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Details

Stereochemistry ABSOLUTE
Molecular Formula C20H22N4O3S
Molecular Weight 398.479
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BLZ-945

SMILES

CNC(=O)C1=NC=CC(OC2=CC3=C(C=C2)N=C(N[C@@H]4CCCC[C@H]4O)S3)=C1

InChI

InChIKey=ADZBMFGQQWPHMJ-RHSMWYFYSA-N
InChI=1S/C20H22N4O3S/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)/t14-,17-/m1/s1

HIDE SMILES / InChI

Molecular Formula C20H22N4O3S
Molecular Weight 398.479
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

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

PubMed

TitleDatePubMed
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
Patents

Sample Use Guides

In Vivo Use Guide
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
In Vitro Use Guide
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 Mon Oct 21 21:39:24 UTC 2019
Edited
by admin
on Mon Oct 21 21:39:24 UTC 2019
Record UNII
7W3V82OQ0P
Record Status Validated (UNII)
Record Version
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Name Type Language
BLZ-945
Common Name English
BLZ 945 [WHO-DD]
Common Name English
2-PYRIDINECARBOXAMIDE, 4-((2-(((1R,2R)-2-HYDROXYCYCLOHEXYL)AMINO)-6-BENZOTHIAZOLYL)OXY)-N-METHYL-
Systematic Name English
CSF-1R INHIBITOR BLZ945
Common Name English
Code System Code Type Description
CAS
953769-46-5
Created by admin on Mon Oct 21 21:39:24 UTC 2019 , Edited by admin on Mon Oct 21 21:39:24 UTC 2019
PRIMARY
PUBCHEM
46184986
Created by admin on Mon Oct 21 21:39:24 UTC 2019 , Edited by admin on Mon Oct 21 21:39:24 UTC 2019
PRIMARY
NCI_THESAURUS
C129653
Created by admin on Mon Oct 21 21:39:24 UTC 2019 , Edited by admin on Mon Oct 21 21:39:24 UTC 2019
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
TARGET -> ACTIVATOR
Related Record Type Details
ACTIVE MOIETY