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| 1mg |
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| Targets |
Forigerimod targets CD4 T cells and modulates their activity. It is a phosphorylated peptide derived from U1-70K snRNP, an autoantigen in SLE. Forigerimod acts directly on chaperone-mediated autophagy (CMA), correcting autophagy defects that occur in autoimmune conditions. It corrects cellular content and distribution in salivary glands and restores normal autophagy processes, thereby reducing autoimmunity.
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| ln Vitro |
In vitro, Forigerimod TFA acts as a CD4 T-cell modulator and potently inhibits autophagy. It is a 21-amino-acid fragment of the U1 small nuclear ribonucleoprotein 70 kDa that is phosphorylated at Ser140. The TFA salt form enhances peptide solubility for cell-based assays. It corrects defective autophagy processes and restores normal cellular function in autoimmune cell models.
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| ln Vivo |
Forigerimod TFA (P140) (iv; 100 μg in 100 μL saline per mouse) works directly on chaperone-mediated autophagy, protecting MRL/lpr mice against abnormalities in autophagy that arise in the salivary glands and cellular infiltration[4].
In vivo, Forigerimod TFA (P140; i.v.; 100 ug in 100 uL saline per mouse, single dose) directly acts on chaperone-mediated autophagy (CMA), rescuing MRL/lpr mice from cellular infiltration and autophagy defects occurring in salivary glands. It corrects the cell content and distribution in MRL/lpr salivary glands and corrects defective autophagy processes. The peptide has shown efficacy in MRL/lpr mouse models of SLE. |
| Enzyme Assay |
Cell-free binding assays are not typically performed since Forigerimod acts intracellularly on autophagy pathways rather than binding to a purified receptor. For autophagy studies, the compound can be used in cell lysates to study CMA components. For protein-protein interaction assays, use purified CMA components (LAMP2A, Hsc70) and add Forigerimod TFA (1-100 uM) to study binding interactions by surface plasmon resonance or co-immunoprecipitation followed by Western blot detection of the phosphorylated peptide.
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| Cell Assay |
Culture MRL/lpr mouse-derived cells or human cell lines relevant to autoimmunity (e.g., Jurkat T cells, Raji B cells, or primary human PBMCs) in RPMI-1640 with 10% FBS. Treat cells with Forigerimod TFA at concentrations ranging from 0.1-100 uM for 24-72 hours. Assess autophagy by Western blot for LC3-II/I ratio and p62/SQSTM1 levels. Measure chaperone-mediated autophagy (CMA) activity using reporter substrates. Assess cell viability by MTT. For CD4 T-cell modulation, isolate CD4+ T cells and measure cytokine production (IL-17, IFN-gamma, IL-4) by ELISA after peptide treatment.
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| Animal Protocol |
Animal/Disease Models: MRL/lpr mice[4]
Doses: 100 μg in 100 μL saline per mouse Route of Administration: intravenous (iv) administration, single Experimental Results: Corrected the cell content and distribution in MRL/lpr salivary glands. Corrected the defective of autophagy processes in SGs of MRL/lpr mice. For SLE models, use MRL/lpr mice (autoimmune lupus-prone). Administer Forigerimod TFA (P140) via intravenous injection at 100 ug in 100 uL saline per mouse (single dose). After treatment, sacrifice mice and harvest salivary glands (SGs). Prepare tissue sections for immunohistochemistry to assess cellular infiltration (CD4, CD8, B220 staining) and H&E staining for histopathological scoring. Isolate lysates from salivary glands and perform Western blot for autophagy markers (LC3-II, p62, LAMP2A). Alternatively, use a multi-dose regimen (weekly injections for 4-8 weeks) to assess disease-modifying effects. Monitor disease progression by measuring autoantibody levels (anti-dsDNA, anti-nuclear antibodies) in serum by ELISA. Assess proteinuria and renal histopathology for lupus nephritis. For efficacy studies, administer peptide prophylactically or therapeutically and compare to vehicle-treated controls. |
| ADME/Pharmacokinetics |
Forigerimod is a 21-amino-acid phosphorylated peptide (MW: approximately 2639 for the free base). As a peptide, it is subject to proteolytic degradation. The TFA salt enhances water solubility. For intravenous administration, dissolve in saline (100 ug per 100 uL per mouse). The TFA counterion is often used in peptide formulations to improve stability. Storage: Powder at -80degC (2 years) or -20degC (1 year); in solvent at -80degC (6 months) or -20degC (1 month), sealed, under nitrogen, away from light and moisture. DMSO and water solubility: 100 mg/mL.
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| Toxicity/Toxicokinetics |
The toxicity profile of Forigerimod TFA is favorable based on preclinical and clinical studies. In a Phase IIb clinical trial (n=126 SLE patients), Forigerimod was well-tolerated with a safety profile similar to placebo. No severe adverse events or dose-limiting toxicities were reported in clinical studies at therapeutic doses. In MRL/lpr mouse studies, no significant acute toxicity was observed at 100 ug/mouse (approximately 4 mg/kg). The compound is not genotoxic or cytotoxic at therapeutic concentrations. The TFA salt may cause mild irritation. Standard laboratory precautions (gloves, lab coat, safety glasses) should be used.
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| References |
[1]. Aikaterini Thanou, et al. Treatment of systemic lupus erythematosus: new therapeutic avenues and blind alleys.
[2]. Sean Robinson, et al. Potential for Antigen-Specific Tolerizing Immunotherapy in Systematic Lupus Erythematosus. Front Immunol. 2021 Jul 16;12:654701. [3]. Robert Zimmer, et al. Lupuzor/P140 peptide in patients with systemic lupus erythematosus: a randomised, double-blind, placebo-controlled phase IIb clinical trial. Ann Rheum Dis. 2013 Nov;72(11):1830-5. [4]. Baihui Li, et al. Rescue of autophagy and lysosome defects in salivary glands of MRL/lpr mice by a therapeutic phosphopeptide. J Autoimmun. 2018 Jun;90:132-145. |
| Additional Infomation |
Forigerimod TFA (IPP-201101 TFA) is also known as P140, Lupuzor, or IPP-201101. The peptide is derived from the spliceosomal U1-70K snRNP autoantigen. A Phase IIb double-blind, randomized, placebo-controlled clinical trial (NCT02504645) in SLE patients demonstrated efficacy and safety, with significant improvement in disease activity as measured by CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index). The compound is for research use only and is not approved for therapeutic use in humans.
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| Molecular Formula |
C117H181N34O32PS.XC2HF3O2
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| Related CAS # |
Forigerimod;497156-60-2
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| Appearance |
Typically exists as solid at room temperature
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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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 DMSO :~100 mg/mL
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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.) |
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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