| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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AMG-548 dihydrochloride is a novel, orally bioactive, potent and selective inhibitor of p38α with Ki of 0.5 nM. It exhibits some selectivity over p38β (Ki=36 nM) but >1000-fold selectivity against 36 other kinases, and it inhibits whole blood LPS-stimulated TNFα. AMG-548 has demonstrated effectiveness in both acute and chronic arthritis models.
| Targets |
p38α (Ki = 0.5 nM); p38β (Ki = 3.6 nM); p38δ (Ki = 2600 nM); p38γ (Ki = 4100 nM); dog p38α (Ki = 5.0 nM); JNK 1 (Ki = 11480nM); JNK 2 (Ki = 39 nM); JNK 3 (Ki = 61 nM); CK1
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| ln Vitro |
AMG-548 is >1000-fold selective for p38γ (Ki = 2600 nM) and p38δ (ki = 4100 nM). For JNK2 (ki=39 nM) and JNK3 (ki=61 nM), AMG-548 exhibits a modest level of selectivity. Additionally, AMG-548 is very effective in blocking TNFa (IC50=3 nM) and IL1b (IC50=7 nM) that are triggered by LPS, as well as TNFa-induced IL-8 (IC50=0.7 nM) and IL-1b-induced IL in whole blood human -6 (IC5050=1.3 nM)[1]. AMG-548 (10 μM) inhibits hDvl2 transition [2].
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| ln Vivo |
In rats, the F of AMG-548 was 62%, while in dogs, it was 47%. Rats have a t1/2 of 4.6 hours, while dogs have a t1/2 of 7.3 hours [1].
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| References |
[1]. Lee MR, et al. MAP kinase p38 inhibitors: clinical results and an intimate look at their interactions with p38alphaprotein. Curr Med Chem. 2005;12(25):2979-94.
[2]. Verkaar F, et al. Inhibition of Wnt/β-catenin signaling by p38 MAP kinase inhibitors is explained by cross-reactivity with casein kinase Iδ/ɛ. Chem Biol. 2011 Apr 22;18(4):485-94. |
| Molecular Formula |
C₂₉H₂₉CL₂N₅O
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|---|---|
| Molecular Weight |
461.22
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| Exact Mass |
461.22
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| Elemental Analysis |
C, 75.46; H, 5.90; N, 15.17; O, 3.47
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| CAS # |
864249-60-5
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| Related CAS # |
AMG-548 dihydrochloride;2518299-32-4;AMG-548 hydrochloride;2437438-16-7
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| Appearance |
Solid powder
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| SMILES |
CN1C(=O)C(=C(N=C1NC[C@H](CC2=CC=CC=C2)N)C3=CC=NC=C3)C4=CC5=CC=CC=C5C=C4.Cl.Cl
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| InChi Key |
WQZUYJOJJJERDI-WLOLSGMKSA-N
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| InChi Code |
InChI=1S/C29H27N5O.2ClH/c1-34-28(35)26(24-12-11-21-9-5-6-10-23(21)18-24)27(22-13-15-31-16-14-22)33-29(34)32-19-25(30)17-20-7-3-2-4-8-20;;/h2-16,18,25H,17,19,30H2,1H3,(H,32,33);2*1H/t25-;;/m0../s1
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| Chemical Name |
2-[[(2S)-2-amino-3-phenylpropyl]amino]-3-methyl-5-naphthalen-2-yl-6-pyridin-4-ylpyrimidin-4-one;dihydrochloride
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| Synonyms |
UNII-PGR0H531I4; AMG 548; AMG548; AMG-548
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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 |
| 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: ~62.5 mg/mL (~127.2mM)
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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 | 2.1682 mL | 10.8408 mL | 21.6816 mL | |
| 5 mM | 0.4336 mL | 2.1682 mL | 4.3363 mL | |
| 10 mM | 0.2168 mL | 1.0841 mL | 2.1682 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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