| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg | |||
| Other Sizes |
| Targets |
SPL-707 targets signal peptide peptidase-like 2a (SPPL2a), an intramembrane protease that cleaves type II transmembrane proteins. SPPL2a plays a critical role in B cell and dendritic cell function, making it a therapeutic target for autoimmune diseases. SPL-707 is a selective inhibitor with an IC50 of 77 nM for hSPPL2a.
|
|---|---|
| ln Vitro |
SPL-707 (compound 40) inhibits mouse SPPL2a (IC50=0.18 μM), rat SPPL2a (IC50=0.056 μM), human SPPL2a (IC50=0.16 μM), and human SPPL2b (IC50=0.43 μM), according to high-content imaging. )(HCA)[1].
SPL-707 is an effective and selective SPPL2a inhibitor with an IC50 of 77 nM for hSPPL2a. It shows adequate selectivity against the closely related enzymes γ-secretase and SPP. The compound is orally active and has a good pharmacokinetic profile in mouse and rat. |
| ln Vivo |
SPL-707 (Compound 40; 3–30 mg/kg; oral; bid; for 11 days) reduces bone marrow dendritic cells and B cells but does not change gamma-secretase activity [1]. The AUC of SPL-707 is 8787 h·nM, and its CL is 6 mL/min·kg (3 mg/kg orally, 1 mg/kg intravenously) [1]. The spleen of female Lewis rats is totally inhibited from processing CD74/p8 by SPL-707 (1, 3 mg/kg; bid; first dose at 0 hours, second dose at 8 hours) [1].
SPL-707 is orally active and has a good pharmacokinetic profile in mouse and rat. As a SPPL2a inhibitor, it has potential for autoimmune diseases research by targeting B cells and dendritic cells. Specific efficacy data in autoimmune disease models are not extensively detailed in standard reference sources. |
| Enzyme Assay |
SPL-707's inhibition of SPPL2a can be assessed using in vitro enzyme activity assays. Recombinant human SPPL2a is incubated with a fluorogenic substrate in the presence of varying concentrations of SPL-707. The cleavage of the substrate is measured by fluorescence detection, and IC50 values are calculated from dose-response curves. Selectivity against γ-secretase and SPP is assessed using similar assays with those enzymes.
|
| Cell Assay |
The cellular activity of SPL-707 is evaluated in B cell or dendritic cell models. Cells are treated with increasing concentrations of SPL-707, and SPPL2a-mediated substrate cleavage is measured by Western blot or ELISA. The effect of SPPL2a inhibition on B cell proliferation, differentiation, and cytokine production is assessed. Cell viability is monitored to ensure specificity.
|
| Animal Protocol |
Animal/Disease Models: Female SD (SD (Sprague-Dawley)) rat [1]
Doses: 3 mg/kg orally, 1 mg/kg intravenously (iv) (iv)(iv) (pharmacokinetic/PK/PK analysis) Route of Administration: Oral or intravenous (iv) (iv)injection Experimental Results:CL is 6 mL/min• kg, CL is 6 mL/min·kg, AUC is 8787 h·nM. SPL-707 is administered orally in mouse and rat models for pharmacokinetic and pharmacodynamic studies. In autoimmune disease models (e.g., experimental autoimmune encephalomyelitis or lupus models), SPL-707 would be given at various doses. B cell and dendritic cell function, autoantibody levels, and disease severity would be assessed. |
| ADME/Pharmacokinetics |
SPL-707 has a molecular formula of C27H28FN5O4 and a molecular weight of 505.54 g/mol. It is orally active and has a good pharmacokinetic profile in mouse and rat. The powder can be stored at -20°C for 3 years, and in solvent at -80°C for 1 year.
|
| Toxicity/Toxicokinetics |
The toxicity profile of SPL-707 is not extensively documented. As a SPPL2a inhibitor targeting B cells and dendritic cells, potential adverse effects may include immunosuppression. Specific LD50 values and organ-specific toxicity data are not readily available.
|
| References | |
| Additional Infomation |
SPL-707 (CAS# 2195361-33-0) is the first orally active, selective SPPL2a inhibitor. It has an IC50 of 77 nM for hSPPL2a and shows selectivity against γ-secretase and SPP. SPL-707 has potential for autoimmune diseases research by targeting B cells and dendritic cells.
|
| Molecular Formula |
C27H28FN5O4
|
|---|---|
| Molecular Weight |
505.540729522705
|
| Exact Mass |
505.212
|
| CAS # |
2195361-33-0
|
| PubChem CID |
134691740
|
| Appearance |
White to off-white solid powder
|
| LogP |
1.9
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
37
|
| Complexity |
968
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
FC1=CN=C(C)C(=C1)NC(C[C@H](C(N[C@H]1C2C=CC=CC=2C(N2CC3(CN2C1=O)CC3)=O)=O)C1CC1)=O
|
| InChi Key |
WLQXBRYTQYYCMW-REWPJTCUSA-N
|
| InChi Code |
InChI=1S/C27H28FN5O4/c1-15-21(10-17(28)12-29-15)30-22(34)11-20(16-6-7-16)24(35)31-23-18-4-2-3-5-19(18)25(36)32-13-27(8-9-27)14-33(32)26(23)37/h2-5,10,12,16,20,23H,6-9,11,13-14H2,1H3,(H,30,34)(H,31,35)/t20-,23-/m0/s1
|
| Chemical Name |
(2S)-2-cyclopropyl-N-[(6S)-5,11-dioxospiro[3,6-dihydro-1H-pyrazolo[1,2-b][2,3]benzodiazepine-2,1'-cyclopropane]-6-yl]-N'-(5-fluoro-2-methylpyridin-3-yl)butanediamide
|
| Synonyms |
SPL707; SPL 707; SPL-707
|
| 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 |
| 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 : ~100 mg/mL (~197.81 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (9.89 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 (9.89 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 | 1.9781 mL | 9.8904 mL | 19.7808 mL | |
| 5 mM | 0.3956 mL | 1.9781 mL | 3.9562 mL | |
| 10 mM | 0.1978 mL | 0.9890 mL | 1.9781 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
