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
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
| 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 |
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/21900693http://www.lillyoncologypipeline.com/molecule/fgfr-inhibitor/overviewCurator'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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21900693http://www.lillyoncologypipeline.com/molecule/fgfr-inhibitor/overview
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.
Originator
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21900693http://adisinsight.springer.com/drugs/800032325
Curator's Comment: # Eli Lilly
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL3650 |
2.8 nM [IC50] | ||
Target ID: CHEMBL4142 |
2.6 nM [IC50] | ||
Target ID: CHEMBL2742 |
6.4 nM [IC50] | ||
Target ID: CHEMBL3973 |
6.0 nM [IC50] | ||
Target ID: CHEMBL279 |
7.0 nM [IC50] | ||
Target ID: CHEMBL3839 |
6.0 nM [IC50] | ||
Target ID: CHEMBL4066 |
6.4 nM [IC50] | ||
Target ID: CHEMBL3650 |
2.8 nM [IC50] | ||
Target ID: CHEMBL4142 |
2.6 nM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
|||
| Primary | Unknown Approved UseUnknown |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| 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 |
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
Edited
Sat Dec 16 10:03:23 GMT 2023
by
admin
on
Sat Dec 16 10:03:23 GMT 2023
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| Record UNII |
E9M363811V
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| Record Status |
Validated (UNII)
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| Record Version |
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ACTIVE MOIETY |
