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| Targets |
Splice variants: ICAM-1 (intercellular adhesion molecule-1, also known as CD54). ICAM-1 is a cell surface glycoprotein expressed on endothelial cells, immune cells, and other cell types. It plays a critical role in the adhesion and transendothelial migration of leukocytes (white blood cells) from the bloodstream into inflamed tissues. By binding to its counter-receptors LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) on leukocytes, ICAM-1 facilitates immune cell trafficking to sites of inflammation. Alicaforsen is an antisense oligonucleotide that hybridizes to ICAM-1 mRNA, preventing its translation and reducing ICAM-1 protein levels.
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| ln Vitro |
Alicaforsen is a 20-base phosphorothioate antisense oligonucleotide complementary to human ICAM-1 mRNA. In vitro, Alicaforsen inhibits ICAM-1 production by binding to its target mRNA and inducing RNase H-mediated degradation, leading to reduced ICAM-1 protein expression. This reduces leukocyte adhesion and migration in in vitro models of inflammation. The (R/S)-racemate is the mixed configuration used for research purposes.
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| ln Vivo |
In vivo, Alicaforsen has been evaluated in clinical trials for inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, as well as for other inflammatory conditions such as pouchitis and psoriasis. In animal models of inflammation, antisense inhibition of ICAM-1 reduces leukocyte infiltration into inflamed tissues and ameliorates disease severity. In enema formulations, Alicaforsen is administered locally to the colon, achieving high local concentrations with minimal systemic exposure, making it attractive for treating IBD.
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| Enzyme Assay |
A standard approach for assessing antisense oligonucleotide target engagement does not involve traditional enzyme activity assays. However, cellular uptake and target mRNA binding can be assessed using fluorescently-labeled Alicaforsen. In non-cell systems, surface plasmon resonance (SPR) can be used to measure the binding affinity of Alicaforsen to complementary RNA oligonucleotides representing the ICAM-1 target sequence. A biotinylated RNA target is immobilized on a sensor chip, and varying concentrations of Alicaforsen are flowed over the chip. Association and dissociation rates are measured to calculate the Kd.
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| Cell Assay |
For cellular activity, human umbilical vein endothelial cells (HUVECs) or other ICAM-1-expressing cells (e.g., epithelial cells, leukocytes) are cultured in 6- or 12-well plates and treated with Alicaforsen or the (R/S)-racemate as control at concentrations of 0.1-10 uM for 24-72 hours. Cells are stimulated with pro-inflammatory cytokines (TNF-alpha, IL-1beta, LPS, 1-10 ng/mL) to induce ICAM-1 expression. After treatment, cells are harvested, and ICAM-1 mRNA is quantified by qRT-PCR. ICAM-1 protein levels are assessed by Western blot or by flow cytometry using an anti-ICAM-1 antibody. Reduced ICAM-1 expression indicates successful antisense activity. (R/S)-Alicaforsen is used as a control in these assays.
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| Animal Protocol |
Alicaforsen is typically administered locally via enema for the treatment of ulcerative colitis, rather than systemically. In animal models, it may be administered intravenously or intraperitoneally. For preclinical studies, the compound can be dissolved in sterile saline and administered IV or IP. A typical study design would involve administering Alicaforsen to a rodent model of colitis (e.g., DSS-induced colitis or TNBS-induced colitis) at doses of 1-10 mg/kg daily for 7-14 days. Disease activity index (DAI), colon length, and histological scores are assessed. ICAM-1 expression in colon tissue is measured by immunohistochemistry or qRT-PCR. (R/S)-Alicaforsen is used as a research control.
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| ADME/Pharmacokinetics |
As a 20-base antisense oligonucleotide, Alicaforsen has a molecular weight of approximately 6368.00. It is soluble in water (H2O) at ~100 mg/mL (~15.70 mM) and in DMSO. The phosphorothioate backbone provides increased resistance to nuclease degradation compared to natural oligonucleotides. Plasma half-life is typically 30-60 minutes to a few hours, with extensive tissue distribution. For topical administration (enema), systemic absorption is minimal, with high local concentrations achieved in the colon. For in vivo formulation, vehicles such as 10% DMSO + 5% Tween 80 + 85% saline, or 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline, or 10% DMSO + 90% corn oil can be used.
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| Toxicity/Toxicokinetics |
In clinical trials, Alicaforsen has been generally well-tolerated. The most common adverse events include mild gastrointestinal symptoms (e.g., nausea, diarrhea) and local irritation at the injection or enema site. Systemic antisense oligonucleotides may cause flu-like symptoms, injection site reactions, and mild increases in liver enzymes. No significant off-target effects, hematologic toxicity, or genotoxicity have been reported at therapeutic doses. As an antisense oligonucleotide with a specific sequence, off-target effects are minimized through careful sequence design. Preclinical toxicology studies have shown an acceptable safety margin.
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| References | |
| Additional Infomation |
Alicaforsen (ISIS-2302) is a 20-base phosphorothioate antisense oligonucleotide targeting ICAM-1 mRNA. It has been investigated in Phase 2 and Phase 3 clinical trials for inflammatory bowel disease (ulcerative colitis, Crohn's disease), pouchitis, psoriasis, and other inflammatory conditions. In a randomized, double-masked, placebo-controlled study, Alicaforsen enema showed clinical benefit in patients with active ulcerative colitis. While development has not progressed to FDA approval as of current publicly available information, the compound has provided valuable proof-of-concept for antisense therapy targeting adhesion molecules in inflammatory diseases. The (R/S)-racemate is the mixed configuration form for research purposes. This product is for research use only and is not FDA-approved for human therapy.
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| Molecular Weight |
6368.00
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| Related CAS # |
Alicaforsen;185229-68-9;Alicaforsen sodium;331257-52-4
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| Appearance |
White to off-white solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O :~100 mg/mL (~15.70 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.1570 mL | 0.7852 mL | 1.5704 mL | |
| 5 mM | 0.0314 mL | 0.1570 mL | 0.3141 mL | |
| 10 mM | 0.0157 mL | 0.0785 mL | 0.1570 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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