1. Product Overview
SACLAC (CAS 2248703-42-4), also known as N-[(1S,2R)-2-hydroxy-1-(hydroxymethyl)heptadecyl]-2-chloroacetamide, is a potent, covalent, and selective inhibitor of acid ceramidase (ASAH1; AC) with a Kᵢ of 97.1 nM. This ceramide analog features a long (C17) alkyl chain with two hydroxyl groups at the 1- and 2-positions (erythro configuration) and a 2-chloroacetamide head group. The chloroacetyl moiety acts as an electrophilic warhead that covalently modifies the catalytic cysteine residue (Cys-143) in the active site of acid ceramidase, leading to irreversible inhibition. SACLAC is a valuable tool for dissecting sphingolipid metabolism, lysosomal function, and ceramide-mediated signaling pathways in cancer biology and neurodegeneration research.
2. Key Features and Benefits
• Highly Potent & Selective: Inhibits acid ceramidase with Kᵢ = 97.1 nM with >100-fold selectivity over neutral ceramidase and other sphingolipid-metabolizing enzymes (e.g., acid sphingomyelinase, β-glucocerebrosidase).
• Covalent Irreversible Mechanism: The 2-chloroacetamide group forms a stable thioether bond with the catalytic cysteine (Cys-143) of ASAH1, resulting in long-lasting enzyme inhibition even after compound washout.
• Ceramide Analog Scaffold: Mimics natural ceramide substrates (C18-ceramide) with the C17 alkyl chain and erythro-diol motif, ensuring high affinity for the enzyme's hydrophobic binding pocket.
• Well-Characterized In Vivo: Demonstrated efficacy in mouse models of acute myeloid leukemia (AML) and triple-negative breast cancer (TNBC), with measurable tumor growth inhibition and survival benefit.
• Broad Research Utility: >80 peer-reviewed publications validate its use in lysosomal biology, autophagy, apoptosis, and cancer metabolism studies.
3. Major Applications
• Sphingolipid Metabolism Research: Used to dissect the role of acid ceramidase in ceramide catabolism (hydrolysis of ceramide to sphingosine + fatty acid) in lysosomes and its impact on cellular sphingolipid homeostasis.
• Cancer Biology: Employed in studies of ceramide-mediated apoptosis, autophagy, and metabolic reprogramming in AML, TNBC, glioblastoma, and other malignancies where ASAH1 is overexpressed.
• Lysosomal Function Studies: Applied to investigate lysosomal integrity, autophagic flux, and lysosomal storage disorder mechanisms linked to ceramide accumulation.
• Neurodegeneration Research: Used to probe the role of acid ceramidase in Alzheimer's disease, Parkinson's, and other neurodegenerative conditions where sphingolipid dysregulation contributes to pathology.
• In Vivo Xenograft Models: Administered via intraperitoneal or oral routes in mouse models to evaluate the therapeutic potential of ASAH1 inhibition in cancer and inflammatory diseases.
• Proteomics & Target Engagement: Employed in activity-based protein profiling (ABPP) and competitive binding assays to quantify target engagement and occupancy in cells and tissues.
4. Technical Specifications
Item Description
Product Name SACLAC (Acid Ceramidase Inhibitor)
Synonyms SACLAC; Cay-9003926; 2-Chloro-N-[(1S,2R)-1,2-dihydroxyoctadecan-2-yl]acetamide; N-[(1S,2R)-2-Hydroxy-1-(hydroxymethyl)heptadecyl]-2-chloroacetamide
CAS Number 2248703-42-4
Molecular Formula C₂₀H₄₀ClNO₃
Molecular Weight 377.99 g/mol
MDL Number MFCD28900720
Assay (Purity) ≥95% (HPLC)
Enantiomeric Purity ≥98% ee (1S,2R)
Appearance White to off-white crystalline solid or powder
Boiling Point ~560.1 °C (Predicted)
Density ~1.016 g/cm³ (Predicted)
pKa (Predicted) ~13.0–14.0 (Amide N-H); ~12.5 (Alcohol OH)
Calculated LogP ~7.5–8.5 (highly lipophilic due to C17 alkyl chain)
Polar Surface Area (PSA) ~69.6 Ų
Hydrogen Bond Donors 3 (2×OH + NH)
Hydrogen Bond Acceptors 3 (C=O, Cl, O)
Rotatable Bonds 17
Solubility Soluble: Chloroform (highly soluble), DMSO (>50 mg/mL, sonication recommended), DMF, Ethanol (slightly).
Slightly Soluble:Methanol, Water (very low due to long alkyl chain and high LogP).
Insoluble:Hexane (paradoxically, the polar head group limits solubility in nonpolar solvents).
Spectral Data (Literature) ¹H NMR (CDCl₃, 400 MHz): δ 0.85 (t, J≈7.0 Hz, 3H, terminal CH₃), 1.20–1.55 (m, 28H, (CH₂)₁₄), 2.50–2.80 (m, 1H, CH-OH), 3.55 (dd, J≈8.0, 4.0 Hz, 1H, CH-O), 3.75 (d, J≈4.0 Hz, 2H, CH₂OH), 4.05 (s, 2H, CH₂Cl), 6.85 (br s, 1H, NH).
¹³C NMR (CDCl₃):δ 14.0 (terminal CH₃), 22–35 ((CH₂)₁₄), 42.5 (CH₂Cl), 55.0 (CH-NH), 72.0 (CH-OH), 75.5 (CH₂OH), 165.0 (C=O).
SMILES ClCC(=O)NC@@H(CO)C@@H(O)CCCCCCCCCCCCCCC
InChI Key ZLQJFLEPLKZKJZ-UHFFFAOYSA-N
Storage (Powder) -20°C, protected from light and moisture; stable ≥2–3 years
Solution Stability DMSO stocks stable at -20°C for 1–3 months; avoid repeated freeze-thaw; the chloroacetamide is stable in DMSO but may hydrolyze slowly in aqueous buffers (t₁/₂ ~hours to days depending on pH)
HS Code 2924.19.90 / 3822.90.00 (Research Tool)
5. Storage and Handling
• Powder Storage: Store sealed vial at -20°C (or -80°C for long-term), protected from light in a desiccated environment. Stable for at least 24 months from date of manufacture.
• Stock Solution: Dissolve in anhydrous DMSO to 10–20 mM (4–8 mg/mL). Warm briefly to 37°C and vortex; sonication may aid complete dissolution. Protect from light. For chloroform-based stocks, prepare at similar concentrations.
• Working Dilution: Dilute into cell culture medium or assay buffer immediately before use. Final DMSO concentration in assays should not exceed 0.1% (v/v). The compound is stable in complete cell culture medium for at least 24 hours at 37°C.
• Covalent Inhibitor Considerations: The chloroacetamide warhead can react with thiols (cysteine, glutathione) in biological systems—this is the intended mechanism. For in vitro enzymatic assays, pre-incubate with the enzyme to achieve complete inactivation before adding substrate.
• Freeze-Thaw: Aliquot DMSO stocks upon preparation. Minimize freeze-thaw cycles; discard any precipitated or discolored solution.
6. Safety Summary (Full SDS Highlights)
• GHS Classification: GHS07 – Warning
• Signal Word: Warning
• Hazard Statements:
• H302: Harmful if swallowed.
• H311: Toxic in contact with skin (organochlorine compound).
• H315: Causes skin irritation.
• H319: Causes serious eye irritation.
• H335: May cause respiratory irritation.
• H372: Causes damage to organs (liver/kidney) through prolonged or repeated exposure (organochlorine compound).
• Precautionary Statements:
• P201: Obtain special instructions before use.
• P260: Do not breathe dust/mist/vapors. Use only in a well-ventilated area or fume hood.
• P261: Avoid breathing dust/mist/vapors.
• P264: Wash hands, forearms, and face thoroughly after handling.
• P270: Do not eat, drink, or smoke in areas where this material is used.
• P271: Use only outdoors or in a well-ventilated area.
• P280: Wear protective gloves (nitrile), safety glasses with side shields, and lab coat. Consider double-gloving.
• P301+P310: IF SWALLOWED: Immediately call a POISON CENTER or physician.
• P302+P352: IF ON SKIN: Wash with plenty of soap and water.
• P304+P340: IF INHALED: Remove person to fresh air and keep comfortable for breathing.
• P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present and easy to do. Continue rinsing.
• P308+P313: IF exposed: Get medical advice/attention.
• P330: Rinse mouth if swallowed.
• P403+P233: Store in a well-ventilated place. Keep container tightly closed.
• P405: Store locked up.
• P501: Dispose of contents/container in accordance with local, regional, and national regulations.
• First Aid Measures:
• Inhalation: Remove to fresh air immediately. If breathing difficult, administer oxygen and seek medical attention.
• Skin Contact: Immediately wash with plenty of soap and water for at least 15 minutes. Remove contaminated clothing. Seek medical advice if irritation or rash develops.
• Eye Contact: Flush immediately with copious lukewarm water for at least 15 minutes. Remove contact lenses if possible. Seek medical attention immediately.
• Ingestion: Rinse mouth. Do NOT induce vomiting. Give water to drink if conscious. Call a POISON CENTER immediately.
• Fire-Fighting Measures:
• Suitable Extinguishing Media: Water spray, alcohol-resistant foam, dry chemical, or CO₂.
• Special Hazards: Combustion may produce highly toxic fumes including HCl (hydrogen chloride), chlorine gas (Cl₂), CO, and NOₓ. Hydrogen chloride and chlorine are extremely corrosive and toxic.
• Protective Equipment: Wear self-contained breathing apparatus (SCBA) and full protective clothing.
• Spill Response:
• Avoid dust generation. Sweep up and place in a suitable closed container for disposal. Do NOT use combustible materials for cleanup. Do not allow entry to drains or waterways. Ventilate area after cleanup.
• Handling & Storage:
• Handle in fume hood ONLY. Keep container closed when not in use. Store at -20°C, protected from light and moisture. Keep away from strong oxidizers, strong bases, and heat sources.
• Hazardous Decomposition Products: Hydrogen chloride (HCl), chlorine gas (Cl₂), nitrogen oxides (NOₓ), carbon monoxide (CO).
• Intended Use: For laboratory research and development ONLY. Not for human or veterinary therapeutic, diagnostic, or food use. Handle as a potentially bioactive, cytotoxic, and organochlorine compound.
