L-THREO-DIHYDROSPHINGOSINE Property

Melting point:

126-128 °C

Boiling point:

446.2±25.0 °C(Predicted)

Density 

0.927±0.06 g/cm3(Predicted)

Flash point:

110 °C

storage temp. 

-20°C

solubility 

≤0.25mg/ml in ethanol

form 

White solid

pka

12.57±0.45(Predicted)

Safety

WGK Germany 

3

Hazard and Precautionary Statements (GHS)

L-THREO-DIHYDROSPHINGOSINE Chemical Properties,Usage,Production

Uses

Safingol is the L-threo diastereomer of D-erythro-sphinganine Both forms of sphinganine inhibit PKC by binding at the regulatory phorbol-binding domain (IC50s = 7 and 24 μM for erythro-sphinganine and safingol, respectively). Safingol also inhibits sphingosine kinases (Ki = 3-5 μM). Safingol, alone or in combination with chemotherapeutic agents, is cytotoxic against cancer cell lines.

Uses

L-threo-Dihydrosphingosine is a lyso-sphingolipid protein kinase C inhibitor. It suppresses the growth of human oral squamous cell carcinoma (SCC) cells.

Uses

Safingol has been used as a substituent of dihydrosphingosine (dhSph) to increase the cytotoxic response in N-(4-hydroxyphenyl)retinamide (4-HPR)-resistant cells.

Definition

ChEBI: Safingol ( L-threo-sphinganine) is an amino alcohol.

General Description

A cell-permeable and reversible lyso-sphingolipid protein kinase C (PKC) inhibitor that competitively interacts at the regulatory phorbol binding domain of PKC. Inhibits enzymatic activity and ³H-phorbol dibutyrate binding of purified rat brain PKC (IC₅₀ = 37.5 μM and 31 μM, respectively). Inhibits human PKC_α, the major overexpressed isoenzyme in MCF-7 DOXR cells (IC₅₀ = 40 μM). Enhances the cytotoxic effect of the chemotherapeutic agent Mitomycin C (MMC; Cat. Nos. 47589 and 475820) in gastric cancer cells by promoting drug-induced apoptosis.

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