Safingol
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MedKoo CAT#: 412715

CAS#: 15639-50-6

Description: Safingol is a lyso-sphingolipid protein kinase inhibitor. It has the molecular formula C₁₈H₃₉NO₂ and is a colorless solid. Medicinally, safingol has demonstrated promising anticancer potential as a modulator of multi-drug resistance and as an inducer of necrosis.


Chemical Structure

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Safingol
CAS# 15639-50-6

Theoretical Analysis

MedKoo Cat#: 412715
Name: Safingol
CAS#: 15639-50-6
Chemical Formula: C18H39NO2
Exact Mass: 301.30
Molecular Weight: 301.520
Elemental Analysis: C, 71.70; H, 13.04; N, 4.65; O, 10.61

Price and Availability

Size Price Availability Quantity
1mg USD 450 2 Weeks
5mg USD 750 2 weeks
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Synonym: Safingol; L-threo-dihydrosphingosine (d18:0) z

IUPAC/Chemical Name: (2S,3S)-2-aminooctadecane-1,3-diol

InChi Key: OTKJDMGTUTTYMP-ROUUACIJSA-N

InChi Code: InChI=1S/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

SMILES Code: CCCCCCCCCCCCCCC[C@@](O)([H])[C@@]([H])(N)CO

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in ethanol

Shelf Life: >3 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Product Data:
Biological target: Safingol inhibits PKC by binding at the regulatory phorbol-binding domain (IC50 = 24 µM). Safingol also inhibits SPHK (Ki = ~5 µM) and restores sensitivity to cisplatin in resistant AGScis5 cells and N87 gastric cancer cells.
In vitro activity: This study investigated the anti-cancer effect of safingol as a single agent or in combination with irinotecan. As a single agent, safingol was more potent than irinotecan and 5-FU, with IC50 values of 2.5+/-1.1 microM and 3.4+/-1.0 microM achieved in HT-29 and LS-174T colon cancer cells, respectively, but safingol did not inhibit PKC. Safingol/irinotecan combination was additive in HT-29 cells and synergistic in LS-174T cells. Reference: Int J Oncol. 2009 Dec;35(6):1463-71. https://pubmed.ncbi.nlm.nih.gov/19885570/
In vivo activity: A liposomal formulation of safingol demonstrated significant anti-leukemic potential in various human acute myeloid leukemia (AML) cell lines, patient samples, and a human xenograft model in SCID mice. This formulation extended the median survival time of mice inoculated with AML cells, showing enhanced therapeutic efficacy while minimizing hemolytic toxicity. Reference: J Control Release. 2012 Jun 10;160(2):290-8. https://pubmed.ncbi.nlm.nih.gov/22100388/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
Ethanol 0.3 0.83

Preparing Stock Solutions

The following data is based on the product molecular weight 301.52 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Ling LU, Lin H, Tan KB, Chiu GN. The role of protein kinase C in the synergistic interaction of safingol and irinotecan in colon cancer cells. Int J Oncol. 2009 Dec;35(6):1463-71. doi: 10.3892/ijo_00000465. PMID: 19885570. 2. Coward J, Ambrosini G, Musi E, Truman JP, Haimovitz-Friedman A, Allegood JC, Wang E, Merrill AH Jr, Schwartz GK. Safingol (L-threo-sphinganine) induces autophagy in solid tumor cells through inhibition of PKC and the PI3-kinase pathway. Autophagy. 2009 Feb;5(2):184-93. doi: 10.4161/auto.5.2.7361. Epub 2009 Feb 6. PMID: 19098447. 3. Tan KB, Ling LU, Bunte RM, Chng WJ, Chiu GN. In vivo efficacy of a novel liposomal formulation of safingol in the treatment of acute myeloid leukemia. J Control Release. 2012 Jun 10;160(2):290-8. doi: 10.1016/j.jconrel.2011.11.002. Epub 2011 Nov 10. PMID: 22100388.
In vitro protocol: 1. Ling LU, Lin H, Tan KB, Chiu GN. The role of protein kinase C in the synergistic interaction of safingol and irinotecan in colon cancer cells. Int J Oncol. 2009 Dec;35(6):1463-71. doi: 10.3892/ijo_00000465. PMID: 19885570. 2. Coward J, Ambrosini G, Musi E, Truman JP, Haimovitz-Friedman A, Allegood JC, Wang E, Merrill AH Jr, Schwartz GK. Safingol (L-threo-sphinganine) induces autophagy in solid tumor cells through inhibition of PKC and the PI3-kinase pathway. Autophagy. 2009 Feb;5(2):184-93. doi: 10.4161/auto.5.2.7361. Epub 2009 Feb 6. PMID: 19098447.
In vivo protocol: 1. Tan KB, Ling LU, Bunte RM, Chng WJ, Chiu GN. In vivo efficacy of a novel liposomal formulation of safingol in the treatment of acute myeloid leukemia. J Control Release. 2012 Jun 10;160(2):290-8. doi: 10.1016/j.jconrel.2011.11.002. Epub 2011 Nov 10. PMID: 22100388.

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1: Coward J, Ambrosini G, Musi E, Truman JP, Haimovitz-Friedman A, Allegood JC, Wang E, Merrill AH Jr, Schwartz GK. Safingol (L-threo-sphinganine) induces autophagy in solid tumor cells through inhibition of PKC and the PI3-kinase pathway. Autophagy. 2009 Feb;5(2):184-93. doi: 10.4161/auto.5.2.7361. Epub 2009 Feb 6. PMID: 19098447.

2: Hamada M, Wakabayashi K, Masui A, Iwai S, Imai T, Yura Y. Involvement of hydrogen peroxide in safingol-induced endonuclease G-mediated apoptosis of squamous cell carcinoma cells. Int J Mol Sci. 2014 Feb 17;15(2):2660-71. doi: 10.3390/ijms15022660. PMID: 24549171; PMCID: PMC3958874.

3: Morales PR, Dillehay DL, Moody SJ, Pallas DC, Pruett S, Allgood JC, Symolon H, Merrill AH Jr. Safingol toxicology after oral administration to TRAMP mice: demonstration of safingol uptake and metabolism by N-acylation and N-methylation. Drug Chem Toxicol. 2007;30(3):197-216. doi: 10.1080/01480540701375018. PMID: 17613006.

4: Cho HE, Maurer BJ, Reynolds CP, Kang MH. Hydrophilic interaction liquid chromatography-tandem mass spectrometric approach for simultaneous determination of safingol and D-erythro-sphinganine in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Apr 1;1112:16-23. doi: 10.1016/j.jchromb.2019.02.023. Epub 2019 Feb 22. PMID: 30836314; PMCID: PMC6428217.

5: Ling LU, Tan KB, Lin H, Chiu GN. The role of reactive oxygen species and autophagy in safingol-induced cell death. Cell Death Dis. 2011 Mar 10;2(3):e129. doi: 10.1038/cddis.2011.12. PMID: 21390063; PMCID: PMC3101809.

6: Schwartz GK, Ward D, Saltz L, Casper ES, Spiess T, Mullen E, Woodworth J, Venuti R, Zervos P, Storniolo AM, Kelsen DP. A pilot clinical/pharmacological study of the protein kinase C-specific inhibitor safingol alone and in combination with doxorubicin. Clin Cancer Res. 1997 Apr;3(4):537-43. PMID: 9815717.

7: Dragusin M, Gurgui C, Schwarzmann G, Hoernschemeyer J, van Echten-Deckert G. Metabolism of the unnatural anticancer lipid safingol, L-threo- dihydrosphingosine, in cultured cells. J Lipid Res. 2003 Sep;44(9):1772-9. doi: 10.1194/jlr.M300160-JLR200. Epub 2003 Jun 1. PMID: 12777464.

8: Kelly R. Expression of concern: A general and concise asymmetric synthesis of sphingosine, safingol and phytosphingosines via tethered aminohydroxylation. Org Biomol Chem. 2017 Jul 21;15(27):5851. doi: 10.1039/c7ob90105d. Epub 2017 Jun 29. PMID: 28661539.

9: Tan KB, Ling LU, Bunte RM, Chng WJ, Chiu GN. In vivo efficacy of a novel liposomal formulation of safingol in the treatment of acute myeloid leukemia. J Control Release. 2012 Jun 10;160(2):290-8. doi: 10.1016/j.jconrel.2011.11.002. Epub 2011 Nov 10. PMID: 22100388.

10: Gantner ML, Eade K, Wallace M, Handzlik MK, Fallon R, Trombley J, Bonelli R, Giles S, Harkins-Perry S, Heeren TFC, Sauer L, Ideguchi Y, Baldini M, Scheppke L, Dorrell MI, Kitano M, Hart BJ, Cai C, Nagasaki T, Badur MG, Okada M, Woods SM, Egan C, Gillies M, Guymer R, Eichler F, Bahlo M, Fruttiger M, Allikmets R, Bernstein PS, Metallo CM, Friedlander M. Serine and Lipid Metabolism in Macular Disease and Peripheral Neuropathy. N Engl J Med. 2019 Oct 10;381(15):1422-1433. doi: 10.1056/NEJMoa1815111. Epub 2019 Sep 11. PMID: 31509666; PMCID: PMC7685488.