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| 25mg |
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Purity: ≥98%
Pamapimod (formerly known as R-1503; Ro-4402257) is a novel and selective mitogen-activated protein kinase (MAPK) inhibitor with immunomodulatory and anti-inflammatory properties. It has an IC50 of 14 and 480 nM for p38α and p38β enzymatic activity, respectively, and has no effect on the p38γ or p38δ isoforms. Pamapimod showed only four kinase bindings when profiled across 350 kinases, indicating a superb selectivity profile. Pamapimod was also discovered to inhibit JNK (c-Jun NH(2)-terminal kinase), but not p38. Additionally, LPS (lipopolysaccharide)-induced monocyte TNFα and IL-1β production was inhibited by pamapimod.
| Targets |
p38α (IC50 = 14 nM); p38α (Ki = 1.3 nM); p38β (IC50 = 480 nM); p38β (Ki = 120 nM)
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| ln Vitro |
Pamapimod inhibited p38 but did not appear to inhibit JNK. Additionally, tumor necrosis factor (TNF) α production by monocytes stimulated by lipopolysaccharide (LPS), interleukin (IL)-1β production in human whole blood, and spontaneous TNFα production by synovial explants from RA patients were all reduced by pamapimod[1].
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| ln Vivo |
Pamapimod, at 50 mg/kg or more, decreased clinical signs of inflammation and bone loss in murine collagen-induced arthritis. Pamapimod, which increased tolerance to pressure in a dose-dependent manner in a rat model of hyperalgesia, raises the possibility that p38 plays a significant role in pain brought on by inflammation. Pamapimod prevents synovial explants from RA patients from producing TNFα on their own. Pamapimod also prevented rodents from producing TNFα and IL-6 when LPS and TNFα were present[1].
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| Cell Assay |
THP-1 cells in log phase were collected by centrifugation and resuspended in RPMI 1640 containing 5.5×10-5 M 2-mercaptoethanol and 10% fetal bovine serum to a final cell concentration of 2.5×106 cells/ml. Before adding cells, pamapimod dilutions were predispensed in 25 μl aliquots into 96-well plates with a rounded bottom. Six half-log serial dilutions were performed starting with a concentration of 100 μM in 5% dimethyl sulfoxide. The final concentration of dimethyl sulfoxide was 0.5% following the addition of 200 μl of cell suspension and 25 μl of medium containing 5 μg/ml LPS. The final concentration of LPS was 500 ng/ml after compounds were diluted a further 10 times. Before adding LPS (or medium for control samples without LPS), the cell suspensions and compound dilutions were mixed and incubated for 30 min at 37°C in a humidified atmosphere of 5% CO2. Plates were then centrifuged to remove the cells after being incubated for 2 hours after the addition of LPS. Until the TNF-α content was analyzed, cell supernatants were kept at 4°C. ELISA was used to calculate the levels of TNF-α. There were measured cytokine concentrations.
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| Animal Protocol |
BALB/c mice
25, 50, 100, 150 mg/kg oral administration |
| References |
| Molecular Formula |
C19H20F2N4O4
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| Molecular Weight |
406.38
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| Exact Mass |
406.15
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| Elemental Analysis |
C, 56.15; H, 4.96; F, 9.35; N, 13.79; O, 15.75
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| CAS # |
449811-01-2
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| Related CAS # |
Pamapimod-d4;1246814-57-2
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| Appearance |
white solid powder
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| SMILES |
CN1C2=NC(=NC=C2C=C(C1=O)OC3=C(C=C(C=C3)F)F)NC(CCO)CCO
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| InChi Key |
JYYLVUFNAHSSFE-UHFFFAOYSA-N
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| InChi Code |
nChI=1S/C19H20F2N4O4/c1-25-17-11(10-22-19(24-17)23-13(4-6-26)5-7-27)8-16(18(25)28)29-15-3-2-12(20)9-14(15)21/h2-3,8-10,13,26-27H,4-7H2,1H3,(H,22,23,24)
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| Chemical Name |
6-(2,4-difluorophenoxy)-2-(1,5-dihydroxypentan-3-ylamino)-8-methylpyrido[2,3-d]pyrimidin-7-one
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| Synonyms |
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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 |
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| 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) |
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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 | 2.4608 mL | 12.3038 mL | 24.6075 mL | |
| 5 mM | 0.4922 mL | 2.4608 mL | 4.9215 mL | |
| 10 mM | 0.2461 mL | 1.2304 mL | 2.4608 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.
 (A–C) Percentages of patients achieving a response according to the American College of Rheumatology criteria with improvements of 20%, 50% and 70% (ACR20, ACR50 and ACR70, respectively).Ann Rheum Dis.2010 Feb;69(2):364-7. |
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Median change from baseline C-reactive protein.Ann Rheum Dis.2010 Feb;69(2):364-7. |
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