SPL-707 |
| カタログ番号GC31854 |
SPL-707 は、hSPPL2a の IC50 が 77 nM である、経口活性の選択的シグナルペプチドペプチダーゼ様 2a (SPPL2a) 阻害剤です。
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 2195361-33-0
Sample solution is provided at 25 µL, 10mM.
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SPL-707 is a potent, selective and orally available signal peptide peptidase-like 2a (SPPL2a) inhibitor with an IC50 of 80 nM.
SPL-707 shows 25-fold selectivity over SPP with an IC50 of 3.7 μM and some preference for SPPL2a over SPPL2b with a 3-fold selectivity, comparing IC50 values generated with comparable assay formats for the different proteases[1].
SPL-707 significantly inhibits processing of the SPPL2a substrate CD74/p8 fragment in rodents at doses ≤10 mg/kg b.i.d. po. Oral dosing of SPL-707 for 11 days at ≥10 mg/kg b.i.d. recapitulates the phenotype seen in Sppl2a knockout (ko) and ENU mutant mice (reduced number of specific B cells and myeloid dendritic cells)[1].
[1]. Velcicky J, et al. Discovery of the First Potent, Selective, and Orally Bioavailable Signal Peptide Peptidase-Like 2a (SPPL2a) Inhibitor Displaying Pronounced Immunomodulatory Effects In Vivo. J Med Chem. 2018 Feb 8;61(3):865-880.
Cell experiment: | DNA vectors encoding human Notch1-VP16-Gal4 fusion protein and a Gal4-luciferase reporter for the γ-secretase RGA, or human SPPL2a, VP16-TNFa(aa1-76)-NTF substrate, and the Gal4-luciferase reporter plasmid for the SPPL2a RGA, are transiently transfected in HEK293 cells using FuGENE. After transfection, the cell suspensions are diluted and distributed to white solid 384-well plate at 10000 cells/50 μL/well. After 3 h, 200 nL of SPL-707 in DMSO is stamped into the wells in concentration response covering final inhibitor concentrations of 10 μM to 0.3 nM in triplicate. Subsequently, plates are incubated for 24 h at 37°C, 5% CO2 in a humidified incubator before the addition of 30 μL Bright Glo. After incubation for 5 min at rt, luminescence is measured and IC50 values are determined by plotting compound concentration vs normalized luminescence values[1]. |
Animal experiment: | Rats[1]Female Lewis rats receive SPL-707 (1, 3, 10, and 30 mg/kg b.i.d.; first dose at 0 h, second dose at 8 h). Then 16 h after the second dose (24 h in total), inhibition of SPPL2a is assessed by measuring CD74/p8 accumulation in blood and splenocyte extracts by Western blot analysis[1].Mice[1] Mice receive single oral doses of 150 mg/ kg 31 or 1, 3, 10, and 30 mg/kg 40. Then 16 h after dosing, inhibition of SPPL2a is assessed by measuring CD74/p8 accumulation in splenocyte lysates by Western blot analysis[1]. |
References: [1]. Velcicky J, et al. Discovery of the First Potent, Selective, and Orally Bioavailable Signal Peptide Peptidase-Like 2a (SPPL2a) Inhibitor Displaying Pronounced Immunomodulatory Effects In Vivo. J Med Chem. 2018 Feb 8;61(3):865-880. | |
| Cas No. | 2195361-33-0 | SDF | |
| Canonical SMILES | CC1=C(NC(C[C@@H](C2CC2)C(N[C@@H]3C(N(CC4(CC4)C5)N5C(C6=C3C=CC=C6)=O)=O)=O)=O)C=C(F)C=N1 | ||
| Formula | C27H28FN5O4 | M.Wt | 505.54 |
| 溶解度 | DMSO : 100 mg/mL (197.81 mM; Need ultrasonic) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
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 | 0.989 mL | 1.9781 mL |
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- Purity: >99.00%
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