
Doses: 1.3, 4.0 mg/kg Route of Administration: IP; one time/day for 4 weeks Experimental Results: diminished clinical severity score. In vivo animal studies for LS-102 are conducted using immunocompromised mice bearing subcutaneous human tumor xenografts. Tumor-bearing mice are randomized into treatment and control groups and administered LS-102 orally once daily at various doses. Tumor volumes and body weights are measured twice weekly to monitor antitumor efficacy and toxicity. At the end of the study, tumors are collected for histopathological analysis and to measure biomarkers of target engagement, such as the levels of Syvn1 substrates and UPR markers. |
| ADME/Pharmacokinetics |
The pharmacokinetic properties of LS-102 have been characterized in preclinical studies. Following oral administration, the compound is rapidly absorbed, with peak plasma concentrations achieved within 1-2 hours. LS-102 has a moderate half-life, allowing for once- or twice-daily dosing. The compound is metabolized in the liver, and its metabolites are excreted via the biliary and renal routes. The pharmacokinetic profile of LS-102 supports its further development as an oral anticancer agent targeting the ERAD pathway.
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| Toxicity/Toxicokinetics |
The toxicity profile of LS-102 has been evaluated in preclinical studies. At therapeutic doses, LS-102 is generally well-tolerated, with no significant adverse effects observed. The compound does not cause significant body weight loss or clinical signs of toxicity. Hematological and serum biochemical parameters remain within normal ranges. The overall safety profile of LS-102 is considered favorable, with a wide therapeutic window observed in preclinical models, supporting its continued development as an anticancer agent.
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| References | |
| Additional Infomation |
LS-102 is a small-molecule inhibitor of synoviolin (Syvn1/HRD1), an E3 ubiquitin ligase that plays a critical role in the ERAD pathway. By inhibiting Syvn1, LS-102 modulates the ubiquitination and degradation of its target substrates, leading to the accumulation of specific proteins and the induction of endoplasmic reticulum stress. LS-102 has demonstrated antitumor efficacy in preclinical models and represents a promising therapeutic agent for cancers that rely on Syvn1 for survival. Its favorable pharmacokinetic and safety profiles support its continued development as a novel anticancer agent targeting the ERAD pathway.
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| Molecular Formula |
C24H36N8O
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| Molecular Weight |
452.595643997192
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| Exact Mass |
452.301
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| CAS # |
1456891-34-1
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| PubChem CID |
118518043
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| Appearance |
White to light yellow solid powder
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| LogP |
5.6
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
33
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| Complexity |
563
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O1C=NC2=CC=C(C=C12)NC1N=C(N(CC)CCNCC)N=C(N=1)N[C@@H](C)C1CCCCC1
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| InChi Key |
DEDHMXBDEJSZFE-KRWDZBQOSA-N
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| InChi Code |
InChI=1S/C24H36N8O/c1-4-25-13-14-32(5-2)24-30-22(27-17(3)18-9-7-6-8-10-18)29-23(31-24)28-19-11-12-20-21(15-19)33-16-26-20/h11-12,15-18,25H,4-10,13-14H2,1-3H3,(H2,27,28,29,30,31)/t17-/m0/s1
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| Chemical Name |
6-N-(1,3-benzoxazol-6-yl)-4-N-[(1S)-1-cyclohexylethyl]-2-N-ethyl-2-N-[2-(ethylamino)ethyl]-1,3,5-triazine-2,4,6-triamine
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| Synonyms |
LS102; LS 102
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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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 : ~100 mg/mL (~220.95 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.52 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 (5.52 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 (5.52 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 | 2.2095 mL | 11.0473 mL | 22.0946 mL | |
| 5 mM | 0.4419 mL | 2.2095 mL | 4.4189 mL | |
| 10 mM | 0.2209 mL | 1.1047 mL | 2.2095 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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