Cat. No.: HY-13241A

Ralimetinib

(Synonyms: LY2228820)

17 Cited Publications

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Based on 17 publication(s) in Google Scholar

Ralimetinib is an ATP-competitive p38α and p38β MAPK inhibitor with an IC₅₀ of 5.3 nmol/L against human p38α and an IC₅₀ of 3.2 nmol/L against human p38β. Ralimetinib slows tumor growth in preclinical in vivo cancer models, exhibits oral bioavailability in mice, and achieves sustained target inhibition for 4 to 8 h. Ralimetinib is applicable for research on melanoma, non-small cell lung cancer, ovarian cancer, glioma, multiple myeloma, breast cancer, renal cancer, and head and neck squamous cell carcinoma.

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Pureté: 98.58%
CAS No.: 862505-00-8
Formule: C₂₄H₂₉FN₆
Masse moléculaire:420.53

Stockage:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

Ralimetinib Chemical Structure

CAS No.: 862505-00-8

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Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Activité biologique
- Description
- IC₅₀ & Target
- In Vitro
- Parmacokinetics
- In Vivo
- Essai clinique
Chemical Information
Publications (17)
Solvant et solubilité
- In Vitro
- In Vivo
Pureté et documentation
Références
Help & FAQs
Classifications
Bioz

Activité biologique

Description

IC₅₀ & Target

p38β MAPK

3.2 nM (IC₅₀)

p38α MAPK

5.3 nM (IC₅₀)

Voir tous les produits spécifiques à Isoform p38 MAPK :

In Vitro

LY2228820 (1 nmol/L-20 μmol/L; 2 h pre-incubation, 30 min anisomycin stimulation) potently inhibits p38 pathway-mediated MK2 phosphorylation in anisomycin-stimulated RAW264.7 macrophages with an IC₅₀ of 35.3 nmol/L^[1].
LY2228820 (1 nmol/L-20 μmol/L; 0.5 h pre-incubation, 2 h LPS/IFN-γ stimulation) potently inhibits LPS/IFN-γ-induced TNF-α secretion in mouse peritoneal macrophages with an IC₅₀ of 6.3 nmol/L^[1].
LY2228820 (9.8 nmol/L-10 μmol/L; 1 h pre-incubation, 45 min anisomycin stimulation) selectively inhibits p38 pathway-mediated MK2 phosphorylation in anisomycin-stimulated HeLa cells at 9.8 nmol/L, with no off-target effects on JNK, ERK1/2, or their downstream substrates up to 10 μmol/L^[1].
LY2228820 (1 nmol/L-20 μmol/L; 30 min pre-incubation, 72 h LPS stimulation) inhibits LPS-induced CXCL8 secretion in A549 non-small cell lung cancer cells with an IC₅₀ of 144.9 nmol/L^[1].
LY2228820 inhibits p38 pathway-mediated MK2 phosphorylation in human peripheral blood mononuclear cells ex vivo with an IC₅₀ of 0.12 μmol/L^[1].
Ralimetinib (1.6 μM; two 72 h treatment intervals) induces apoptosis (19.12% Annexin positivity, 14.51% sub-G₁ phase) and modulates cell cycle distribution in SCC-25 cells, and enhances TGF-beta-1-induced Annexin positivity (24.23%) while causing G₂/S arrest in TGF-beta-1-pretreated SCC-25 cells^[2].
Ralimetinib (1.6 μM; two 72 h treatment intervals) inhibits phosphorylation of the p38 MAPK downstream target ATF2 (Thr69/71) in SCC-25 cells, with maximal inhibition observed in TGF-beta-1-pretreated cells^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

ELISA Assay^[1]

Cell Line:

Mouse RAW264.7 macrophages
Concentration:

1 nM-20 μM
Incubation Time:

2 h (pre-incubation); 30 min (anisomycin stimulation)
Result:

Inhibited anisomycin-induced MK2 phosphorylation with an IC₅₀ of 35.3 nM.

ELISA Assay^[1]

Cell Line:

Mouse peritoneal macrophages
Concentration:

1 nmol/L-20 μmol/L
Incubation Time:

0.5 h (pre-incubation); 2 h (LPS/IFN-γ stimulation)
Result:

Reduced TNF-α secretion with an IC₅₀ of 6.3 nmol/L.

Western Blot Analysis^[1]

Cell Line:

HeLa cells
Concentration:

9.8 nmol/L-10 μmol/L
Incubation Time:

1 h (pre-incubation); 45 min (anisomycin stimulation)
Result:

Inhibited phospho-Thr334-MK2 at 9.8 nmol/L. Caused complete ablation of phospho-Thr334-MK2 phosphorylation at 156 nmol/L. Showed no changes in phosphorylation of p38α MAPK, JNK, ERK1/2, c-Jun, ATF2, or c-Myc at concentrations ≤10 μmol/L.

ELISA Assay^[1]

Cell Line:

A549 non-small cell lung cancer cells
Concentration:

1 nmol/L-20 μmol/L
Incubation Time:

30 min (pre-incubation); 72 h (LPS stimulation)
Result:

Reduced LPS-induced CXCL8 secretion with an IC₅₀ of 144.9 nmol/L.

Apoptosis Analysis^[2]

Cell Line:

cisplatin-resistant head and neck squamous cell carcinoma (HNSCC) SCC-25 cells
Concentration:

1.6 μM
Incubation Time:

two 72 h treatment intervals (treatment from day 5 to day 11)
Result:

Induced Annexin positivity in 19.12% of cells. Induced 14.51% of cells in the sub-G1 (apoptotic) phase. Enhanced TGF-beta-1-induced Annexin positivity to 24.23%. Caused G2/S cell cycle arrest with increased cell population in the G2-M phase (9.77%) in TGF-beta-1-pretreated cells. Resulted in 7.88% of cells in the sub-G1 phase when combined with TGF-beta-1.

Western Blot Analysis^[2]

Cell Line:

cisplatin-resistant HNSCC SCC-25 cells
Concentration:

1.6 μM
Incubation Time:

two 72 h treatment intervals
Result:

Reduced phosphorylated ATF2 (Thr69/71) levels compared to control. Maximally reduced phosphorylated ATF2 (Thr69/71) levels when combined with TGF-beta-1, with a statistically significant decrease relative to TGF-beta-1 treatment alone.

Parmacokinetics

Species	Dose	Route	T_1/2
Mice^[1]	20 mg/kg	p.o.	2.8 h

In Vivo

Ralimetinib (0.1-30 mg/kg; p.o.; single dose) dose-dependently inhibits tumor phospho-MK2 in C57BL/6 mice bearing B16-F10 melanoma, with a TED₅₀ of 1.95 mg/kg and >40% target inhibition maintained for 4 to 8 hours after a single 10 mg/kg oral dose^[1].
Ralimetinib (20 mg/kg; p.o.; 3 times a day; continuous or intermittent schedule) administered at 20 mg/kg three times daily via continuous or intermittent oral schedules produces significant tumor growth delay in athymic nude mice bearing A549 non-small cell lung cancer xenografts^[1].
Ralimetinib (10 mg/kg; p.o.; 3 times a day; 4 days on/3 days off; 3 weeks) administered at 10 mg/kg three times daily on a 4 days on/3 days off oral schedule achieves 72% tumor growth inhibition in CD1 nu/nu mice bearing A-2780 ovarian cancer xenografts^[1].
Ralimetinib (14.7 mg/kg; p.o.; twice a day; continuous schedule) administered at 14.7 mg/kg twice daily via continuous oral schedule completely attenuates tumor growth in athymic nude mice bearing U-87MG glioma xenografts^[1].
Ralimetinib (p.o.) administered via oral schedule produces 60% tumor growth inhibition in athymic nude mice bearing MDA-MB-468 breast cancer xenografts^[1].
Ralimetinib (p.o.) administered via oral schedule produces 42% tumor growth inhibition in irradiated CB-17 SCID mice bearing OPM-2 multiple myeloma xenografts^[1].
Ralimetinib (30 mg/kg; p.o.; 3 times a day; 4 days on/3 days off; 14 consecutive days) administered at 30 mg/kg three times daily on a 4 days on/3 days off oral schedule reduces lung metastases by 57% in nude mice with B16-F10 melanoma tail vein metastases^[1].
Ralimetinib (10-30 mg/kg; p.o.; 3 times a day; 3 days on/3 days off; 3 weeks) administered at 10 mg/kg or 30 mg/kg three times daily on a 3 days on/3 days off oral schedule produces 50% to 51% tumor growth inhibition in female athymic nude mice with orthotopic intraperitoneal SK-OV-3 ovarian cancer xenografts^[1].
Ralimetinib (30 mg/kg; p.o.; 3 times a day; continuous; 3 weeks) administered at 30 mg/kg three times daily via continuous oral schedule produces a 44% decrease in tumor luminescence and 35% reduction in tumor weight in female athymic nude mice with orthotopic renal capsule 786-O renal carcinoma xenografts^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

C57BL/6 (implanted with 2 × 10⁶ B16-F10 melanoma cells)^[1]
Dosage:

0.1-30 mg/kg (single doses)
Administration:

p.o.; single dose
Result:

Inhibited tumor phospho-MK2 (p-Thr334) in a dose-dependent manner, with a TED50 = 1.95 mg/kg and TED70 = 11.17 mg/kg.
Maintained >40% inhibition of tumor phospho-MK2 for 4 to 8 hours (10 mg/kg dose).

Animal Model:

Athymic nude (implanted with 1 × 10⁷ A549 cells)^[1]
Dosage:

20 mg/kg
Administration:

p.o.; 3 times a day; continuous (days 4-38); intermittent (3 days on/3 days off, starting day 16)
Result:

Produced significant tumor growth delay compared with vehicle control.
Showed no significant difference in efficacy between continuous and intermittent schedules.

Animal Model:

CD1 nu/nu (implanted with 2 × 10⁶ A-2780 cells)^[1]
Dosage:

10 mg/kg
Administration:

p.o.; 3 times a day; 4 days on/3 days off; 3 weeks
Result:

Achieved 72% tumor growth inhibition on the last day of study treatment.

Animal Model:

Athymic nude (implanted with 5 × 10⁶ U-87MG cells)^[1]
Dosage:

14.7 mg/kg
Administration:

p.o.; twice a day; continuous (days 11-28)
Result:

Completely attenuated tumor growth during the treatment period.

Animal Model:

Nude (injected via tail vein with 50,000 B16-F10 melanoma cells 1 day before treatment)^[1]
Dosage:

10 mg/kg; 30 mg/kg
Administration:

p.o.; 3 times a day; 4 days on/3 days off; 14 consecutive days
Result:

Reduced the number of lung metastases by 57% at the 30 mg/kg dose.

Animal Model:

Female athymic nude (20-25 g; orthotopic implant of 2 × 10⁶ luciferase-labeled 786-O cells into renal capsule of left kidney)^[1]
Dosage:

30 mg/kg
Administration:

p.o.; 3 times a day; continuous; 3 weeks
Result:

Produced a 44% decrease in luminescence after 3 weeks.
Reduced average excised tumor weight by 35%.

Essai clinique

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

Chemical Information

CAS No. 862505-00-8
Appearance Powder
Masse moléculaire 420.53
Formule C₂₄H₂₉FN₆
Color White to off-white
SMILES

NC1=NC2=CC=C(C3=C(C4=CC=C(F)C=C4)N=C(C(C)(C)C)N3)N=C2N1CC(C)(C)C
Synonyms

LY2228820
Livraison

Room temperature in continental US; may vary elsewhere.

Stockage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Publications (17)

All Cell Proliferation/Viability AssayELISAWB

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Journal Impact Factor

Nat Commun

Inhibition of cytoplasmic EZH2 induces antitumor activity through stabilization of the DLC1 tumor suppressor protein. [Abstract]

2021 Dec 3;12(1):6941. PMID: 34862367
Sci Transl Med

PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells. [Abstract]

2018 Jul 18;10(450):eaaq1093. PMID: 30021885
Cell Death Dis

Quantitative analysis of phosphoproteome in necroptosis reveals a role of TRIM28 phosphorylation in promoting necroptosis-induced cytokine production. [Abstract]

2021 Oct 23;12(11):994. PMID: 34689152

Ralimetinib purchased from MedChemExpress. Usage Cited in: Cell Death Dis. 2021 Oct 23;12(11):994. [Abstract]

HT-29 cells were transfected with an expression vector of flag-tagged MLKL fused with two AP20187 (10 μM)-binding (FKBPv) domains. The cells were pretreated with indicated compounds (Ralimetinib dimesylate (LY2228820, 10 μM), et al.) for 4 h followed by treatment with AP20187 to induce MLKL oligomerization. Cell viability was determined by CellTiter-Glo after treatment with AP20187 for 2 h (Left). Cell lysates were separated by non-reducing SDS/PAGE and analyzed by western blotting using MLKL antibody (Right).
EBioMedicine

PP2AC Level Determines Differential Programming of p38-TSC-mTOR Signaling and Therapeutic Response to p38-Targeted Therapy in Colorectal Cancer. [Abstract]

2015 Nov 19;2(12):1944-56. PMID: 26844273

Ralimetinib purchased from MedChemExpress. Usage Cited in: EBioMedicine. 2015 Nov 19;2(12):1944-56. [Abstract]

CRC cells were treated with 4 μM Ralimetinib dimesylate (LY2228820), 10 μM BIRB796 or 10 μM SB202190 for 2 h and p38 and mTORC1 signaling was analyzed by immunoblot.
Oncogene

ULK1 promotes metastatic progression in experimental models of epithelial ovarian cancer. [Abstract]

2026 Mar 5. PMID: 41786876

Ralimetinib purchased from MedChemExpress. Usage Cited in: Oncogene. 2026 Mar 5. [Abstract]

Spheroids were cultured for 24 h before treating with either AKTi-1/2 (5 µM) or Ralimetinib dimesylate (15 µM) for 72 h before performing Trypan Blue Exclusion Assay. Treatment with AKTi-1/2 (AKT inhibitor) and Ralimetinib dimesylate (p38 inhibitor) resulted in significantly increased cell viability in OVCAR8-ULK1KO spheroids, while no differences were observed in HEYA8-ULK1KO spheroids.
Cell Rep

VEGFR2 inhibition potentiates STING-mediated antitumor immunity. [Abstract]

2026 Jun 18;45(7):117576. PMID: 42313565
Cell Rep

Pharmacological boosting of cGAS activation sensitizes chemotherapy by enhancing antitumor immunity. [Abstract]

2023 Mar 20;42(3):112275. PMID: 36943864
Commun Biol

Dickkopf1 fuels inflammatory cytokine responses. [Abstract]

2022 Dec 20;5(1):1391. PMID: 36539532
Glia

Activation of G protein-coupled receptor 30 protects neurons by regulating autophagy in astrocytes. [Abstract]

2020 Jan;68(1):27-43. PMID: 31429156
Mol Med Rep

MicroRNA‑22 alleviates inflammation in ischemic stroke via p38 MAPK pathways. [Abstract]

2019 Jul;20(1):735-744. PMID: 31115561

Ralimetinib purchased from MedChemExpress. Usage Cited in: Mol Med Rep. 2019 Jul;20(1):735-744. [Abstract]

p38 inhibitor Ralimetinib dimesylate (p38 i, 3 nM; 24 h) reduced the proinflammatory effects of Anti-22 in model in vitro. p-p38, NF-κB, COX-2 and iNOS protein expression was determined by western blotting and statistically analyzed.

Ralimetinib purchased from MedChemExpress. Usage Cited in: Mol Med Rep. 2019 Jul;20(1):735-744. [Abstract]

p38 inhibitor Ralimetinib dimesylate (p38 i, 3 nM; 24 h) reduced the proinflammatory effects of Anti-22 in the in vitro stroke model. TNF-α, IL-1β, IL-6, IL-18, MIP-2 and PGE2 expression was determined by ELISA.
Toxics

Co-Exposure of Microplastics and Avermectin at Environmental-Related Concentrations Caused Severe Heart Damage Through ROS-Mediated MAPK Signaling in Larval and Adult Zebrafish. [Abstract]

2025 Dec 25;14(1):24. PMID: 41600573
Med Oncol

P38MAPK targeting in pancreatic ductal adenocarcinoma: Promising interventional approach for breaking drug resistance and tumor control. [Abstract]

2026 Jun 3;43(7):191. PMID: 42234045
Eur J Immunol

Neutralization of IL-10 produced by B cells promotes protective immunity during persistent HCV infection in humanized mice. [Abstract]

2020 Sep;50(9):1350-1361. PMID: 32339264
Cell Biol Int

Lipopolysaccharide inhibits GPR120 expression in macrophages via Toll-like receptor 4 and p38 MAPK activation. [Abstract]

2020 Jan;44(1):89-97. PMID: 31322778
Mol Cell Biol

Kinase Inhibitor-Induced Cell-Type Specific Vacuole Formation in the Absence of Canonical ATG5-Dependent Autophagy Initiation Pathway. [Abstract]

2025;45(3):99-115. PMID: 39895059
Res Sq

2025 Apr 15.
bioRxiv

2023 Feb 8.

Solvant et solubilité

In Vitro:

DMSO : 100 mg/mL (237.80 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

2.3780 mL

11.8898 mL

23.7795 mL

5 mM

0.4756 mL

2.3780 mL

4.7559 mL

10 mM

0.2378 mL

1.1890 mL

2.3780 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Calculateur de molarité

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Calculateur de dilution

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

Concentration _(final) Concentration _(final)

Volume _(final) Volume _(final)

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 2.5 mg/mL (5.94 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 2

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (5.94 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

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mg/kg
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g
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μL
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
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The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Pureté et documentation

Select Batch:

Pureté: 99.98%

Assay: 99.98%

ee.: 99.98%

Fiche technique (293 KB)
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COA (2659 KB)
Elemental Analysis Report (2659 KB)
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Références

[1]. Campbell RM, et al. Characterization of LY2228820 dimesylate, a potent and selective inhibitor of p38 MAPK with antitumor activity. Mol Cancer Ther. 2014;13(2):364-374. [Content Brief]

[2]. Federspiel J, et al. p38 Mitogen-Activated Protein Kinase Inhibition of Mesenchymal Transdifferentiated Tumor Cells in Head and Neck Squamous Cell Carcinoma. Biomedicines. 2023;11(12):3301. Published 2023 Dec 13. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	2.3780 mL	11.8898 mL	23.7795 mL	59.4488 mL
	5 mM	0.4756 mL	2.3780 mL	4.7559 mL	11.8898 mL
	10 mM	0.2378 mL	1.1890 mL	2.3780 mL	5.9449 mL
	15 mM	0.1585 mL	0.7927 mL	1.5853 mL	3.9633 mL
	20 mM	0.1189 mL	0.5945 mL	1.1890 mL	2.9724 mL
	25 mM	0.0951 mL	0.4756 mL	0.9512 mL	2.3780 mL
	30 mM	0.0793 mL	0.3963 mL	0.7927 mL	1.9816 mL
	40 mM	0.0594 mL	0.2972 mL	0.5945 mL	1.4862 mL
	50 mM	0.0476 mL	0.2378 mL	0.4756 mL	1.1890 mL
	60 mM	0.0396 mL	0.1982 mL	0.3963 mL	0.9908 mL
	80 mM	0.0297 mL	0.1486 mL	0.2972 mL	0.7431 mL
	100 mM	0.0238 mL	0.1189 mL	0.2378 mL	0.5945 mL

Ralimetinib

17 Cited Publications

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Ralimetinib

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Publications Citing Use of MedChemExpress (MCE) Ralimetinib

Voir tous les produits spécifiques à Isoform p38 MAPK

Activité biologique

Chemical Information

Publications (17)

Solvant et solubilité

Pureté et documentation

Références

Help & FAQs

Complete Stock Solution Preparation Table

Ralimetinib Related Classifications

HY-13241A Related Classifications