Physicochemical Properties
| Molecular Formula | C96H123N19O22 |
| Molecular Weight | 1895.12 |
| Exact Mass | 1893.91 |
| CAS # | 185413-30-3 |
| PubChem CID | 16135237 |
| Appearance | White to off-white solid powder |
| Density | 1.354 g/cm3 |
| LogP | 5.639 |
| Hydrogen Bond Donor Count | 20 |
| Hydrogen Bond Acceptor Count | 22 |
| Rotatable Bond Count | 48 |
| Heavy Atom Count | 137 |
| Complexity | 4200 |
| Defined Atom Stereocenter Count | 15 |
| 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 |
| InChi Key | VASLMBMCJADVGR-XQDBXYBUSA-N |
| 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 |
| 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 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | IL-6 IL-8 IL1R1 8 nM (IC50) |
| 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]. |
| 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]. |
| 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. |
| References |
[1]. Low level laser therapy (LLLT) decreases pulmonary microvascular leakage, neutrophil influx and IL-1beta levels in airway and lung from rat subjected to LPS-induced inflammation. Inflammation. [2]. AF12198, a novel low molecular weight antagonist, selectively binds the human type I interleukin (IL)-1 receptor and blocks in vivo responses to IL-1. J Biol Chem. 1996 Nov 29;271(48):30517-23. |
Solubility Data
| Solubility (In Vitro) | DMSO: 100 mg/mL (52.77 mM) |
| 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 |