Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C20H22N4O3S.2ClH |
| Molecular Weight | 471.401 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.Cl.CNC(=O)C1=NC=CC(OC2=CC=C3N=C(N[C@@H]4CCCC[C@H]4O)SC3=C2)=C1
InChI
InChIKey=ZIHWHYXECXSBNA-LVVRIOTCSA-N
InChI=1S/C20H22N4O3S.2ClH/c1-21-19(26)16-10-13(8-9-22-16)27-12-6-7-15-18(11-12)28-20(24-15)23-14-4-2-3-5-17(14)25;;/h6-11,14,17,25H,2-5H2,1H3,(H,21,26)(H,23,24);2*1H/t14-,17-;;/m1../s1
| Molecular Formula | C20H22N4O3S |
| Molecular Weight | 398.479 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
| Molecular Formula | ClH |
| Molecular Weight | 36.461 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionCurator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/24056773 | https://www.ncbi.nlm.nih.gov/pubmed/21653914
Curator's Comment: description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/24056773 | https://www.ncbi.nlm.nih.gov/pubmed/21653914
BLZ 945, an orally active antagonist of the colony-stimulating factor1
receptor (CSF1R), is being developed by Novartis and Celgene Corporation for the treatment of advanced solid tumors and tumor-induced osteolytic lesions in bone and skeletal-related events. Phase I/II development for solid tumors is underway in the US, Italy, Spain, and Singapore. Preclinical trials were ongoing for tumor-induced osteolysis in Europe and the US. However, no recent reports of development had been identified for this indication.
CNS Activity
Originator
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| Investigation of correlation among safety biomarkers in serum, histopathological examination, and toxicogenomics. | 2011 May |
|
| CSF1R inhibition delays cervical and mammary tumor growth in murine models by attenuating the turnover of tumor-associated macrophages and enhancing infiltration by CD8(+) T cells. | 2013 Dec 1 |
|
| Phenotypic and metabolic investigation of a CSF-1R kinase receptor inhibitor (BLZ945) and its pharmacologically active metabolite. | 2015 Feb |
Sample Use Guides
Mice received 200 mg per kg body weight BLZ945 or vehicle (20% Captisol) by oral gavage once daily. BLZ945 was formulated in 20% Captisol at a concentration of 12.5 mg ml−1. Mice were dosed daily for 15 d, and tumor growth was monitored every 5 d by bioluminescence imaging.
Route of Administration:
Oral
Treatment of wild-type (WT) bone marrow–derived macrophages (BMDMs) with BLZ945 inhibited CSF-1–dependent prolifera¬tion (half-maximum effective concentration (EC50) = 67 nM) and decreased CSF-1R phosphorylation, similarly to blockade with CSF-1R–specific antibody. Primary bone marrow-derived macrophages (BMDMs) were cultured in the absence of CSF-1 for 12 hours prior to stimulation, followed by CSF-1 addition for the indicated time points (1.5, 3 and 5 minutes).
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 14:34:42 UTC 2023
by
admin
on
Sat Dec 16 14:34:42 UTC 2023
|
| Record UNII |
QJE0UTG9TS
|
| Record Status |
Validated (UNII)
|
| Record Version |
|
-
Download
| Name | Type | Language | ||
|---|---|---|---|---|
|
Common Name | English | ||
|
Code | English | ||
|
Systematic Name | English | ||
|
Code | English |
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
|
C183175
Created by
admin on Sat Dec 16 14:34:42 UTC 2023 , Edited by admin on Sat Dec 16 14:34:42 UTC 2023
|
PRIMARY | |||
|
2222138-40-9
Created by
admin on Sat Dec 16 14:34:42 UTC 2023 , Edited by admin on Sat Dec 16 14:34:42 UTC 2023
|
PRIMARY | |||
|
138455086
Created by
admin on Sat Dec 16 14:34:42 UTC 2023 , Edited by admin on Sat Dec 16 14:34:42 UTC 2023
|
PRIMARY | |||
|
QJE0UTG9TS
Created by
admin on Sat Dec 16 14:34:42 UTC 2023 , Edited by admin on Sat Dec 16 14:34:42 UTC 2023
|
PRIMARY |
| Related Record | Type | Details | ||
|---|---|---|---|---|
|
ACTIVATOR -> TARGET |
