SAFINGOL

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H39NO2
Molecular Weight	301.5078
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCCCCCCCCCCCCC[C@H](O)[C@@H](N)CO

InChI

InChIKey=OTKJDMGTUTTYMP-ROUUACIJSA-N

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

HIDE SMILES / InChI

Molecular Formula	C18H39NO2
Molecular Weight	301.5078
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19098447 | https://www.ncbi.nlm.nih.gov/pubmed/22866148 | https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=41910 | https://www.ncbi.nlm.nih.gov/pubmed/7665004 | https://www.ncbi.nlm.nih.gov/pubmed/7592889

Safingol, the synthetic L-threo-stereoisomer of endogenous (D-erythro-) sphinganine, is an inhibitor of protein kinase C and sphingosine kinase in vitro, and in some cell types has been implicated in ceramide generation and induction of apoptosis. Safingol inhibits enzymatic activity and 3H-phorbol dibutyrate binding of purified rat brain PKC (IC50 = 37.5 uM and 31uM, respectively). Inhibits human PKCα, the major overexpressed isoenzyme in MCF-7 DOXR cells (IC50 = 40 uM). Safingol enhances the cytotoxic effect of the chemotherapeutic agent Mitomycin C (MMC) in gastric cancer cells by promoting drug-induced apoptosis. Safingol is an inhibitor of SphK (Sphingosine kinase). Safingol has been shown to act synergistically with other chemotherapeutic agents and may potentiate chemotherapy drug-induced apoptosis in vitro and in vivo.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Sphingosine kinase 1 6 Target ID: CHEMBL4394 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24471412	Inhibitor 8504	3.0 µM [Ki]
Protein kinase C beta 22 Target ID: CHEMBL3045 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19098447 \| https://www.ncbi.nlm.nih.gov/pubmed/9547581	Inhibitor 8504
Protein kinase C delta 11 Target ID: CHEMBL2996 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19098447	Inhibitor 8504
Protein kinase C epsilon 5 Target ID: CHEMBL3582 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19098447	Inhibitor 8504
Protein kinase C alpha 21 Target ID: CHEMBL299 Sources: https://www.scbt.com/scbt/product/safingol-15639-50-6	Inhibitor 8504	40.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 609 Sources: https://clinicaltrials.gov/ct2/show/NCT01553071	Primary		Phase I 438	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
25.6 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21257722	930 mg/m² single, intravenous dose: 930 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: CISPLATIN	CISPLATIN	SAFINGOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
23.5 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21257722	840 mg/m² 1 times / 3 weeks single, intravenous dose: 840 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: CISPLATIN	CISPLATIN	SAFINGOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1040 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9815717	120 mg/m² single, intravenous dose: 120 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		SAFINGOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
104.9 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21257722	930 mg/m² single, intravenous dose: 930 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: CISPLATIN	CISPLATIN	SAFINGOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
109.9 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21257722	840 mg/m² 1 times / 3 weeks single, intravenous dose: 840 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered: CISPLATIN	CISPLATIN	SAFINGOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1251 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9815717	120 mg/m² single, intravenous dose: 120 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		SAFINGOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
3.97 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9815717	120 mg/m² single, intravenous dose: 120 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		SAFINGOL plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
930 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose Dose: 930 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 930 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/21257722	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21257722	DLT: Increased AST, ALT increased... Dose limiting toxicities: Increased AST (grade 3-4, 33.3%) ALT increased (grade 3-4, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/21257722
840 mg/m2 1 times / 3 weeks multiple, intravenous MTD Dose: 840 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 840 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/21257722	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21257722	DLT: AST increased, ALT increased... Dose limiting toxicities: AST increased (grade 3, 16.7%) ALT increased (grade 3, 16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/21257722

AEs

AE	Significance	Dose	Population
ALT increased	grade 3-4, 33.3% DLT	930 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose Dose: 930 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 930 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/21257722	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21257722
Increased AST	grade 3-4, 33.3% DLT	930 mg/m2 1 times / 3 weeks multiple, intravenous Highest studied dose Dose: 930 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 930 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/21257722	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21257722
ALT increased	grade 3, 16.7% DLT	840 mg/m2 1 times / 3 weeks multiple, intravenous MTD Dose: 840 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 840 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/21257722	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21257722
AST increased	grade 3, 16.7% DLT	840 mg/m2 1 times / 3 weeks multiple, intravenous MTD Dose: 840 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 840 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/21257722	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/21257722

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P001P6H	https://www.1pchem.com/search?query=1P001P6H
1PlusChem LLC	1P00BD06	https://www.1pchem.com/search?query=1P00BD06
AK Scientific	X6879	https://aksci.com/item_detail.php?cat=X6879
Alfa Chemistry	74834	http://www.alfa-chemistry.com/search.aspx?q=74834
Alfa Chemistry	ACM15639506	http://www.alfa-chemistry.com/search.aspx?q=ACM15639506
ApexBio Technology	B6434	https://www.apexbt.com/catalogsearch/result/?q=B6434
ApexBio Technology	C3243	https://www.apexbt.com/catalogsearch/result/?q=C3243
BioSynth	A-6850	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/A-6850
BioSynth	D-3620	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/D-3620
BOC Sciences	13552-09-5	http://www.bocsci.com/description.asp?cas=13552-09-5
BOC Sciences	764-22-7	http://www.bocsci.com/description.asp?cas=764-22-7
Cayman Chemical	10007945	http://www.caymanchem.com/app/template/Product.vm/catalog/10007945
Cayman Chemical	18624	http://www.caymanchem.com/app/template/Product.vm/catalog/18624
eMolecules	206928056	https://orderbb.emolecules.com/search/#?query=206928056
eMolecules	537553	https://orderbb.emolecules.com/search/#?query=537553
Hairui	HR139905	http://www.hairuichem.com/en/product/search.do?q=HR139905
Indofine	56-1306	https://indofinechemical.com/details.aspx?Sku=56-1306
MolPort	MolPort-003-941-131	https://www.molport.com/shop/molecule-link/MolPort-003-941-131
MuseChem	R020718	https://www.musechem.com/product/R020718.html
Sigma Aldrich	860488P	http://www.sigmaaldrich.com/catalog/search?term=860488P&interface=All&N=0&mode=match%20partialmax&lang=en®ion=US&focus=product
Tetrahedron	TS59092	http://www.thsci.com/search.do?q=TS59092
Toronto Research Chemicals	D689955	https://www.trc-canada.com/product-detail/?CatNum=D689955
Toronto Research Chemicals	G299920	https://www.trc-canada.com/product-detail/?CatNum=G299920
Vesino Industrial Co Ltd	VZ31872	http://www.vsnchem.com/search.do?a=s&psize=20&q=VZ31872

PubMed

Title	Date	PubMed
Mechanisms of sphingosine and sphingosine 1-phosphate generation in human platelets.	2005-11	16061940
Inhibition of tumor necrosis factor alpha signaling by anti-tumor necrosis factor alpha antibodies and pentoxifylline is unable to prevent fumonisin hepatotoxicity in mice.	2005-09-15	16054185
Ceramides, sphinganine, sphingosine and acid sphingomyelinases in the human umbilical cord blood.	2005-07	16034716
Maternal fumonisin exposure and risk for neural tube defects: mechanisms in an in vivo mouse model.	2005-07	15959874
Effects of exogenous sphinganine, sphingosine, and sphingosine-1-phosphate on relaxation and contraction of porcine thoracic aortic and pulmonary arterial rings.	2005-07	15829618
Survival role of protein kinase C (PKC) in chronic lymphocytic leukemia and determination of isoform expression pattern and genes altered by PKC inhibition.	2005-06	15929099
Myriocin prevents fumonisin B1-induced sphingoid base accumulation in mice liver without ameliorating hepatotoxicity.	2005-06	15811577
Chronic effects of fumonisin B1 on ducks.	2005-01	15685938
Concentrations of sphingosine and sphinganine in plasma of patients with type 2 diabetes.	2005-01	15614193
The luteinizing hormone-releasing hormone inhibits the anti-apoptotic activity of insulin-like growth factor-1 in pituitary alphaT3 cells by protein kinase Calpha-mediated negative regulation of Akt.	2004-12-10	15448167
Inhibition of sphingomyelin synthesis reduces atherogenesis in apolipoprotein E-knockout mice.	2004-11-30	15545514
Protein kinase C alpha/beta inhibitor Go6976 promotes formation of cell junctions and inhibits invasion of urinary bladder carcinoma cells.	2004-08-15	15313909
Fenretinide cytotoxicity for Ewing's sarcoma and primitive neuroectodermal tumor cell lines is decreased by hypoxia and synergistically enhanced by ceramide modulators.	2004-08-01	15289350
Toxicity of maize containing known levels of fumonisin B1 during force-feeding of ducks.	2004-08	15339002
The immune modulator FTY720 targets sphingosine-kinase-dependent migration of human monocytes in response to amyloid beta-protein and its precursor.	2004-08	15208267
Disruption of sphingolipid biosynthesis in hepatocyte nodules: selective proliferative stimulus induced by fumonisin B1.	2004-07-15	15158565
Ceramide metabolite, not intact ceramide molecule, may be responsible for cellular toxicity.	2004-06-15	14998372
DES2 protein is responsible for phytoceramide biosynthesis in the mouse small intestine.	2004-05-01	14731113
Intrinsic cytotoxicity and chemomodulatory actions of novel phenethylisothiocyanate sphingoid base derivatives in HL-60 human promyelocytic leukemia cells.	2004-05	14724218
Straightforward synthesis of sphinganines via a serine-derived Weinreb amide.	2004-04-30	15104474
Cloning and functional characterization of the SUR2/SYR2 gene encoding sphinganine hydroxylase in Pichia ciferrii.	2004-04-15	15116344
Inhibition of serine palmitoyltransferase by myriocin, a natural mycotoxin, causes induction of c-myc in mouse liver.	2004-04	15180163
Sphingolipids as bioactive regulators of thrombin generation.	2004-03-26	14722105
Clostridium perfringens alpha-toxin activates the sphingomyelin metabolism system in sheep erythrocytes.	2004-03-26	14702348
Myriocin, a serine palmitoyltransferase inhibitor, alters regional brain neurotransmitter levels without concurrent inhibition of the brain sphingolipid biosynthesis in mice.	2004-02-28	14700532
Cycloserine and threo-dihydrosphingosine inhibit TNF-alpha-induced cytotoxicity: evidence for the importance of de novo ceramide synthesis in TNF-alpha signaling.	2003-12-07	14654222
Quantification of sphingosine and sphinganine from crude lipid extracts by HPLC electrospray ionization tandem mass spectrometry.	2003-11	12897185
Induction of apoptosis in cultured human proximal tubule cells by fumonisins and fumonisin metabolites.	2003-10-15	14550748
Efficient synthesis of enantiomerically pure 2-acylaziridines: Facile syntheses of N-Boc-safingol, N-Boc-D-erythro-sphinganine, and N-Boc-spisulosine from a common intermediate.	2003-10-03	14510541
Metabolism of the unnatural anticancer lipid safingol, L-threo-dihydrosphingosine, in cultured cells.	2003-09	12777464
Sphinganine to sphingosine ratio and predictive biochemical markers of fumonisin B1 exposure in ducks.	2003-07-25	12902153
Synthesis of 4-hydroxysphinganine and characterization of sphinganine hydroxylase activity in corn.	2003-07-15	12831841
Metabolomic profiling of sphingolipids in human glioma cell lines by liquid chromatography tandem mass spectrometry.	2003-07	14528916
Protein kinase C-delta is commonly expressed in multiple myeloma cells and its downregulation by rottlerin causes apoptosis.	2003-06	12786795
Using lowess to remove systematic trends over time in predictor variables prior to logistic regression with quantile categories.	2003-05-15	12704611
Selective roles of protein kinase C isoforms on cell motility of GT1 immortalized hypothalamic neurones.	2003-05	12694376
[The changes in the sphingenine/sphinganine ratio in sphingolipids of transplantable rat tumors depends on a transplantation organ].	2003-04-24	12708324
Antinutritional effects of fumonisin B1 and pathophysiological consequences.	2003-04-11	12676494
Sphingoid bases as possible diagnostic parameters.	2003-04	12698507
A protein kinase Cbeta inhibitor attenuates multidrug resistance of neuroblastoma cells.	2003-03-26	12697075
A novel role for sphingolipid intermediates in activation-induced cell death in T cells.	2003-02	12700647
Deletion of IFN-gamma reduces fumonisin-induced hepatotoxicity in mice via alterations in inflammatory cytokines and apoptotic factors.	2003-01	12639295
Modulators of ceramide metabolism sensitize colorectal cancer cells to chemotherapy: a novel treatment strategy.	2003-01	12559195
Protein kinase C-alpha activation by phorbol ester induces secretion of gelatinase B/MMP-9 through ERK 1/2 pathway in capillary endothelial cells.	2003-01	12469196
Fumonisins and fumonisin analogs as inhibitors of ceramide synthase and inducers of apoptosis.	2002-12-30	12531553
Comparison of the toxicity of several fumonisin derivatives in a 28-day feeding study with female B6C3F(1) mice.	2002-12-15	12498732
Prolonged activation of Ca2+-activated K+ current contributes to the long-lasting refractory period of Aplysia bag cell neurons.	2002-12-01	12451114
Participation of protein kinase C alpha isoform and extracellular signal-regulated kinase in neurite outgrowth of GT1 hypothalamic neurons.	2002-12	12472895
Comparative study of naphthalene-2,3-dicarboxaldehyde and o-phthalaldehyde fluorogenic reagents for chromatographic detection of sphingoid bases.	2002-11-15	12456096
[Survey on the fumonisins intake and the urinary Sa/So ratio of people suffered from a high incidence of esophageal cancer].	2001-11	12561623

Patents

Sample Use Guides

In Vivo Use Guide

Solid Tumor treatment: Drug: Fenretinide (4-HPR) plus Intravenous Safingol A course for this study is defined as the 5 days of treatment with Fenretinide (4-HPR) plus Safingol followed by 16 days of rest. A course is repeated every 21 days if there is no clinical evidence of disease progression for a maximum of six 5-day infusions. Days 1-5 of every cycle: Day 1 Fenretinide (4-HPR) intravenous emulsion: 600 mg/m2 for 24 hours Given concurrently (at the same time) with: Safingol intravenous 210 mg/m2 for 24 hours Day 2 Fenretinide (4-HPR) intravenous emulsion: 1000 mg/m2 for 24 hours Given concurrently (at the same time) with: Safingol intravenous 210 mg/m2 for 24 hours Days 3-5 Fenretinide (4-HPR) intravenous emulsion: 1000 mg/m2 continuously for 3 days Days 8 and 15.

Route of Administration: Intravenous

In Vitro Use Guide

Safingol was most potent in SKOV-3, an ovarian cancer cell line, with an IC50 of 1.4±0.18 uM. The IC50 values of safingol in breast, ovarian, leukemic and nasopharynx cancer cell lines are within the same order of magnitude, ranging from 1.4-6.3 uM.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:06:28 GMT 2025` Edited by `admin` on `Mon Mar 31 18:06:28 GMT 2025`
Record UNII	OWA98U788S
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

NSC-714503

Preferred Name

English

SAFINGOL

Official Name

English

safingol [INN]

Common Name

English

(2S,3S)-2-Amino-1,3-octadecanediol

Systematic Name

English

SAFINGOL [USAN]

Common Name

English

SPC-100270

Code

English

1,3-OCTADECANEDIOL, 2-AMINO-, (S-(R*,R*))-

Common Name

English

THREO-DIHYDROSPHINGOSINE,L-

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2089