REBASTINIB

Details

Stereochemistry	ACHIRAL
Molecular Formula	C30H28FN7O3
Molecular Weight	553.5868
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CNC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=NN3C4=CC=C5N=CC=CC5=C4)C(C)(C)C)C(F)=C2)=C1

InChI

InChIKey=WVXNSAVVKYZVOE-UHFFFAOYSA-N

InChI=1S/C30H28FN7O3/c1-30(2,3)26-17-27(38(37-26)19-7-9-23-18(14-19)6-5-12-33-23)36-29(40)35-24-10-8-20(15-22(24)31)41-21-11-13-34-25(16-21)28(39)32-4/h5-17H,1-4H3,(H,32,39)(H2,35,36,40)

HIDE SMILES / InChI

Description
Sources: https://www.deciphera.com/deciphera-pharmaceuticals-presents-preclinical-data-on-rebastinib-and-dcc-3014-at-aacr-tumor-microenvironment-conference/
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/21481795

Rebastinib (DCC-20) is a TIE2 kinase inhibitor currently in Phase 1 clinical development to treat breast cancer and Chronic Myeloid Leukemia. Rebastinib potently inhibited TIE2 kinase in cellular assays and blocked primary tumor growth by 75% as a single agent and by 90% in combination with the standard chemotherapeutic agent paclitaxel. Furthermore, rebastinib therapy significantly reduced the presence of tumor-promoting macrophages in tumor biopsies by 80%. This blockade of tumor macrophages correlated with inhibition of breast cancer lung metastases.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tyrosine-protein kinase ABL 29 Target ID: CHEMBL1862 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21481795	Inhibitor 8297		2.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Breast cancer 434 Sources: https://clinicaltrials.gov/ct2/show/NCT02824575	Primary		Phase I 428	Unknown Approved Use Unknown
Chronic myeloid leukemia 25 Sources: https://clinicaltrials.gov/ct2/show/NCT00827138	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
377 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27927766	200 mg 2 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	REBASTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
67 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27927766	114 mg 1 times / day multiple, oral dose: 114 mg route of administration: Oral experiment type: MULTIPLE co-administered:	REBASTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
114 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27927766	100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	REBASTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
308 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27927766	150 mg 2 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	REBASTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
218 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27927766	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	REBASTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
284 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27927766	1200 mg 1 times / day multiple, oral dose: 1200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	REBASTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
229 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27927766	300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	REBASTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
1180 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27927766	200 mg 2 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	REBASTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
348 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27927766	114 mg 1 times / day multiple, oral dose: 114 mg route of administration: Oral experiment type: MULTIPLE co-administered:	REBASTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
554 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27927766	100 mg 2 times / day multiple, oral dose: 100 mg route of administration: Oral experiment type: MULTIPLE co-administered:	REBASTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
786 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27927766	150 mg 2 times / day multiple, oral dose: 150 mg route of administration: Oral experiment type: MULTIPLE co-administered:	REBASTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
805 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27927766	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:	REBASTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
966 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27927766	1200 mg 1 times / day multiple, oral dose: 1200 mg route of administration: Oral experiment type: MULTIPLE co-administered:	REBASTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
528 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/27927766	300 mg 1 times / day multiple, oral dose: 300 mg route of administration: Oral experiment type: MULTIPLE co-administered:	REBASTINIB plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY111522	https://www.001chemical.com/chem/search?q=DY111522
001 Chemical	DY34067	https://www.001chemical.com/chem/search?q=DY34067
1PlusChem LLC	1P0006SI	https://www.1pchem.com/search?query=1P0006SI
AChemBlock	M15887	http://www.achemblock.com/catalogsearch/result/?q=M15887
AK Scientific	SYN5748	https://aksci.com/item_detail.php?cat=SYN5748
AK Scientific	X7511	https://aksci.com/item_detail.php?cat=X7511
AOBIOUS INC	AOB87733	http://aobious.com/aobious/search?search_query=AOB87733
Angene	AGN-PC-04Z0CH	http://www.angenechemical.com/productshow/AGN-PC-04Z0CH.html
ApexBio Technology	B1404	https://www.apexbt.com/catalogsearch/result/?q=B1404
AstaTech	42024	http://astatechinc.com/CPSResult.php?CRNO=42024
Axon MedChem	2123	https://www.axonmedchem.com/product/2123
BLD Pharm	BD280341	http://www.bldpharm.com/search/Search.html?keyword=BD280341
BOC Sciences	1020172-07-9	http://www.bocsci.com/description.asp?cas=1020172-07-9
Chem Scene	CS-1038	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1038
ChemShuttle	113196	https://www.chemshuttle.com/catalogsearch/result/?q=113196
Combi-Blocks	QJ-8369	http://www.combi-blocks.com/cgi-bin/find.cgi?QJ-8369
Debye Scientific	DA-34916	https://www.debyesci.com/index.php?id=product&ext[cno]=DA-34916
Excenen	EX-A2046	http://www.excenen.com/searchresultlist.php?id=EX-A2046
KeyOrganics	AS-17048	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-17048
Matrix Scientific	147692	http://www.matrixscientific.com/147692.html
MedChem Express	HY-13024	https://www.medchemexpress.com/search.html?q=HY-13024&ft=&fa=&fp=
MolPort	MolPort-023-293-500	https://www.molport.com/shop/molecule-link/MolPort-023-293-500
Molcore	MC111522	http://www.molcore.com/CatMC111522.html
Molcore	MC34067	http://www.molcore.com/CatMC34067.html
Molnova	M10095	https://www.molnova.com/en/serch-list.html?keywords=M10095
MuseChem	M020489	https://www.musechem.com/product/M020489.html
Ryan Scientific	101-94098	https://ryansci.com/products?q=101-94098&list_q=&search_type=exact
Ryan Scientific	GSK429286A	https://ryansci.com/products?q=GSK429286A&list_q=&search_type=exact
Selleck Chemicals	S2634	http://www.selleckchem.com/search.html?searchDTO.searchParam=S2634
ShangHai Biochempartner	BCP02345	http://www.biochempartner.com/search_BCP02345
TargetMol	T2640	https://www.targetmol.com/search?keyword=T2640
eMolecules	36516770	https://orderbb.emolecules.com/search/#?query=36516770
eNovation Chemicals	D501754	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D501754&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-6200033528	https://mcule.com/MCULE-6200033528/

PubMed

Title	Date	PubMed
		252160750
The BCR-ABL35INS insertion/truncation mutant is kinase-inactive and does not contribute to tyrosine kinase inhibitor resistance in chronic myeloid leukemia.	2011 Nov 10	21908430

Patents

Sample Use Guides

In Vivo Use Guide

150 mg twice a day tablets, continuous dosing of 28 day cycles

Route of Administration: Oral

In Vitro Use Guide

Exposure to 6 nM DCC-2036 (REBASTINIB) for 24 hours completely abolished the phosphorylation of PDGFRα in EOL-1 cells (EOL-1 cell line, derived from a patient with FIP1L1-PDGFRα-positive HES (hypereosinophilics syndrome)). DCC-2036 (0-200 nM) effectively decreased the phosphorylated-PDGFRα in BaF3 cells expressing FIP1L1-PDGFRα T674I mutant in a concentration- and time-dependent manner while the total protein level of PDGFRα was not affected. DCC-2036 inhibited proliferation, and induced apoptosis with MEK-dependent up-regulation of the pro-apoptotic protein Bim in FIP1L1-PDGFRα-positive cells.

Name

Type

Language

REBASTINIB

Official Name

English

DP-1919

Code

English

rebastinib [INN]

Common Name

English

REBASTINIB [USAN]

Common Name

English

N-(3-(1,1-DIMETHYLETHYL)-1-(QUINOLIN-6-YL)-1H-PYRAZOL-5-YL)-N'-(2-FLUORO-4-((2- (METHYLCARBAMOYL)PYRIDIN-4-YL)OXY)PHENYL)UREA

Systematic Name

English

2-PYRIDINECARBOXAMIDE, 4-(4-((((3-(1,1-DIMETHYLETHYL)-1-(6-QUINOLINYL)-1H-PYRAZOL-5-YL)AMINO)CARBONYL)AMINO)-3-FLUOROPHENOXY)-N-METHYL-

Systematic Name

English

4-(4-(((3-TERT-BUTYL-1-(QUINOLIN-6-YL)-1H-PYRAZOL-5-YL)CARBAMOYL(AMINO)-3-FLUOROPHENOXY)-N-METHYLPYRIDIN-2-CARBOXAMIDE

Common Name

English

Rebastinib [WHO-DD]

Common Name

English

DCC-2036 FREE BASE

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C129825