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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:: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800032325 | https://www.ncbi.nlm.nih.gov/pubmed/21900693 | https://www.ncbi.nlm.nih.gov/pubmed/27245147 | DOI: 10.1158/1538-7445.AM2016-CT058

LY2874455 is reversible FGFR inhibitors that occupy the ATP-binding pocket in the kinase domain. According to Eli Lilly's pipeline LY 2874455 is in phase II trial in patients with advanced cancer. The most common drug-related adverse events included: hyperphosphatemia, diarrhea, anorexia and fatigue.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
35.5 ng/mL
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
29.9 ng/mL
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
107 ng/mL
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
6.25 ng/mL
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
38.4 ng/mL
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
59.9 ng/mL
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
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
140 ng × h/mL
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
171 ng × h/mL
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
532 ng × h/mL
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
32.7 ng × h/mL
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
224 pg × h/mL
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
325 ng × h/mL
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
PubMed

PubMed

TitleDatePubMed
Patents

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
Female CD1 nu/nu mice with Tumor xenograft was used to test the efficacy of LY2874455. The animals were orally dosed with approximately 1 mg/kg (TED50) or 3 mg/kg (TED90) of LY2874455 in 10% Acacia once (every day) or twice a day. LY2874455 exhibited a rapid, robust, dose-dependent inhibition of tumor growth, especially when dosed at 3 mg/kg twice a day.
Route of Administration: Oral
After overnight growth, RT-112 cells (DSMZ) were washed, incubated in RPMI 16409 containing 20 mg/mL bovine serum albumin (BSA) at 370C for 3 hours, and treated with LY2874455 (0.1nM-1mkM) at 37OC for 1 hour followed by the addition of FGF9 (500 ng/mL; R&D Systems) for 20 minutes.
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
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