| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
BML-258 HCl targets sphingosine kinase 1 (SPHK1), the enzyme responsible for phosphorylating sphingosine to sphingosine-1-phosphate (S1P). It is an isozyme-specific competitive inhibitor with a Ki of 10 µM. The compound does not inhibit SPHK2 or a range of other kinases including PKCα, PKCδ, PKA, AKT1, ERK1, EGFR, CDK2, IKKβ, and CamK2β. This selectivity makes it a valuable tool for studying SPHK1-specific functions.
|
|---|---|
| ln Vitro |
In HCT116 cells and HCT116 cells harboring TP53-deficient tumors, SK1-I (0-10 μM; 24 hours) attenuates cancer cell proliferation and survival in a TP53-dependent way [2]. In HCT116 cells, SK1-I (0–20 μM; 12 hours) causes more CASP3 cleavage than in HCT116 cells without TP53, which is indicative of apoptosis [2].
In vitro, SK1-I (BML-258) attenuates cancer cell proliferation and survival in a TP53-dependent manner. In HCT116 cells, treatment with SK1-I (0-10 µM; 24 hours) reduces cancer cell growth. At concentrations of 0-20 µM for 12 hours, SK1-I induces greater CASP3 cleavage in HCT116 cells compared to TP53-null HCT116 cells, indicating apoptosis induction. The compound enhances autophagy and exhibits antitumor effects in various cancer cell models. |
| ln Vivo |
Intravenous anandamide at dosages of 1 and 10 mg/kg considerably lowers hypotensive reactions [3].
In vivo, intravenous administration of anandamide at doses of 1 and 10 mg/kg significantly reduces hypotensive responses. In a separate study, male C57BL/6 mice (24 ± 3.5 g) received SK1-I at 75 mg/kg via intraperitoneal injection, and baseline mean arterial blood pressure was measured 24 hours later. The compound significantly diminished baseline mean arterial blood pressure. These findings suggest cardiovascular effects of SPHK1 inhibition. |
| Enzyme Assay |
Not specifically documented for BML-258 HCl. For SPHK1 inhibitors, cell-free enzyme assays typically measure the inhibition of sphingosine phosphorylation using recombinant SPHK1 enzyme and radiolabeled ATP or fluorescent substrates. The Ki value of 10 µM for SPHK1 was determined through such competitive inhibition assays. Selectivity profiling against other kinases is performed using similar enzyme activity assays.
|
| Cell Assay |
Cell Viability Assay[2]
Cell Types: HCT116 cells and HCT116 cells with TP53 null cancer Tested Concentrations: 0 µM, 2.5 µM, 5 µM, 7.5 µM, 10 µM Incubation Duration: 24 hrs (hours) Experimental Results: diminished cancer cell growth and survival. Western Blot Analysis[2] Cell Types: HCT116 cells and HCT116 cells with TP53 null cancer Tested Concentrations: 0 µM, 5 µM, 10 µM, 20 µM Incubation Duration: 12 hrs (hours) Experimental Results: In HCT116 cells compared to HCT116 cells Induces greater CASP3 cleavage in the absence of TP53. In vitro cell-based assays for BML-258 HCl include cell viability and proliferation assays in cancer cell lines such as HCT116. Cells are treated with varying concentrations (0-10 µM) for 24 hours, and cell growth is assessed. Western blot analysis for CASP3 cleavage is performed after treatment with 0-20 µM for 12 hours to evaluate apoptosis induction. TP53-dependent effects are studied by comparing TP53-proficient and TP53-null cell lines. |
| Animal Protocol |
Animal/Disease Models: Male C57BL/6 mice (24 ± 3.5 g) [3]
Doses: 75 mg/kg Route of Administration: intraperitoneal (ip) injection; once; baseline MAP measurement 24 hrs (hrs (hours)) before Experimental Results: baseline mean arterial blood pressure ( MAP) was Dramatically diminished. In vivo animal studies with BML-258 HCl have been conducted in male C57BL/6 mice. Animals received the compound at 75 mg/kg via intraperitoneal injection. Baseline mean arterial blood pressure was measured 24 hours after administration. The compound significantly reduced baseline MAP. Additional studies may involve anandamide-induced hypotension models. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for BML-258 HCl are not extensively documented in the available literature. The compound is a small molecule with molecular weight 313.86 and formula C17H27NO2·HCl. It appears as an off-white to light yellow solid powder. The compound should be stored appropriately to maintain stability. Detailed PK parameters such as half-life and bioavailability have not been reported.
|
| Toxicity/Toxicokinetics |
Specific toxicity data for BML-258 HCl are not provided in the available sources. As a research compound, it is not intended for human use. Standard laboratory safety precautions should be followed when handling this compound. The product has been discontinued by some suppliers, which may limit availability for further toxicological evaluation.
|
| References |
|
| Additional Infomation |
BML-258 HCl is also known as SK1-I and (1E)-1,2,4-Trideoxy-4-(methylamino)-1-(4-pentylphenyl)-D-erythro-pent-1-enitol hydrochloride. The molecular weight is 313.86. The compound is soluble in DMSO and other organic solvents. It is supplied for research use only and is not for human therapeutic applications. Some suppliers have discontinued this product.
|
| Molecular Formula |
C17H27NO2.HCL
|
|---|---|
| Molecular Weight |
313.86272
|
| Exact Mass |
313.181
|
| CAS # |
1072443-89-0
|
| Related CAS # |
SK1-I hydrochloride;2366222-05-9
|
| PubChem CID |
44815217
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
3.566
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
20
|
| Complexity |
260
|
| Defined Atom Stereocenter Count |
2
|
| SMILES |
CCCCCC1=CC=C(C=C1)/C=C/[C@@H]([C@@H](CO)NC)O
|
| InChi Key |
JYEXUQKROPHSEF-SFDDJJRUSA-N
|
| InChi Code |
InChI=1S/C17H27NO2/c1-3-4-5-6-14-7-9-15(10-8-14)11-12-17(20)16(13-19)18-2/h7-12,16-20H,3-6,13H2,1-2H3/b12-11+/t16-,17+/m1/s1
|
| Chemical Name |
(E,2R,3S)-2-(methylamino)-5-(4-pentylphenyl)pent-4-ene-1,3-diol
|
| 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 (~360.49 mM)
|
|---|---|
| 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 | 3.1861 mL | 15.9307 mL | 31.8613 mL | |
| 5 mM | 0.6372 mL | 3.1861 mL | 6.3723 mL | |
| 10 mM | 0.3186 mL | 1.5931 mL | 3.1861 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
