15639-50-6 Usage
Uses
Different sources of media describe the Uses of 15639-50-6 differently. You can refer to the following data:
1. 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.
2. L-threo-Dihydrosphingosine is a lyso-sphingolipid protein kinase C inhibitor. It suppresses the growth of human oral squamous cell carcinoma (SCC) cells.
3. Safingol has been used as a substituent of dihydrosphingosine (dhSph) to increase the cytotoxic response in N-(4-hydroxyphenyl)retinamide (4-HPR)-resistant cells.
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 PKCα, 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
Check Digit Verification of cas no
The CAS Registry Mumber 15639-50-6 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,5,6,3 and 9 respectively; the second part has 2 digits, 5 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 15639-50:
(7*1)+(6*5)+(5*6)+(4*3)+(3*9)+(2*5)+(1*0)=116
116 % 10 = 6
So 15639-50-6 is a valid CAS Registry Number.
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
15639-50-6Relevant articles and documents
Convergent evolution of bacterial ceramide synthesis
Ashley, Ben,Campopiano, Dominic J.,Chamberlain, Joshua D.,Coleman, Aimiyah,D’Emilia, Rachel,Fu, Larina,Guan, Ziqiang,Hansen, Matthew E. B.,Klein, Eric A.,Mohan, Eric C.,Nguyen, Hung,Stankeviciute, Gabriele,Tang, Peijun
, (2022/01/06)
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])
Touge, Taichiro,Kuwana, Masahiro,Komatsuki, Yasuhiro,Tanaka, Shigeru,Nara, Hideki,Matsumura, Kazuhiko,Sayo, Noboru,Kashibuchi, Yoshinobu,Saito, Takao
supporting information, p. 452 - 461 (2019/01/04)
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
Das, Pintu,Kundooru, Somireddy,Shaw, Arun K.
, p. 14505 - 14511 (2016/02/19)
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.