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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 of REBASTINIB

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

Molecular Formula C30H28FN7O3
Molecular Weight 553.5868
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
2.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
377 ng/mL
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
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
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
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
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
1180 ng × h/mL
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
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
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
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
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
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
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

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Patents

Sample Use Guides

150 mg twice a day tablets, continuous dosing of 28 day cycles
Route of Administration: Oral
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.
Substance Class Chemical
Created
by admin
on Sat Dec 16 01:49:52 UTC 2023
Edited
by admin
on Sat Dec 16 01:49:52 UTC 2023
Record UNII
75017Q6I97
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
REBASTINIB
INN   USAN   WHO-DD  
INN   USAN  
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
Created by admin on Sat Dec 16 01:49:52 UTC 2023 , Edited by admin on Sat Dec 16 01:49:52 UTC 2023
FDA ORPHAN DRUG 637018
Created by admin on Sat Dec 16 01:49:52 UTC 2023 , Edited by admin on Sat Dec 16 01:49:52 UTC 2023
Code System Code Type Description
FDA UNII
75017Q6I97
Created by admin on Sat Dec 16 01:49:52 UTC 2023 , Edited by admin on Sat Dec 16 01:49:52 UTC 2023
PRIMARY
PUBCHEM
25066467
Created by admin on Sat Dec 16 01:49:52 UTC 2023 , Edited by admin on Sat Dec 16 01:49:52 UTC 2023
PRIMARY
ChEMBL
CHEMBL1738757
Created by admin on Sat Dec 16 01:49:52 UTC 2023 , Edited by admin on Sat Dec 16 01:49:52 UTC 2023
PRIMARY
CAS
1020172-07-9
Created by admin on Sat Dec 16 01:49:52 UTC 2023 , Edited by admin on Sat Dec 16 01:49:52 UTC 2023
PRIMARY
NCI_THESAURUS
C152162
Created by admin on Sat Dec 16 01:49:52 UTC 2023 , Edited by admin on Sat Dec 16 01:49:52 UTC 2023
PRIMARY
SMS_ID
100000163525
Created by admin on Sat Dec 16 01:49:52 UTC 2023 , Edited by admin on Sat Dec 16 01:49:52 UTC 2023
PRIMARY
EVMPD
SUB177831
Created by admin on Sat Dec 16 01:49:52 UTC 2023 , Edited by admin on Sat Dec 16 01:49:52 UTC 2023
PRIMARY
EPA CompTox
DTXSID40144533
Created by admin on Sat Dec 16 01:49:52 UTC 2023 , Edited by admin on Sat Dec 16 01:49:52 UTC 2023
PRIMARY
USAN
ZZ-63
Created by admin on Sat Dec 16 01:49:52 UTC 2023 , Edited by admin on Sat Dec 16 01:49:52 UTC 2023
PRIMARY
DRUG BANK
DB13005
Created by admin on Sat Dec 16 01:49:52 UTC 2023 , Edited by admin on Sat Dec 16 01:49:52 UTC 2023
PRIMARY
INN
9685
Created by admin on Sat Dec 16 01:49:52 UTC 2023 , Edited by admin on Sat Dec 16 01:49:52 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
IC50
TARGET -> INHIBITOR
IC50
Related Record Type Details
ACTIVE MOIETY