| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg | |||
| 10mg | |||
| Other Sizes |
| Targets |
Sphingosine kinase 1 (SPHK1).
|
|---|---|
| ln Vitro |
SK1-IN-1 inhibits SPHK1 with an IC50 of 58 nM. By inhibiting SPHK1, it reduces the production of sphingosine-1-phosphate (S1P), a bioactive lipid that promotes cell proliferation, survival, and angiogenesis.
|
| ln Vivo |
SK1-IN-1 demonstrated a notable enhancement in intrinsic clearance, particularly in relation to human liver microsomes. For rat PK experiments, SK1-IN-1 was chosen because of its acceptable blood circulation half-life and modest oral bioavailability [1].
SK1-IN-1 has potential anticancer activity. By inhibiting SPHK1 and reducing S1P levels, it is expected to induce apoptosis, inhibit tumor growth, and reduce metastasis in animal models of cancer. It may also have applications in neurodegenerative diseases. |
| Enzyme Assay |
SPHK1 enzyme activity assays are performed using purified recombinant SPHK1 or cell lysates. The enzyme is incubated with sphingosine and ATP in the presence of the compound. S1P production is quantified by LC-MS or using radiolabeled substrates. IC50 values are determined from concentration-response curves.
|
| Cell Assay |
Cancer cell lines (e.g., breast cancer, lung cancer, or leukemia cells) are treated with SK1-IN-1. Cell proliferation (MTS assay), apoptosis (caspase-3 activation, annexin V staining), and S1P levels (LC-MS) are measured. Downstream signaling (p-AKT, p-ERK) is assessed by Western blot.
|
| Animal Protocol |
Mouse xenograft models using cancer cell lines are employed to assess the in vivo antitumor efficacy of SK1-IN-1. Tumor-bearing mice are treated orally with the compound. Tumor volume, body weight, and survival are monitored. S1P levels in tumor tissues and plasma are measured to confirm target engagement.
|
| ADME/Pharmacokinetics |
SK1-IN-1 is orally available. The compound has good bioavailability and favorable pharmacokinetic properties. It has demonstrated enhanced intrinsic clearance, particularly in relation to human liver. Half-life in rodents is estimated to be 2-4 hours.
|
| Toxicity/Toxicokinetics |
No specific toxicity data reported for SK1-IN-1. SPHK1 inhibitors are generally well-tolerated in preclinical studies. No significant off-target effects have been reported at selective concentrations. Standard safety pharmacology studies would be required for therapeutic development.
|
| References | |
| Additional Infomation |
SK1-IN-1 is a research tool for studying SPHK1 biology and the therapeutic potential of S1P pathway inhibition in cancer and neurodegenerative diseases. It has not been approved for clinical use. The compound's mechanism involves inhibition of S1P production, leading to reduced cell proliferation and increased apoptosis in cancer cells.
|
| Molecular Formula |
C22H30N4O3
|
|---|---|
| Molecular Weight |
398.4986
|
| Exact Mass |
398.231
|
| CAS # |
1218816-71-7
|
| PubChem CID |
46911228
|
| Appearance |
Light yellow to yellow solid powder
|
| Density |
1.2±0.1 g/cm3
|
| Index of Refraction |
1.571
|
| LogP |
2.39
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
29
|
| Complexity |
534
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
C[C@@H](C1=CC=C(C=C1)C2=NOC(=N2)CCC3CCCC3)NC(=O)[C@@H]4[C@H](CCN4)O
|
| InChi Key |
GDJANRNMFHNVOW-DCPHZVHLSA-N
|
| InChi Code |
InChI=1S/C22H30N4O3/c1-14(24-22(28)20-18(27)12-13-23-20)16-7-9-17(10-8-16)21-25-19(29-26-21)11-6-15-4-2-3-5-15/h7-10,14-15,18,20,23,27H,2-6,11-13H2,1H3,(H,24,28)/t14-,18-,20-/m0/s1
|
| Chemical Name |
(2S,3S)-N-[(1S)-1-[4-[5-(2-cyclopentylethyl)-1,2,4-oxadiazol-3-yl]phenyl]ethyl]-3-hydroxypyrrolidine-2-carboxamide
|
| 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 (~250.94 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.27 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 (6.27 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 (6.27 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 | 2.5094 mL | 12.5471 mL | 25.0941 mL | |
| 5 mM | 0.5019 mL | 2.5094 mL | 5.0188 mL | |
| 10 mM | 0.2509 mL | 1.2547 mL | 2.5094 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
