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Details

Stereochemistry ABSOLUTE
Molecular Formula C21H19Cl2N5O2
Molecular Weight 444.314
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of LY-2874455

SMILES

C[C@@H](OC1=CC2=C(NN=C2\C=C\C3=CN(CCO)N=C3)C=C1)C4=C(Cl)C=NC=C4Cl

InChI

InChIKey=GKJCVYLDJWTWQU-CXLRFSCWSA-N
InChI=1S/C21H19Cl2N5O2/c1-13(21-17(22)10-24-11-18(21)23)30-15-3-5-20-16(8-15)19(26-27-20)4-2-14-9-25-28(12-14)6-7-29/h2-5,8-13,29H,6-7H2,1H3,(H,26,27)/b4-2+/t13-/m1/s1

HIDE SMILES / InChI
Molecular Formula C21H19Cl2N5O2
Molecular Weight 444.314
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 1
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/27618313 | https://www.ncbi.nlm.nih.gov/pubmed/27245147

LY2874455 is a pan-FGFR inhibitor that binds to the ATP-binding pocket of FGFR4 in a unique, chair-like conformation through a multitude of interactions. LY2874455 exhibits a potential clinical use for treating various forms of human malignancies.

Originator

Approval Year

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8504
 2.8 nM [IC50]
Inhibitor
8504
 2.6 nM [IC50]
Inhibitor
8504
 6.4 nM [IC50]
Inhibitor
8504
 6.0 nM [IC50]
Inhibitor
8504
 7.0 nM [IC50]
Inhibitor
8504
 6.0 nM [IC50]
Inhibitor
8504
 6.4 nM [IC50]
Inhibitor
8504
 2.8 nM [IC50]
Inhibitor
8504
 2.6 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1147
Unknown

Approved Use

Unknown
Primary
Phase I
438
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
59.9 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/28589492/
36 mg single, oral
dose: 36 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LY-2874455 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
6.25 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/28589492/
2 mg single, oral
dose: 2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LY-2874455 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
29.9 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/28589492/
32 mg single, oral
dose: 32 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LY-2874455 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
35.5 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/28589492/
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LY-2874455 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
107 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/28589492/
48 mg single, oral
dose: 48 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LY-2874455 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
38.4 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/28589492/
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LY-2874455 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
29.9 ng/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/28589492
16 mg 2 times / day multiple, oral
dose: 16 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LY-2874455 blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
91.9 ng/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/28589492
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LY-2874455 blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
325 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/28589492/
36 mg single, oral
dose: 36 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LY-2874455 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
32.7 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/28589492/
2 mg single, oral
dose: 2 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LY-2874455 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
171 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/28589492/
32 mg single, oral
dose: 32 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LY-2874455 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
140 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/28589492/
20 mg single, oral
dose: 20 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LY-2874455 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
532 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/28589492/
48 mg single, oral
dose: 48 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LY-2874455 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
224 pg × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/28589492/
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LY-2874455 plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
171 ng × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/28589492
16 mg 2 times / day multiple, oral
dose: 16 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LY-2874455 blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
380 ng × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/28589492
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LY-2874455 blood
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
PubMed

PubMed

TitleDatePubMed
Crystal Structure of the FGFR4/LY2874455 Complex Reveals Insights into the Pan-FGFR Selectivity of LY2874455.
2016
A novel, selective inhibitor of fibroblast growth factor receptors that shows a potent broad spectrum of antitumor activity in several tumor xenograft models.
2011-11
Patents

Patents

08268869
1
08530665
1
20100286209
1
JP2013538875A
1
WO2014113729A2
1

Sample Use Guides

In Vivo Use Guide
Curator's Comment: The 16 mg BID dose was selected for the starting dose. DOI: 10.1158/1538-7445.AM2014-CT215
2, 4, 10 mg once daily for a minimum of 28 day cycle or 8 mg, 10 to 12 mg, 12 to 18 mg, 14 to 28 mg, 18 to 42 mg, 22 to 64 mg, 28 to 96 mg, 36 to 100 mg administered twice daily for a minimum of 28 day cycle.
Route of Administration: Oral
In Vitro Use Guide
LY2874455 potently inhibited the Erk phosphorylation induced by FGF2 and FGF9 in HUVECs and RT-112 cell lines in a dose-dependent manner, with average IC50 values of 0.3 to 0.8 nmol/L.
Substance Class Chemical
Created
by admin
on Mon Mar 31 22:59:48 GMT 2025
Edited
by admin
on Mon Mar 31 22:59:48 GMT 2025
Record UNII
E9M363811V
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LY-2874455
Common Name English
LY2874455
Preferred Name English
1H-PYRAZOLE-1-ETHANOL, 4-((1E)-2-(5-((1R)-1-(3,5-DICHLORO-4-PYRIDINYL)ETHOXY)-1H-INDAZOL-3-YL)ETHENYL)-
Systematic Name English
Code System Code Type Description
CAS
1254473-64-7
Created by admin on Mon Mar 31 22:59:48 GMT 2025 , Edited by admin on Mon Mar 31 22:59:48 GMT 2025
PRIMARY
SMS_ID
100000177753
Created by admin on Mon Mar 31 22:59:48 GMT 2025 , Edited by admin on Mon Mar 31 22:59:48 GMT 2025
PRIMARY
DRUG BANK
DB13022
Created by admin on Mon Mar 31 22:59:48 GMT 2025 , Edited by admin on Mon Mar 31 22:59:48 GMT 2025
PRIMARY
NCI_THESAURUS
C139004
Created by admin on Mon Mar 31 22:59:48 GMT 2025 , Edited by admin on Mon Mar 31 22:59:48 GMT 2025
PRIMARY
PUBCHEM
46944259
Created by admin on Mon Mar 31 22:59:48 GMT 2025 , Edited by admin on Mon Mar 31 22:59:48 GMT 2025
PRIMARY
EPA CompTox
DTXSID20154776
Created by admin on Mon Mar 31 22:59:48 GMT 2025 , Edited by admin on Mon Mar 31 22:59:48 GMT 2025
PRIMARY
ChEMBL
CHEMBL3545264
Created by admin on Mon Mar 31 22:59:48 GMT 2025 , Edited by admin on Mon Mar 31 22:59:48 GMT 2025
PRIMARY
FDA UNII
E9M363811V
Created by admin on Mon Mar 31 22:59:48 GMT 2025 , Edited by admin on Mon Mar 31 22:59:48 GMT 2025
PRIMARY
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Related Record Type Details
Structure of LY-2874455
ACTIVE MOIETY
NIH
NCATS
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