Details
Stereochemistry | ACHIRAL |
Molecular Formula | C24H29FN6.2CH4O3S |
Molecular Weight | 612.737 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CS(O)(=O)=O.CS(O)(=O)=O.CC(C)(C)CN1C(N)=NC2=CC=C(N=C12)C3=C(NC(=N3)C(C)(C)C)C4=CC=C(F)C=C4
InChI
InChIKey=NARMJPIBAXVUIE-UHFFFAOYSA-N
InChI=1S/C24H29FN6.2CH4O3S/c1-23(2,3)13-31-20-17(28-22(31)26)12-11-16(27-20)19-18(14-7-9-15(25)10-8-14)29-21(30-19)24(4,5)6;2*1-5(2,3)4/h7-12H,13H2,1-6H3,(H2,26,28)(H,29,30);2*1H3,(H,2,3,4)
DescriptionSources: http://adisinsight.springer.com/drugs/800034528Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/24356814
Sources: http://adisinsight.springer.com/drugs/800034528
Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/24356814
Ralimetinib (LY2228820), a trisubstituted imidazole derivative, is a potent and selective, ATP-competitive inhibitor of the α- and β-isoforms of p38 mitogen-activated protein kinase. LY2228820 produced significant tumor growth delay in multiple in vivo cancer models (melanoma, non-small cell lung cancer, ovarian, glioma, myeloma, breast). Eli Lilly is developing ralimetinib for the treatment of cancer.
Originator
Sources: http://adisinsight.springer.com/drugs/800034528
Curator's Comment: # Eli Lilly
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL260 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24356814 |
5.3 nM [IC50] | ||
Target ID: CHEMBL3961 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24356814 |
3.2 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1400 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26581242 |
300 mg 2 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RALIMETINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
2230 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26581242 |
420 mg 2 times / day steady-state, oral dose: 420 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RALIMETINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
3060 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26581242 |
560 mg 2 times / day steady-state, oral dose: 560 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RALIMETINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
574 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26581242 |
160 mg 2 times / day steady-state, oral dose: 160 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RALIMETINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
963 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26581242 |
200 mg 2 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RALIMETINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
17900 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26581242 |
300 mg 2 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RALIMETINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
26200 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26581242 |
420 mg 2 times / day steady-state, oral dose: 420 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RALIMETINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
40500 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26581242 |
560 mg 2 times / day steady-state, oral dose: 560 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RALIMETINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
7490 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26581242 |
160 mg 2 times / day steady-state, oral dose: 160 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RALIMETINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
92.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26581242 |
300 mg 2 times / day steady-state, oral dose: 300 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RALIMETINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
77.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26581242 |
420 mg 2 times / day steady-state, oral dose: 420 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RALIMETINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
193 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26581242 |
560 mg 2 times / day steady-state, oral dose: 560 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RALIMETINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
|
86.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26581242 |
160 mg 2 times / day steady-state, oral dose: 160 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
RALIMETINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
PubMed
Title | Date | PubMed |
---|---|---|
Imidazolyl benzimidazoles and imidazo[4,5-b]pyridines as potent p38alpha MAP kinase inhibitors with excellent in vivo antiinflammatory properties. | 2008 Jan 1 |
|
LY2228820 dimesylate, a selective inhibitor of p38 mitogen-activated protein kinase, reduces angiogenic endothelial cord formation in vitro and in vivo. | 2013 Mar 1 |
|
Characterization of LY2228820 dimesylate, a potent and selective inhibitor of p38 MAPK with antitumor activity. | 2014 Feb |
|
P38 regulates the Wnt inhibitor Dickkopf-1 in breast cancer. | 2015 Oct 30 |
|
p38 MAPK regulates the Wnt inhibitor Dickkopf-1 in osteotropic prostate cancer cells. | 2016 Feb 25 |
|
A First-in-Human Phase I Study of the Oral p38 MAPK Inhibitor, Ralimetinib (LY2228820 Dimesylate), in Patients with Advanced Cancer. | 2016 Mar 1 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26581242
The recommended phase II dose of Ralimetinib in patients with advanced cancer was 300 mg every 12 hours as monotherapy or in combination with tamoxifen.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24356814
In cell-based assays, Ralimetinib (LY2228820) potently and selectively inhibited phosphorylation of MK2 (Thr334) in anisomycin-stimulated HeLa cells (at 9.8 nmol/L by Western blot analysis) and anisomycin-induced mouse RAW264.7 macrophages (IC(50) = 35.3 nmol/L) with no changes in phosphorylation of p38α MAPK, JNK, ERK1/2, c-Jun, ATF2, or c-Myc ≤ 10 μmol/L. LY2228820 also reduced TNF-α secretion by lipopolysaccharide/IFN-γ-stimulated macrophages (IC(50) = 6.3 nmol/L).
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NCI_THESAURUS |
C61074
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NCI_THESAURUS |
C129825
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300000044459
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QUW7B71FO9
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1138756-70-3
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862505-01-9
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C105853
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CHEMBL2364626
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ZZ-84
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DBSALT002074
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11570805
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DTXSID60235457
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ACTIVE MOIETY
SUBSTANCE RECORD