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Details

Stereochemistry ABSOLUTE
Molecular Formula C21H19Cl2N5O2
Molecular Weight 444.3145
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of LY-2874455

SMILES

C[C@]([H])(c1c(cncc1Cl)Cl)Oc2ccc3c(c2)c(/C(/[H])=C(\[H])/c4cnn(CCO)c4)[nH]n3

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 444.3145
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 1
Optical Activity UNSPECIFIED

Description
Curator's Comment:: 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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
2.79999999999999982 nM [IC50]
2.60000000000000009 nM [IC50]
6.40000000000000036 nM [IC50]
6 nM [IC50]
7 nM [IC50]
6 nM [IC50]
6.40000000000000036 nM [IC50]
2.79999999999999982 nM [IC50]
2.60000000000000009 nM [IC50]
Conditions
PubMed

PubMed

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

Sample Use Guides

In Vivo Use Guide
Curator's Comment:: The 16 mg BID dose was selected for the starting dose.
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
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 Sat Jun 26 12:42:01 UTC 2021
Edited
by admin
on Sat Jun 26 12:42:01 UTC 2021
Record UNII
E9M363811V
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LY-2874455
Common 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
LY2874455
Code English
Code System Code Type Description
CAS
1254473-64-7
Created by admin on Sat Jun 26 12:42:01 UTC 2021 , Edited by admin on Sat Jun 26 12:42:01 UTC 2021
PRIMARY
DRUG BANK
DB13022
Created by admin on Sat Jun 26 12:42:01 UTC 2021 , Edited by admin on Sat Jun 26 12:42:01 UTC 2021
PRIMARY
PUBCHEM
46944259
Created by admin on Sat Jun 26 12:42:01 UTC 2021 , Edited by admin on Sat Jun 26 12:42:01 UTC 2021
PRIMARY
ChEMBL
CHEMBL3545264
Created by admin on Sat Jun 26 12:42:01 UTC 2021 , Edited by admin on Sat Jun 26 12:42:01 UTC 2021
PRIMARY
FDA UNII
E9M363811V
Created by admin on Sat Jun 26 12:42:01 UTC 2021 , Edited by admin on Sat Jun 26 12:42:01 UTC 2021
PRIMARY
EPA CompTox
1254473-64-7
Created by admin on Sat Jun 26 12:42:01 UTC 2021 , Edited by admin on Sat Jun 26 12:42:01 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
IC50
TARGET -> INHIBITOR
IC50
TARGET -> INHIBITOR
IC50
TARGET -> INHIBITOR
IC50
Related Record Type Details
ACTIVE MOIETY