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Details

Stereochemistry ABSOLUTE
Molecular Formula C20H22N4O3S
Molecular Weight 398.4805
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BLZ-945

SMILES

CNC(=O)c1cc(ccn1)Oc2ccc3c(c2)sc(=N[C@]4([H])CCCC[C@@]4([H])O)[nH]3

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 398.4805
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
1.2 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
1200 mg 1 times / day multiple, oral
RP2D
Dose: 1200 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1200 mg, 1 times / day
Sources:
unhealthy, ADULT
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
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
Patents

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 Sat Jun 26 16:35:49 UTC 2021
Edited
by admin
on Sat Jun 26 16:35:49 UTC 2021
Record UNII
7W3V82OQ0P
Record Status Validated (UNII)
Record Version
  • Download
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
FDA UNII
7W3V82OQ0P
Created by admin on Sat Jun 26 16:35:49 UTC 2021 , Edited by admin on Sat Jun 26 16:35:49 UTC 2021
PRIMARY
CAS
953769-46-5
Created by admin on Sat Jun 26 16:35:49 UTC 2021 , Edited by admin on Sat Jun 26 16:35:49 UTC 2021
PRIMARY
PUBCHEM
46184986
Created by admin on Sat Jun 26 16:35:49 UTC 2021 , Edited by admin on Sat Jun 26 16:35:49 UTC 2021
PRIMARY
NCI_THESAURUS
C129653
Created by admin on Sat Jun 26 16:35:49 UTC 2021 , Edited by admin on Sat Jun 26 16:35:49 UTC 2021
PRIMARY NCIT
Related Record Type Details
TARGET -> INHIBITOR
TARGET -> ACTIVATOR
Related Record Type Details
ACTIVE MOIETY