SOTULETINIB

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 Search

SMILES

CNC(=O)C1=NC=CC(OC2=CC=C3N=C(N[C@@H]4CCCC[C@H]4O)SC3=C2)=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	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24056773
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

Targets

Primary Target	Pharmacology	Condition	Potency
Macrophage colony stimulating factor receptor 24 Target ID: CHEMBL1844 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25180976	Inhibitor 8297		1.2 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Glioblastoma 65 Sources: https://clinicaltrials.gov/ct2/show/NCT02829723	Primary	Phase II 1132	Unknown Approved Use Unknown
Pancreatic cancer 97 Sources: https://clinicaltrials.gov/ct2/show/NCT02829723	Primary	Phase II 1132	Unknown Approved Use Unknown
Triple-negative breast cancer 12 Sources: https://clinicaltrials.gov/ct2/show/NCT02829723	Primary	Phase II 1132	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse 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: https://cancerres.aacrjournals.org/content/80/16_Supplement/CT171	unhealthy, ADULT Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://cancerres.aacrjournals.org/content/80/16_Supplement/CT171	Sources: https://cancerres.aacrjournals.org/content/80/16_Supplement/CT171

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY103162	https://www.001chemical.com/chem/search?q=DY103162
1PlusChem LLC	1P0036PI	https://www.1pchem.com/search?query=1P0036PI
AChemBlock	K12024	http://www.achemblock.com/catalogsearch/result/?q=K12024
AK Scientific	3193AH	https://aksci.com/item_detail.php?cat=3193AH
AK Scientific	SYN1197	https://aksci.com/item_detail.php?cat=SYN1197
Ambeed	A156169	http://www.ambeed.com/search/Search.html?keyword=A156169
Angene	AGN-PC-0WAKVY	http://www.angenechemical.com/productshow/AGN-PC-0WAKVY.html
ApexBio Technology	B4899	https://www.apexbt.com/catalogsearch/result/?q=B4899
AstaTech	I10001	http://astatechinc.com/CPSResult.php?CRNO=I10001
Cayman Chemical	19626	http://www.caymanchem.com/app/template/Product.vm/catalog/19626
Chem Scene	CS-3971	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3971
ChemShuttle	106245	https://www.chemshuttle.com/catalogsearch/result/?q=106245
Fluorochem	501110	http://www.fluorochem.co.uk/Products/Product?code=501110
KeyOrganics	AS-16330	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16330
Lab Network	LN01342418	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01342418
Lab Seeker	SC-85415	http://www.labseeker.com/search.php?keywords=SC-85415&category=0
Matrix Scientific	120901	http://www.matrixscientific.com/120901.html
MedChem Express	HY-12768	https://www.medchemexpress.com/search.html?q=HY-12768&ft=&fa=&fp=
MolPort	MolPort-035-941-523	https://www.molport.com/shop/molecule-link/MolPort-035-941-523
Molcore	MC103162	http://www.molcore.com/CatMC103162.html
Molnova	M16814	https://www.molnova.com/en/serch-list.html?keywords=M16814
MuseChem	I005655	https://www.musechem.com/product/I005655.html
Selleck Chemicals	S7725	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7725
ShangHai Biochempartner	BCP001377	http://www.biochempartner.com/search_BCP001377
TargetMol	T6119	https://www.targetmol.com/search?keyword=T6119
Toronto Research Chemicals	B595835	https://www.trc-canada.com/product-detail/?CatNum=B595835
eMolecules	275105390	https://orderbb.emolecules.com/search/#?query=275105390
eMolecules	301197931	https://orderbb.emolecules.com/search/#?query=301197931
eMolecules	49829323	https://orderbb.emolecules.com/search/#?query=49829323
eNovation Chemicals	D501844	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D501844&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-1122339961	https://mcule.com/MCULE-1122339961/
mcule	MCULE-6022993488	https://mcule.com/MCULE-6022993488/

PubMed

Title	Date	PubMed
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	24498562
Phenotypic and metabolic investigation of a CSF-1R kinase receptor inhibitor (BLZ945) and its pharmacologically active metabolite.	2015 Feb	25180976

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 `Sat Dec 16 11:05:55 GMT 2023` Edited by `admin` on `Sat Dec 16 11:05:55 GMT 2023`
Record UNII	7W3V82OQ0P
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SOTULETINIB

Official Name

English

2-PYRIDINECARBOXAMIDE, 4-((2-(((1R,2R)-2-HYDROXYCYCLOHEXYL)AMINO)-6-BENZOTHIAZOLYL)OXY)-N-METHYL-

Systematic Name

English

sotuletinib [INN]

Common Name

English

BLZ-945

Common Name

English

CSF-1R INHIBITOR BLZ945

Common Name

English

BLZ 945 [WHO-DD]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

897222