15639-50-6

Basic information

• Product Name: L-THREO-DIHYDROSPHINGOSINE
• Synonyms: SAFINGOL;L-THREO-SPHINGANINE, C18 CHAIN;L-THREO-DIHYDROSPHINGOSINE;L-threo-dihydrospingosine;L-threo-dihydrosphingosine (d18:0)
• CAS NO: 15639-50-6
• Molecular Formula: C₁₈H₃₉NO₂
• Molecular Weight: 301.51
• EINECS: 212-116-0
• Mol File: 15639-50-6.mol
• Article Data: 47

Chemical Properties

• Melting Point: 126-128 °C
• Boiling Point: 446.2 °C at 760 mmHg
• Flash Point: 110 °C
• Appearance: /
• Density: 0.927 g/cm³
• Vapor Pressure: 7.75E-10mmHg at 25°C
• Refractive Index: 1.477
• Storage Temp.: −20°C
• Solubility: ≤0.25mg/ml in ethanol
• PKA: 12.57±0.45(Predicted)
• CAS DataBase Reference: L-THREO-DIHYDROSPHINGOSINE(CAS DataBase Reference)
• NIST Chemistry Reference: L-THREO-DIHYDROSPHINGOSINE(15639-50-6)
• EPA Substance Registry System: L-THREO-DIHYDROSPHINGOSINE(15639-50-6)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 15639-50-6(Hazardous Substances Data)

Usage

Description

L-THREO-DIHYDROSPHINGOSINE, also known as Safingol, is a cell-permeable and reversible lyso-sphingolipid protein kinase C (PKC) inhibitor. It competitively interacts at the regulatory phorbol binding domain of PKC, inhibiting its enzymatic activity and 3H-phorbol dibutyrate binding. L-THREO-DIHYDROSPHINGOSINE has been found to suppress the growth of various cancer cell lines and enhance the cytotoxic effects of chemotherapeutic agents.

Uses

Used in Anticancer Applications:
L-THREO-DIHYDROSPHINGOSINE is used as a cytotoxic agent for inhibiting the growth of human oral squamous cell carcinoma (SCC) cells. It is also used in combination with chemotherapeutic agents to enhance their cytotoxic response in cancer cell lines, such as N-(4-hydroxyphenyl)retinamide (4-HPR)-resistant cells.
Used in Drug Delivery Systems:
L-THREO-DIHYDROSPHINGOSINE is used as a substituent of dihydrosphingosine (dhSph) to increase the cytotoxic response in drug-resistant cells, improving the effectiveness of cancer treatments.
Used in Enhancing Chemotherapy Efficacy:
L-THREO-DIHYDROSPHINGOSINE is used as an enhancer for promoting drug-induced apoptosis in gastric cancer cells when used in combination with the chemotherapeutic agent Mitomycin C (MMC).
Used in Pharmaceutical Research:
L-THREO-DIHYDROSPHINGOSINE is used as a research tool for studying the role of PKC in various cellular processes and its potential as a therapeutic target for cancer treatment.
Used in Cancer Cell Line Studies:
L-THREO-DIHYDROSPHINGOSINE is used as an inhibitor in the study of PKC's role in cancer cell growth and the development of resistance to chemotherapeutic agents.

Biological Activity

ki: sphk with a ki of about 5 μmol/lsafingol is a sphingosine and pkc kinases inhibitor.sphingosine 1-phosphate, a product of sphingosine kinases (sphk), mediates various biological processes including cell proliferation, differentiation, motility, and apoptosis. protein kinase c (pkc), is a family of protein kinase enzymes involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and threonine amino acid residues.

Biochem/physiol Actions

Sphingosine kinase inhibitor; protein kinase C alpha (PKCα) -specific inhibitor; Sphingosine analog; potentiates the effect of doxorubicin (DOX) in tumor-bearing animals.

in vitro

safingol was identified as a potent competitive inhibitor of sphk and had significant in-vitro anticancer activity. safingol could increase the in-vitro antitumor effect of various chemotherapeutic agents including cisplatin, doxorubicin, and mitomycin c via enhancing chemotherapy induced apoptosis. it was also found that safingol alone induced cell death by autophagy. safingol was also extensively studied as an inhibitor of pkc, although the ki was higher than that for sphk [1].

in vivo

previous studies found that although safingol showed limited single-agent activity in vivo, xenograft experiments had indicated that safingol could increase the antitumor activity of cisplatin without increasing toxicity [1].

references

[1] dickson ma, carvajal rd, merrill ah jr, gonen m, cane lm, schwartz gk. a phase i

InChI:InChI=1/C18H39NO2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-18(21)17(19)16-20/h17-18,20-21H,2-16,19H2,1H3/t17-,18-/m0/s1

Upstream product

• 3102-56-5 dihydrosphingosine 
• 123-78-4 (2S,3R,4E)-2-amino-4-octadecene-1,3-diol 
• 25834-63-3 N-Benzyloxycarbonyl-D-erythro-sphingosin 
• 14663-15-1 (+/-)-erythro-2-benzylamino-octadecane-1,3-diol 
• 76334-09-3 D-erythro-1-β-D-galactopyranosyloximethyl-2-tetracosanoylamino-octadecan-3-ol 
• 13031-64-6 (2S,3R)-2-acetylaminooctadecan-1,3-diol 
• 81306-31-2 (2R,3R)-2,3-epoxyoctadecan-1-ol 
• 140408-14-6 (2S,3R)-N-(tert-butoxycarbonyl)-<2-amino-1,3-dihydroxyoctadecane> 
• 75355-78-1 (2S,3R)-erythro-2-phthalimidooctadecane-1,3-diol 
• 3173-56-6 benzyl isothiocyanate 
• 98048-64-7 (2S,3R)-2-benzylamino-1,3-octadecanediol 
• 97975-08-1 1-<(N-benzylcarbamoyl)oxy>-trans-2,3-epoxyoctadecane 
• 158021-50-2 (2S,3R)-2-azido-1,3-octadecanediol 
• 105617-34-3 (2S,3R)-2-amino-1,3-dihydroxyoctadec-4-yne 

Downstream Products

• 34227-83-3 dihydroceramide d18:0/18:1(9Z) 
• 197302-96-8 N-((1S,2R)-2-hydroxy-1-hydroxymethyl-heptadecyl)-lauramide 
• 629-80-1 n-hexadecylaldehyde 
• 1002-84-2 palmitic acid 
• 57-10-3 1-hexadecylcarboxylic acid 
• 6036-86-8 (-)-L-threo-sphinganine 
• 21481-56-1 (2S,3R)-2-octadecanoylaminooctadecane-1,3-diol 
• 21275-74-1 dihydroceramide 
• 103044-89-9 (2S,3R)-2-benzylideneamino-octadecane-1,3-diol 
• 13031-64-6 (2S,3R)-2-acetylaminooctadecan-1,3-diol 
• 50-00-0 formaldehyd 
• 64-18-6 formic acid 
• 7664-41-7 ammonia 
• 2304-76-9 erythro-(2S,3S)-N,O,O-tribenzoyl-dihydrosphingosine 

Relevant articles and documents

Convergent evolution of bacterial ceramide synthesis

The bacterial domain produces numerous types of sphingolipids with various physiological functions. In the human microbiome, commensal and pathogenic bacteria use these lipids to modulate the host inflammatory system. Despite their growing importance, their biosynthetic pathway remains undefined since several key eukaryotic ceramide synthesis enzymes have no bacterial homolog. Here we used genomic and biochemical approaches to identify six proteins comprising the complete pathway for bacterial ceramide synthesis. Bioinformatic analyses revealed the widespread potential for bacterial ceramide synthesis leading to our discovery of a Gram-positive species that produces ceramides. Biochemical evidence demonstrated that the bacterial pathway operates in a different order from that in eukaryotes. Furthermore, phylogenetic analyses support the hypothesis that the bacterial and eukaryotic ceramide pathways evolved independently. [Figure not available: see fulltext.]

Development of Asymmetric Transfer Hydrogenation with a Bifunctional Oxo-Tethered Ruthenium Catalyst in Flow for the Synthesis of a Ceramide (D-erythro-CER[NDS])

The development of an efficient synthetic route for an optically active ceramide compound (d-erythro-CER[NDS]) is described. The route proceeds through asymmetric transfer hydrogenation in a pipes-in-series flow reactor with oxo-tethered ruthenium complex-catalyzed dynamic kinetic resolution. This synthesis was accomplished without any expensive reagents, and none of the intermediates required isolation. This resulted in a robust process that has been successfully run on a production scale.

'Chiron' approach to stereoselective synthesis of sphinganine and unnatural safingol, an antineoplastic and antipsoriatic agent

Highly stereoselective total syntheses of sphingoid bases, natural bioactive ceramide sphinganine 1 (with an overall yield of 33%) and unnatural antineoplastic and antipsoriatic drug safingol 17 (with an overall yield of 38%) starting from chirons 3,4,6-tri-O-benzyl-d-galactal and 3,4,6-tri-O-benzyl-d-glucal respectively have been demonstrated. Mitsunobu reaction and late stage olefin cross metathesis are utilized as important steps in order to complete the total synthesis of these sphingoid molecules.