CEVIPABULIN FUMARATE

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 Search

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

Molecular Formula	H2O
Molecular Weight	18.0153
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C18H18ClF5N6O
Molecular Weight	464.82
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	C4H4O4
Molecular Weight	116.0722
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18381436

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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tubulin 69 Target ID: CHEMBL2095182 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18381436	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Advanced malignant solid tumors 6 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20697774	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
582 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20697774	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

Value	Dose	Co-administered	Analyte	Population
2768 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20697774	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
27.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20697774	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

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/20697774 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: https://pubmed.ncbi.nlm.nih.gov/20697774 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: https://pubmed.ncbi.nlm.nih.gov/20697774 Page: p.268

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/20697774 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: https://pubmed.ncbi.nlm.nih.gov/20697774 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: https://pubmed.ncbi.nlm.nih.gov/20697774 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: https://pubmed.ncbi.nlm.nih.gov/20697774 Page: p.268

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1182022#sid=242094732	no

PubMed

Title	Date	PubMed

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:10:11 GMT 2023` Edited by `admin` on `Fri Dec 15 16:10:11 GMT 2023`
Record UNII	Q380BYV049
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CEVIPABULIN FUMARATE

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