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Details

Stereochemistry ABSOLUTE
Molecular Formula C18H18ClF5N6O.C4H4O4.2H2O
Molecular Weight 616.923
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of CEVIPABULIN FUMARATE

SMILES

O.O.OC(=O)\C=C\C(O)=O.CNCCCOC1=CC(F)=C(C(F)=C1)C2=C(N[C@@H](C)C(F)(F)F)N3N=CN=C3N=C2Cl

InChI

InChIKey=UUFXQPPJVCARJY-CBVSRFFLSA-N
InChI=1S/C18H18ClF5N6O.C4H4O4.2H2O/c1-9(18(22,23)24)28-16-14(15(19)29-17-26-8-27-30(16)17)13-11(20)6-10(7-12(13)21)31-5-3-4-25-2;5-3(6)1-2-4(7)8;;/h6-9,25,28H,3-5H2,1-2H3;1-2H,(H,5,6)(H,7,8);2*1H2/b;2-1+;;/t9-;;;/m0.../s1

HIDE SMILES / InChI
Cevipabulin is a synthetic, water-soluble tubulin-binding agent with potential antineoplastic activity. Cevipabulin appears to bind at the vinca-binding site on tubulin but seems to act more similar to taxane-site binding agents in that it enhances tubulin polymerization and does not induce tubulin depolymerization. The disruption in microtubule dynamics may eventually inhibit cell division and reduce cellular growth.

Originator

Curator's Comment: # Wyeth Holdings Corp

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
582 ng/mL
31.5 mg/m² 1 times / week multiple, intravenous
dose: 31.5 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
CEVIPABULIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2768 ng × h/mL
31.5 mg/m² 1 times / week multiple, intravenous
dose: 31.5 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
CEVIPABULIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
27.2 h
31.5 mg/m² 1 times / week multiple, intravenous
dose: 31.5 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
CEVIPABULIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
31.5 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 31.5 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 31.5 mg/m2, 1 times / week
Sources: Page: p.268
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources: Page: p.268
DLT: Febrile neutropenia...
Disc. AE: Neutropenia...
Dose limiting toxicities:
Febrile neutropenia (14.3%)
AEs leading to
discontinuation/dose reduction:
Neutropenia (grade 3-4, 42.9%)
Sources: Page: p.268
AEs

AEs

AESignificanceDosePopulation
Febrile neutropenia 14.3%
DLT
31.5 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 31.5 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 31.5 mg/m2, 1 times / week
Sources: Page: p.268
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources: Page: p.268
Neutropenia grade 3-4, 42.9%
Disc. AE
31.5 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 31.5 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 31.5 mg/m2, 1 times / week
Sources: Page: p.268
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources: Page: p.268
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no

Sample Use Guides

Patients were treated with TTI-237 (Cevipabulin) intravenously on days 1, 8 and 15 of a 28-day cycle at dose of 4.5, 9, 15, 22.5 and 31.5 mg/m2 .
Route of Administration: Intravenous
HeLa cells were harvested by trypsinization, washed, counted, and distributed to wells of 96-well flat-bottomed microtiter plates at 1,000 cells per well in 200 AL of medium. All plates were incubated at 37C in humidified 5% CO2 in air for ~24 h. On day 2, compounds for test were diluted and added to wells. Compounds were dissolved in DMSO at 10 to 20 mkmol/L. For each compound, nine serial 2-fold dilutions were prepared in DMSO. Ten microliters of each dilution was transferred to 100 mkL of medium and mixed well, and then 5 AL of this dilution were transferred in triplicate or quadruplicate to wells containing cells. The final high concentration of each compound was typically 5 mkmol/L. All cultures, including controls with no compound, contained a final concentration of 0.27% DMSO. After 3 d of culture with test compounds (day 5 overall), the MTS assay (Promega; CellTiter 96 aqueous nonradioactive cell proliferation assay) was done on all wells.
Name Type Language
CEVIPABULIN FUMARATE
USAN   WHO-DD  
USAN  
Official Name English
CEVIPABULIN FUMARATE [USAN]
Common Name English
(1,2,4)TRIAZOLO(1,5-A)PYRIMIDIN-7-AMINE, 5-CHLORO-6-(2,6-DIFLUORO-4-(3-(METHYLAMINO)PROPOXY)PHENYL)-N-((1S)-2,2,2-TRIFLUORO-1-METHYLETHYL)-, (2E)-2-BUTENEDIOATE (1:1), DIHYDRATE
Common Name English
TTI-237 FUMARATE DIHYDRATE
Code English
5-Chloro-6-[2,6-difluoro-4-[3-(methylamino)propoxy]phenyl]-N-[(1S)-2,2,2-trifluoro-1-methylethyl]-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine (2E)-but-2-enedioate (1:1) dihydrate
Common Name English
Cevipabulin fumarate [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C25974
Created by admin on Fri Dec 15 16:10:11 GMT 2023 , Edited by admin on Fri Dec 15 16:10:11 GMT 2023
Code System Code Type Description
CAS
849550-69-2
Created by admin on Fri Dec 15 16:10:11 GMT 2023 , Edited by admin on Fri Dec 15 16:10:11 GMT 2023
PRIMARY
NCI_THESAURUS
C73815
Created by admin on Fri Dec 15 16:10:11 GMT 2023 , Edited by admin on Fri Dec 15 16:10:11 GMT 2023
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FDA UNII
Q380BYV049
Created by admin on Fri Dec 15 16:10:11 GMT 2023 , Edited by admin on Fri Dec 15 16:10:11 GMT 2023
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ChEMBL
CHEMBL1182714
Created by admin on Fri Dec 15 16:10:11 GMT 2023 , Edited by admin on Fri Dec 15 16:10:11 GMT 2023
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PUBCHEM
16088020
Created by admin on Fri Dec 15 16:10:11 GMT 2023 , Edited by admin on Fri Dec 15 16:10:11 GMT 2023
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SMS_ID
300000044474
Created by admin on Fri Dec 15 16:10:11 GMT 2023 , Edited by admin on Fri Dec 15 16:10:11 GMT 2023
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USAN
SS-31
Created by admin on Fri Dec 15 16:10:11 GMT 2023 , Edited by admin on Fri Dec 15 16:10:11 GMT 2023
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EPA CompTox
DTXSID60582094
Created by admin on Fri Dec 15 16:10:11 GMT 2023 , Edited by admin on Fri Dec 15 16:10:11 GMT 2023
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