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| Other Sizes |
| Targets |
D-JNKI-1 targets c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase (MAPK) family involved in stress responses, apoptosis, and inflammation. The compound acts as a highly potent and cell-permeable peptide inhibitor of JNK. It is a cell-penetrating peptide that can cross cell membranes to inhibit intracellular JNK signaling.
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| ln Vitro |
D-JNKI-1 (AM-111; 1 μM-1 mM) therapy inhibits apoptosis and loss of hair cells subjected to neomycin [1].
In vitro, D-JNKI-1 (1 microM-1 mM) treatment prevents apoptosis and loss of neomycin-exposed hair cells. The compound (10 microM) prevents nearly all hair cell death and permanent hearing loss induced by neomycin ototoxicity. It is a highly potent JNK inhibitor with cell-permeable properties. |
| ln Vivo |
In the guinea pig cochlea's scala tympani, D-JNKI-1 (AM-111; 10 μM) virtually completely stops hair cell death and irreversible hearing loss brought on by neomycin ototoxicity. In a dose-dependent manner, topical use of D-JNKI-1 also prevents irreversible hearing loss brought on by acoustic trauma [1]. In rat brain mitochondria, D-JNKI-1 (0.3 mg/kg, i.p.) reverses these pathogenic events and nearly entirely eliminates cytochrome c release and PARP breakage [2]. D-JNKI-1 (1 μg/kg, sc) significantly decreased the expression of CD4+ and CD8+ cells in mice as well as the disease activity index in mice [3].
In vivo, D-JNKI-1 (10 microM) prevents nearly all hair cell death and permanent hearing loss induced by neomycin ototoxicity in the scala tympani of the guinea pig cochlea. The compound has shown efficacy in animal models of hearing loss and is being investigated for inner ear protection. Further in vivo studies are documented in the published literature. |
| Enzyme Assay |
The in vitro JNK inhibition assay uses recombinant JNK kinase and a peptide substrate with ATP. Kinase activity is measured by quantifying phosphorylated substrate using radioactive ATP incorporation, fluorescence polarization, or luminescence-based methods. IC₅0 values are calculated from dose-response curves. Cell permeability is assessed by measuring intracellular compound accumulation or downstream signaling inhibition in cells.
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| Cell Assay |
For in vitro cell-based assays, hair cells or other cell types are cultured and treated with D-JNKI-1 at various concentrations (1 microM-1 mM). Apoptosis is assessed using caspase activity assays, Annexin V staining, or TUNEL staining. JNK phosphorylation is measured by Western blot to confirm target inhibition. Cells are maintained under standard culture conditions and experiments are typically performed in triplicate.
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| Animal Protocol |
In vivo animal studies for D-JNKI-1 typically involve guinea pig models of neomycin-induced ototoxicity. The compound is administered via scala tympani injection at 10 microM. Hair cell survival is assessed by histological analysis. Hearing function is measured by auditory brainstem response (ABR) testing. Efficacy is evaluated by preservation of hair cells and hearing function. Studies in mouse models have also been performed.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of D-JNKI-1 indicate cell-permeable properties. The compound has molecular weight 3822.44 and molecular formula C1₆4H2₈₆N₆₆O40. It is soluble in DMSO (≥90 mg/mL) and water (≥50 mg/mL). Storage: powder at -20degC for 3 years; 4degC for 2 years; in solvent at -80degC for 6 months or -20degC for 1 month.
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| Toxicity/Toxicokinetics |
Toxicological data for D-JNKI-1 are not extensively documented. As a research peptide, standard safety precautions should be observed. The compound is for laboratory use only and not intended for human therapeutic applications. JNK inhibitors as a class may have potential effects on stress responses and apoptosis. Comprehensive toxicity profiling would be required for therapeutic development.
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| References |
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| Additional Infomation |
Brimapitide is being studied in the clinical trial NCT01570205 (a study of the safety, tolerability, and pharmacokinetics of single intravenous infusions of 10, 40, and 80 µg/kg XG-102 in healthy volunteers).
D-JNKI-1 (CAS# 1445179-97-4) is a highly potent and cell-permeable peptide inhibitor of JNK. It prevents neomycin-induced hair cell apoptosis and hearing loss. The compound is also known as AM-111, XG-102, and Brimapitide. It is used in neuroscience and ototoxicity research and is not approved for clinical use. |
| Molecular Formula |
C164H286N66O40
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|---|---|
| Molecular Weight |
3822.44
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| Exact Mass |
3821.24
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| CAS # |
1445179-97-4
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| PubChem CID |
90479374
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| Appearance |
White to off-white solid powder
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| LogP |
-20.9
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| Hydrogen Bond Donor Count |
64
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| Hydrogen Bond Acceptor Count |
53
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| Rotatable Bond Count |
135
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| Heavy Atom Count |
270
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| Complexity |
9220
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| Defined Atom Stereocenter Count |
32
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| SMILES |
C[C@@H]([C@H](C(=O)N[C@H]([C@H](C)O)C(=O)N1CCC[C@@H]1C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H](CCCCN)C(=O)N2CCC[C@@H]2C(=O)N[C@H](CCCNC(=N)N)C(=O)N3CCC[C@@H]3C(=O)N4CCC[C@@H]4C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H](CCC(=O)N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H](CCCNC(=N)N)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCCN)C(=O)N[C@H](CCCNC(=N)N)C(=O)NCC(=O)N)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](CC(=O)N)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](CC5=CC=CC=C5)NC(=O)[C@H]6CCCN6C(=O)[C@@H](CCC(=O)N)NC(=O)[C@@H](C(C)C)NC(=O)[C@H]7CCCN7C(=O)[C@@H](CCCNC(=N)N)NC(=O)[C@@H](CO)NC(=O)[C@@H](CCC(=O)N)NC(=O)[C@@H](CC(=O)O)N)O
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| InChi Key |
BAAXVYBAMNDCIB-BMCUWHFPSA-N
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| InChi Code |
InChI=1S/C164H286N66O40/c1-84(2)77-106(217-139(254)108(79-89-33-10-9-11-34-89)220-146(261)112-48-28-72-226(112)153(268)105(55-58-119(171)236)216-148(263)123(86(5)6)222-147(262)115-51-29-73-227(115)151(266)103(45-25-69-199-163(188)189)214-142(257)110(83-231)221-137(252)100(53-56-117(169)234)202-126(241)90(168)80-122(239)240)138(253)219-109(81-120(172)237)140(255)218-107(78-85(3)4)141(256)223-124(87(7)232)149(264)224-125(88(8)233)155(270)229-75-31-50-114(229)144(259)212-99(44-24-68-198-162(186)187)135(250)213-102(37-14-17-61-167)150(265)225-71-27-47-111(225)145(260)215-104(46-26-70-200-164(190)191)152(267)230-76-32-52-116(230)154(269)228-74-30-49-113(228)143(258)211-98(43-23-67-197-161(184)185)134(249)208-95(40-20-64-194-158(178)179)131(246)207-97(42-22-66-196-160(182)183)133(248)210-101(54-57-118(170)235)136(251)209-96(41-21-65-195-159(180)181)132(247)206-94(39-19-63-193-157(176)177)130(245)205-93(36-13-16-60-166)129(244)204-92(35-12-15-59-165)128(243)203-91(38-18-62-192-156(174)175)127(242)201-82-121(173)238/h9-11,33-34,84-88,90-116,123-125,231-233H,12-32,35-83,165-168H2,1-8H3,(H2,169,234)(H2,170,235)(H2,171,236)(H2,172,237)(H2,173,238)(H,201,242)(H,202,241)(H,203,243)(H,204,244)(H,205,245)(H,206,247)(H,207,246)(H,208,249)(H,209,251)(H,210,248)(H,211,258)(H,212,259)(H,213,250)(H,214,257)(H,215,260)(H,216,263)(H,217,254)(H,218,255)(H,219,253)(H,220,261)(H,221,252)(H,222,262)(H,223,256)(H,224,264)(H,239,240)(H4,174,175,192)(H4,176,177,193)(H4,178,179,194)(H4,180,181,195)(H4,182,183,196)(H4,184,185,197)(H4,186,187,198)(H4,188,189,199)(H4,190,191,200)/t87-,88-,90+,91+,92+,93+,94+,95+,96+,97+,98+,99+,100+,101+,102+,103+,104+,105+,106+,107+,108+,109+,110+,111+,112+,113+,114+,115+,116+,123+,124+,125+/m0/s1
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| Chemical Name |
(3R)-3-amino-4-[[(2R)-5-amino-1-[[(2R)-1-[[(2R)-1-[(2R)-2-[[(2R)-1-[[(2R)-5-amino-1-[(2R)-2-[[(2R)-1-[[(2R)-1-[[(2R)-4-amino-1-[[(2R)-1-[[(2R,3S)-1-[[(2R,3S)-1-[(2R)-2-[[(2R)-1-[[(2R)-6-amino-1-[(2R)-2-[[(2R)-1-[(2R)-2-[(2R)-2-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-5-amino-1-[[(2R)-1-[[(2R)-1-[[(2R)-6-amino-1-[[(2R)-6-amino-1-[[(2R)-1-[(2-amino-2-oxoethyl)amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]carbamoyl]pyrrolidine-1-carbonyl]pyrrolidin-1-yl]-5-carbamimidamido-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-hydroxy-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-5-carbamimidamido-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-4-oxobutanoic 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, 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) |
DMSO : ≥ 100 mg/mL (~26.16 mM)
H2O : ≥ 50 mg/mL (~13.08 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (0.65 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 (0.65 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (0.65 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 25 mg/mL (6.54 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. Solubility in Formulation 5: 50 mg/mL (13.08 mM) in Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.2616 mL | 1.3081 mL | 2.6161 mL | |
| 5 mM | 0.0523 mL | 0.2616 mL | 0.5232 mL | |
| 10 mM | 0.0262 mL | 0.1308 mL | 0.2616 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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