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Details

Stereochemistry ACHIRAL
Molecular Formula C24H29FN6
Molecular Weight 420.5257
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of RALIMETINIB

SMILES

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=XPPBBJCBDOEXDN-UHFFFAOYSA-N
InChI=1S/C24H29FN6/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/h7-12H,13H2,1-6H3,(H2,26,28)(H,29,30)

HIDE SMILES / InChI

Molecular Formula C24H29FN6
Molecular Weight 420.5257
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
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

Curator's Comment: # Eli Lilly

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
5.3 nM [IC50]
3.2 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1400 ng/mL
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
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
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
17900 ng × h/mL
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
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
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
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

T1/2

ValueDoseCo-administeredAnalytePopulation
92.6 h
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
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
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
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
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Imidazolyl benzimidazoles and imidazo[4,5-b]pyridines as potent p38alpha MAP kinase inhibitors with excellent in vivo antiinflammatory properties.
2008 Jan 1
Characterization of LY2228820 dimesylate, a potent and selective inhibitor of p38 MAPK with antitumor activity.
2014 Feb
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

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 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).
Substance Class Chemical
Created
by admin
on Sat Dec 16 17:49:55 UTC 2023
Edited
by admin
on Sat Dec 16 17:49:55 UTC 2023
Record UNII
73I34XW4HD
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
RALIMETINIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
LSN-2322600 FREE BASE
Code English
ralimetinib [INN]
Common Name English
3H-IMIDAZO(4,5-B)PYRIDIN-2-AMINE, 5-(2-(1,1-DIMETHYLETHYL)-4-(4-FLUOROPHENYL)-1H-IMIDAZOL-5-YL)-3-(2,2-DIMETHYLPROPYL)-
Systematic Name English
LY-2228820
Code English
LSN2322600 FREE BASE
Code English
RALIMETINIB [USAN]
Common Name English
Ralimetinib [WHO-DD]
Common Name English
LY2228820
Code English
5-(2-TERT-BUTYL-5-(4-FLUORO-PHENYL)-1H-IMIDAZOL-4-YL)-3-(2,2-DIMETHYL-PROPYL)-3H-IMIDAZO(4,5-B)PYRIDIN-2-YLAMINE
Systematic Name English
5-(2-(tert-Butyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)-3-(2,2-dimethylpropyl)-3H-imidazo[4,5-b]pyridin-2-amine
Systematic Name English
Classification Tree Code System Code
NCI_THESAURUS C61074
Created by admin on Sat Dec 16 17:49:56 UTC 2023 , Edited by admin on Sat Dec 16 17:49:56 UTC 2023
Code System Code Type Description
CAS
862505-00-8
Created by admin on Sat Dec 16 17:49:56 UTC 2023 , Edited by admin on Sat Dec 16 17:49:56 UTC 2023
PRIMARY
USAN
ZZ-83
Created by admin on Sat Dec 16 17:49:56 UTC 2023 , Edited by admin on Sat Dec 16 17:49:56 UTC 2023
PRIMARY
INN
9753
Created by admin on Sat Dec 16 17:49:56 UTC 2023 , Edited by admin on Sat Dec 16 17:49:56 UTC 2023
PRIMARY
ChEMBL
CHEMBL2364626
Created by admin on Sat Dec 16 17:49:56 UTC 2023 , Edited by admin on Sat Dec 16 17:49:56 UTC 2023
PRIMARY
EPA CompTox
DTXSID00235456
Created by admin on Sat Dec 16 17:49:56 UTC 2023 , Edited by admin on Sat Dec 16 17:49:56 UTC 2023
PRIMARY
FDA UNII
73I34XW4HD
Created by admin on Sat Dec 16 17:49:56 UTC 2023 , Edited by admin on Sat Dec 16 17:49:56 UTC 2023
PRIMARY
EVMPD
SUB180754
Created by admin on Sat Dec 16 17:49:56 UTC 2023 , Edited by admin on Sat Dec 16 17:49:56 UTC 2023
PRIMARY
DRUG BANK
DB11787
Created by admin on Sat Dec 16 17:49:56 UTC 2023 , Edited by admin on Sat Dec 16 17:49:56 UTC 2023
PRIMARY
SMS_ID
100000166568
Created by admin on Sat Dec 16 17:49:56 UTC 2023 , Edited by admin on Sat Dec 16 17:49:56 UTC 2023
PRIMARY
NCI_THESAURUS
C143046
Created by admin on Sat Dec 16 17:49:56 UTC 2023 , Edited by admin on Sat Dec 16 17:49:56 UTC 2023
PRIMARY
PUBCHEM
11539025
Created by admin on Sat Dec 16 17:49:56 UTC 2023 , Edited by admin on Sat Dec 16 17:49:56 UTC 2023
PRIMARY
WIKIPEDIA
Ralimetinib
Created by admin on Sat Dec 16 17:49:56 UTC 2023 , Edited by admin on Sat Dec 16 17:49:56 UTC 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR