| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
IL-6 IL-8 IL1R1 8 nM (IC50)
Human type I interleukin-1 receptor (IL1R1), the primary signaling receptor for IL-1alpha and IL-1beta. AF12198 is a specific peptide antagonist that binds to IL1R1 with high affinity, preventing IL-1 from binding and blocking downstream NF-kappaB and MAPK signaling pathways. |
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| ln Vitro |
AF12198 has an IC50 of 8.0 nM, which is approximately equivalent to IL-1ra's 4.0 nM for type I receptors when it comes to competition for binding to 125I-IL-1α [1]. In heparinized human primate blood, AF12198 (0-5 ng; 8 hours) suppresses IL-6 production with an IC50 of 15 μM and IL-1ra with an IC50 of 2 nM. Similarly, with blood from cynomolgus monkeys, the IC50 values for AF12198 and IL-1ra were 17 μM and 30 nM, respectively. Moreover, neither AF12198 nor IL-1RA by themselves were able to produce IL-6 in human or cynomolgus monkey blood [1].
In vitro, AF12198 blocks IL-1-induced IL-8 production (IC50=25 nM) and ICAM-1 expression (IC50=9 nM) in human cells. It inhibits IL-1alpha binding to the type I IL-1 receptor with an IC50 of 1.9 nM. In heparinized human and cynomolgus monkey blood, AF12198 inhibits IL-6 induction with IC50 values of 15 uM and 17 uM, respectively, though its potency is lower than IL-1ra. |
| ln Vivo |
Rats with acute lung inflammation were given AF12198 (intravenous infusion; 16 mg/kg; 30 minutes prior to LPS intravenous injection), which decreased the number of inflamed rats by 4 hours (32.6%) and 12 minutes after the injection. 24-hour period (65.3%) and hourly (50.1%)[2].
In a rat model of LPS-induced acute lung inflammation, intravenous infusion of AF12198 (16 mg/kg, 30 min before LPS) significantly inhibited the elevation of lung myeloperoxidase (MPO) activity over time: 32.6% at 4h, 50.1% at 12h, and 65.3% at 24h, indicating effective reduction of neutrophil infiltration and lung inflammation. |
| Enzyme Assay |
For receptor binding, a radioligand binding assay is used: membranes from cells expressing human IL1R1 are incubated with [125I]-IL-1alpha in the presence of serially diluted AF12198 (0.1-1000 nM). Bound radioactivity is measured by filtration and scintillation counting to calculate the IC50 for displacement.
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| Cell Assay |
Human peripheral blood mononuclear cells (PBMCs) or endothelial cells are stimulated with IL-1beta (1 ng/mL) in the presence of serially diluted AF12198 (0.1-1000 nM) for 24 h. Supernatants are collected, and IL-8 levels are measured by ELISA. Alternatively, ICAM-1 surface expression on endothelial cells is quantified by flow cytometry after 6-24 h of stimulation. The IC50 is calculated.
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| Animal Protocol |
Animal/Disease Models: Male Wistar rats[2]
Doses: 16 mg/kg Route of Administration: intravenous (iv) infusion; 30 min before LPS intravenous (iv) injection Experimental Results: diminished pulmonary microvascular leakage in rats. Male Sprague-Dawley rats receive intratracheal LPS (5 mg/kg) to induce acute lung inflammation. AF12198 is administered via intravenous infusion (16 mg/kg) 30 minutes prior to LPS challenge. At 4, 12, and 24 hours after LPS, animals are sacrificed, and lung tissue is harvested for MPO activity measurement. The percentage inhibition of MPO activity is calculated relative to vehicle-treated controls. |
| ADME/Pharmacokinetics |
AF12198 is a peptide with a molecular weight of 1895.14 g/mol and a formula of C96H123N19O22. It is supplied as a powder, soluble in DMSO or aqueous buffers. Detailed PK parameters are not publicly available. As a peptide, it is likely to have poor oral bioavailability and a short plasma half-life, requiring IV or IP administration for in vivo studies.
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| Toxicity/Toxicokinetics |
Detailed toxicological data are not publicly available. In animal studies, AF12198 (16 mg/kg, IV) was well-tolerated with no reported adverse effects. As a selective IL1R1 antagonist, potential toxicities may include increased susceptibility to infections due to blockade of IL-1-mediated immune responses.
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| References |
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| Additional Infomation |
AF12198 is a research peptide not approved for clinical use. It was first described in J Biol Chem (1996 Nov 29;271(48):30517-23) and has been used in studies to understand the role of the type I IL-1 receptor in inflammation. It is used as a tool to selectively block IL-1 signaling in human cells, though its poor activity against murine IL1R1 limits its use in standard mouse models.
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| Molecular Formula |
C96H123N19O22
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|---|---|
| Molecular Weight |
1895.12
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| Exact Mass |
1893.91
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| CAS # |
185413-30-3
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| PubChem CID |
16135237
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| Appearance |
White to off-white solid powder
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| Density |
1.354 g/cm3
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| LogP |
5.639
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| Hydrogen Bond Donor Count |
20
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| Hydrogen Bond Acceptor Count |
22
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| Rotatable Bond Count |
48
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| Heavy Atom Count |
137
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| Complexity |
4200
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| Defined Atom Stereocenter Count |
15
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| SMILES |
C[C@H]([C@@H](C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CC2=CNC3=CC=CC=C32)C(=O)N[C@@H](CC4=CC=C(C=C4)O)C(=O)N[C@@H](CCC(=O)N)C(=O)N5CC[C@H]5C(=O)N[C@@H](CC6=CC=C(C=C6)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N7CCC[C@H]7C(=O)N[C@@H](CC(C)C)C(=O)N)NC(=O)[C@H](CC8=CNC9=CC=CC=C98)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)C)O
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| InChi Key |
VASLMBMCJADVGR-XQDBXYBUSA-N
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| InChi Code |
InChI=1S/C96H123N19O22/c1-51(2)41-69(83(98)124)107-92(133)77-24-16-38-113(77)95(136)75(42-52(3)4)111-84(125)53(5)102-86(127)71(44-57-25-29-61(118)30-26-57)110-93(134)78-37-40-115(78)94(135)68(33-35-79(97)120)106-88(129)72(45-58-27-31-62(119)32-28-58)108-89(130)73(46-59-48-99-65-21-13-11-19-63(59)65)104-80(121)50-101-91(132)76-23-15-39-114(76)96(137)82(54(6)116)112-90(131)74(47-60-49-100-66-22-14-12-20-64(60)66)109-85(126)67(34-36-81(122)123)105-87(128)70(103-55(7)117)43-56-17-9-8-10-18-56/h8-14,17-22,25-32,48-49,51-54,67-78,82,99-100,116,118-119H,15-16,23-24,33-47,50H2,1-7H3,(H2,97,120)(H2,98,124)(H,101,132)(H,102,127)(H,103,117)(H,104,121)(H,105,128)(H,106,129)(H,107,133)(H,108,130)(H,109,126)(H,110,134)(H,111,125)(H,112,131)(H,122,123)/t53-,54+,67-,68-,69-,70-,71-,72-,73-,74-,75-,76-,77-,78-,82-/m0/s1
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| Chemical Name |
(4S)-4-[[(2S)-2-acetamido-3-phenylpropanoyl]amino]-5-[[(2S)-1-[[(2S,3R)-1-[(2S)-2-[[2-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]carbamoyl]azetidin-1-yl]-1,5-dioxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-2-oxoethyl]carbamoyl]pyrrolidin-1-yl]-3-hydroxy-1-oxobutan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid
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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) |
DMSO: 100 mg/mL (52.77 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (1.32 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (1.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.5277 mL | 2.6384 mL | 5.2767 mL | |
| 5 mM | 0.1055 mL | 0.5277 mL | 1.0553 mL | |
| 10 mM | 0.0528 mL | 0.2638 mL | 0.5277 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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