| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
p38α
p38alpha MAPK |
|---|---|
| ln Vitro |
With an IC50 value of 100 pM, emprumapimod (ARRY-797) suppresses the production of IL-6 in RPMI-8226 cells stimulated by LPS[1].
Emprumapimod is a selective p38alpha MAPK inhibitor that directly inhibits LPS‑induced IL‑6 production in RPMI‑8226 cells with an IC₅0 of 100 pM (0.1 nM). It also inhibits LPS‑induced production of other pro‑inflammatory cytokines. Its high potency and selectivity make it a valuable tool for studying p38alpha‑mediated inflammatory pathways. |
| ln Vivo |
Emprumapimod (ARRY-797) (30 mg/kg; oral) decreases the expression of p38 in RPMI-8226 xenografts and IL-6 (91%) and TNF-α (95%) in SCID-beige mice. In multiple myeloma (MM) xenograft models, phosphorylation of RPMI-8226 inhibits tumor growth (72%)[1]. In LmnaH222P/H222P mice, eremapimod (30 mg/kg; oral; twice daily for 4 weeks) inhibits the development of LV fractional shortening (FS) and left ventricular dilatation[2].
Emprumapimod has been evaluated in animal models of dilated cardiomyopathy and acute inflammatory pain. In these models, oral administration of emprumapimod demonstrated efficacy by suppressing p38alpha‑dependent inflammatory signaling. Detailed efficacy data is not publicly available. |
| Enzyme Assay |
For p38alpha enzymatic assays, recombinant p38alpha protein is incubated with emprumapimod (0.01‑1000 nM) and a substrate (e.g., ATF2 or MBP) in the presence of ATP. After incubation, substrate phosphorylation is quantified. Alternatively, a homogeneous time‑resolved fluorescence (HTRF) kinase assay can be used. IC₅0 values are calculated from dose‑response curves.
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| Cell Assay |
Emprumapimod is dissolved in DMSO and diluted to desired concentrations (final DMSO ≤0.1%). RPMI-8226 cells are pre‑treated with emprumapimod (0.01 nM - 1000 nM) for 1 h, then stimulated with LPS (1 ug/mL) for 6‑24 h. IL‑6 and TNF‑alpha levels in the culture supernatant are quantified by ELISA. p38alpha activity is confirmed by measuring phospho‑p38alpha or phospho‑ATF2 via Western blotting.
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| Animal Protocol |
Animal/Disease Models: LmnaH222P/H222P mice were[2]
Doses: 30 mg/kg Route of Administration: Administered orally by gavage starting when mice were 16 weeks of age and continuing until 20 weeks of age Experimental Results: There were significant increases in LVEDD and LVESD as well as a decrease in FS, a parameter directly proportional to the LV ejection fraction. Emprumapimod is formulated in a suitable vehicle (e.g., 0.5% methylcellulose or 10% DMSO, 40% PEG400, 5% Tween 80) and administered orally to mice or rats at doses of 1‑30 mg/kg (once or twice daily). Efficacy is assessed in models of LMNA‑associated dilated cardiomyopathy (by echocardiography and inflammatory marker measurement) or acute inflammatory pain (by measuring pain response). |
| ADME/Pharmacokinetics |
No detailed PK data for emprumapimod has been reported. As an orally bioavailable p38alpha inhibitor, it is expected to have favorable absorption, moderate plasma half‑life, and sufficient exposure to achieve target engagement. Detailed parameters such as half‑life, Cmax, and bioavailability are not publicly available.
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| Toxicity/Toxicokinetics |
No detailed toxicity data for emprapumapimod has been reported. As a p38alpha inhibitor, potential toxicities may include immunosuppression, hepatotoxicity, or gastrointestinal effects. High doses may cause off‑target kinase inhibition, but no toxicology studies have been published to date.
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| References |
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| Additional Infomation |
Emprumapimod is a potent, orally effective selective p38α mitogen-activated protein kinase inhibitor. It has been used in research for the treatment of dilated cardiomyopathy.
Emprumapimod (PF‑07265803; CAS: 765914-60-1; formula: C24H2₉F2N₅O3; MW: 473.52) is an orally active p38alpha MAPK inhibitor that has been investigated for dilated cardiomyopathy (LMNA gene‑associated) and acute inflammatory pain. It has not received FDA approval, and clinical trial data has not been published. It is currently a preclinical research tool. |
| Molecular Formula |
C24H29F2N5O3
|
|---|---|
| Molecular Weight |
473.515572309494
|
| Exact Mass |
473.223
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| CAS # |
765914-60-1
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| Related CAS # |
Emprumapimod hydrochloride
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| PubChem CID |
67411502
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| Appearance |
White to off-white solid powder
|
| LogP |
3.2
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| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
34
|
| Complexity |
698
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
N1(CC(C)C)C2=C(C=C(OC3=CC=C(F)C=C3F)C(C(N[C@H](C(N)=O)CCN(C)C)=O)=C2)C=N1
|
| InChi Key |
JOOOJNJPZINWHM-IBGZPJMESA-N
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| InChi Code |
InChI=1S/C24H29F2N5O3/c1-14(2)13-31-20-11-17(24(33)29-19(23(27)32)7-8-30(3)4)22(9-15(20)12-28-31)34-21-6-5-16(25)10-18(21)26/h5-6,9-12,14,19H,7-8,13H2,1-4H3,(H2,27,32)(H,29,33)/t19-/m0/s1
|
| Chemical Name |
N-[(2S)-1-amino-4-(dimethylamino)-1-oxobutan-2-yl]-5-(2,4-difluorophenoxy)-1-(2-methylpropyl)indazole-6-carboxamide
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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. |
| 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 (211.18 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.28 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 (5.28 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 (5.28 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1118 mL | 10.5592 mL | 21.1184 mL | |
| 5 mM | 0.4224 mL | 2.1118 mL | 4.2237 mL | |
| 10 mM | 0.2112 mL | 1.0559 mL | 2.1118 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.
Link: https://clinicaltrials.gov/ct2/show/NCT05286281
Conditions:HealthyLink: https://clinicaltrials.gov/ct2/show/NCT03439514
Conditions:Dilated Cardiomyopathy|Lamin A/C Gene MutationProducts are for research use only; We do not sell to patients
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