| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg | |||
| 100mg | |||
| Other Sizes |
| Targets |
Ki: 31 nM (LSD1)[1] IC50: 13 nM (LSD1)[1]
Lysine-specific demethylase 1 (LSD1/KDM1A). Seclidemstat is a noncompetitive, reversible inhibitor with biochemical activity in the low nanomolar range (Ki ~31 nM, IC50 ~13 nM). By inhibiting LSD1, it increases histone methylation (particularly H3K4me2 and H3K9me2), reversing the transcriptional activity of oncogenic FET fusion proteins such as EWSR1::FLI1 in Ewing sarcoma. |
|---|---|
| ln Vitro |
For COV434, BIN67, SCCOHT-1, TOV21G, SKOV3, A427, H522, A549, H1299, G401, G402, and HCC15 cells, seclidemstat (72 hours) mesylate suppresses SWI/SNF-mutation-dependent tumor cell growth with an IC50 ranging from 0.013 to 2.819 μM[2]. In the SCCOHT cell lines (SCCOHT-1, BIN67, and COV434 cells), seclidemstat (72 hours) mesylate stimulates the development of endogenous retroviruses (ERVs) and activates the IFNβ pathway[2]. In the SCCOHT COV 434 pIND 20 BRG1-2.7 cell line, seclidemstat (3 μM) mesylate increases PD-L1 expression[2].
In vitro, seclidemstat inhibits LSD1 enzymatic activity, leading to increased histone methylation. It has potent cytotoxicity against both FET-rearranged and other fusion-positive sarcoma cell lines, including Ewing sarcoma, desmoplastic small round cell tumor, clear cell sarcoma, myxoid liposarcoma, and fusion-positive rhabdomyosarcoma. Seclidemstat recapitulates much of the transcriptional activity of the related LSD1 inhibitor SP-2509 in Ewing sarcoma. Widespread transcriptional changes are seen in all tested cell lines, including reversal of FET fusion transcriptional signatures for EWSR1::WT1, EWSR1::ATF1, and EWSR1::ERG. It promotes antitumor immunity and inhibits viral DNA replication. |
| ln Vivo |
In vivo, seclidemstat has shown antitumor activity in mouse models of Ewing sarcoma and ovarian cancer. It promotes antitumor immunity and inhibits tumor growth. The compound is currently being evaluated in clinical trials for Ewing sarcoma and related FET-rearranged tumors (NCT03600649 and NCT05266196), as well as myelodysplastic syndrome and chronic myelomonocytic leukemia (NCT04734990). Though novel inhibitors are unlikely to display single-agent efficacy in the clinic, seclidemstat remains a promising new treatment strategy for patients with FET-rearranged and other fusion-positive sarcomas.
|
| Enzyme Assay |
LSD1 enzymatic activity assay: Recombinant LSD1 (10-20 nM) is incubated with a biotinylated histone H3 peptide substrate (H3K4me2, 0.5-1 uM) and varying concentrations of seclidemstat (0.01-10,000 nM) in assay buffer (50 mM Tris-HCl pH 7.4, 0.1 mg/mL BSA, 1 mM TCEP) for 30-60 minutes at 37degC. Demethylation of the substrate is detected by time-resolved fluorescence resonance energy transfer (TR-FRET) or AlphaLISA using an antibody specific for demethylated H3K4 (H3K4me0) or by measuring formaldehyde production using a fluorescent probe. IC50 values are calculated from dose-response curves.
|
| Cell Assay |
Cellular biomarker and proliferation assays: Cancer cell lines (e.g., Ewing sarcoma cells such as A673 or SK-ES-1) are treated with seclidemstat (0.01-10 uM) for 48-72 hours. Histone methylation status (H3K4me2, H3K9me2) is assessed by Western blot to confirm target engagement. Cell viability is measured using CellTiter-Glo or MTT assays. Transcriptomic effects are assessed by RNA sequencing to evaluate reversal of FET fusion transcriptional signatures.
|
| Animal Protocol |
Mouse xenograft models: Immunodeficient mice bearing human tumor xenografts (e.g., Ewing sarcoma, A673 or SK-ES-1 cells) are treated with seclidemstat (50-100 mg/kg, orally or intraperitoneally, daily) for 14-21 days. Tumor growth inhibition is measured, and tumors are harvested for pharmacodynamic analysis (histone methylation, gene expression by qRT-PCR or RNA-seq) and immunohistochemistry (Ki-67, cleaved caspase-3).
|
| ADME/Pharmacokinetics |
Seclidemstat is orally bioavailable with a favorable pharmacokinetic profile. In preclinical studies, it shows good oral absorption, moderate half-life, and adequate exposure to achieve target inhibition. Detailed PK parameters (Cmax, AUC, t½) are available from clinical trial data but are not publicly disclosed in full.
|
| Toxicity/Toxicokinetics |
In preclinical studies, seclidemstat has been well-tolerated at therapeutic doses. Common adverse effects observed in clinical trials may include fatigue, gastrointestinal effects, and hematological changes, typical of epigenetic inhibitors. Phase 1 trials are ongoing to evaluate safety, tolerability, and optimal dosing.
|
| References |
|
| Additional Infomation |
See also: Seclidemstat (comment moved to).
Seclidemstat mesylate is an investigational drug that has been studied in Phase 1 clinical trials for Ewing sarcoma and other cancers. It has not received FDA approval. Also known as SP-2577. Clinical trials include NCT03600649 (Ewing sarcoma), NCT05266196, and NCT04734990 (MDS/CMML). It is an orally administered targeted agent under investigation as a single agent and in combination with topotecan and cyclophosphamide. |
| Molecular Formula |
C21H27CLN4O7S2
|
|---|---|
| Molecular Weight |
547.044681787491
|
| Exact Mass |
546.1
|
| CAS # |
2044953-70-8
|
| Related CAS # |
Seclidemstat;1423715-37-0
|
| PubChem CID |
135565032
|
| Appearance |
Off-white to light yellow solid powder
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
35
|
| Complexity |
826
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
ClC1C=CC(=C(C=1)/C(/C)=N/NC(C1=CC=CC(=C1)S(N1CCN(C)CC1)(=O)=O)=O)O.S(C)(=O)(=O)O
|
| InChi Key |
JIPBQMGGMHCGBW-CWUUNJJBSA-N
|
| InChi Code |
InChI=1S/C20H23ClN4O4S.CH4O3S/c1-14(18-13-16(21)6-7-19(18)26)22-23-20(27)15-4-3-5-17(12-15)30(28,29)25-10-8-24(2)9-11-25;1-5(2,3)4/h3-7,12-13,26H,8-11H2,1-2H3,(H,23,27);1H3,(H,2,3,4)/b22-14+;
|
| Chemical Name |
N-[(E)-1-(5-chloro-2-hydroxyphenyl)ethylideneamino]-3-(4-methylpiperazin-1-yl)sulfonylbenzamide;methanesulfonic acid
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : 53.33 mg/mL (97.49 mM)
H2O : < 0.1 mg/mL |
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8280 mL | 9.1401 mL | 18.2802 mL | |
| 5 mM | 0.3656 mL | 1.8280 mL | 3.6560 mL | |
| 10 mM | 0.1828 mL | 0.9140 mL | 1.8280 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
