U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C24H30N6O2
Molecular Weight 434.534
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LEXIBULIN

SMILES

CCC[C@H](NC1=NC(=NC=C1C)C2=CC(OC)=C(NC(=O)NCC)C=C2)C3=CC=CN=C3

InChI

InChIKey=MTJHLONVHHPNSI-IBGZPJMESA-N
InChI=1S/C24H30N6O2/c1-5-8-19(18-9-7-12-25-15-18)28-22-16(3)14-27-23(30-22)17-10-11-20(21(13-17)32-4)29-24(31)26-6-2/h7,9-15,19H,5-6,8H2,1-4H3,(H2,26,29,31)(H,27,28,30)/t19-/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including http://eprints.whiterose.ac.uk/86822/ http://adisinsight.springer.com/drugs/800022992

CYT997 (Lexibulin) is a wholly synthetic compound that possesses highly potent cytotoxic activity in vitro through inhibition of microtubule polymerization. CYT997 (Lexibulin) is a potent microtubule polymerization inhibitor with IC50 of 10-100 nM in cancer cell lines. CYT997 (Lexibulin) blocks the cell cycle at the G(2)-M boundary, and Western blot analysis indicates an increase in phosphorylated Bcl-2, along with increased expression of cyclin B1. Caspase-3 activation is also observed in cells treated with CYT997 (Lexibulin) along with the generation of poly(ADP-ribose) polymerase. The compound possesses favorable pharmacokinetic properties, is orally bioavailable, and is efficacious per os in a range of in vivo cancer models, including some refractory to paclitaxel treatment. CYT997 (Lexibulin) exhibits vascular disrupting activity as measured in vitro by effects on the permeability of human umbilical vein endothelial cell monolayers, and in vivo by effects on tumor blood flow. CYT997 (Lexibulin) possesses a useful combination of pharmacologic and pharmacokinetic properties having considerable potential as a novel anticancer agent. Lexibulin was being developed by YM BioSciences as a vascular-disrupting agent (VDA) for the potential treatment of cancer, it was in phase II development on YM BioSciences ' pipeline. It appears that the development of lexibulin has been discontinued.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
59.0 nM [IC50]
Target ID: CHEMBL2366066
83.5 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
376.2 ng/mL
164 mg/m² 1 times / 2 weeks multiple, oral
dose: 164 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LEXIBULIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
320 ng/mL
164 mg/m² single, oral
dose: 164 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
LEXIBULIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
5640 ng × h/mL
358 mg/m² 1 times / 3 weeks multiple, intravenous
dose: 358 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
LEXIBULIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
1315 ng × h/mL
164 mg/m² 1 times / 2 weeks multiple, oral
dose: 164 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LEXIBULIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
941.5 ng × h/mL
164 mg/m² single, oral
dose: 164 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
LEXIBULIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
4.6 h
358 mg/m² 1 times / 3 weeks multiple, intravenous
dose: 358 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
LEXIBULIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2.44 h
164 mg/m² 1 times / 2 weeks multiple, oral
dose: 164 mg/m²
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LEXIBULIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
4.28 h
164 mg/m² single, oral
dose: 164 mg/m²
route of administration: Oral
experiment type: SINGLE
co-administered:
LEXIBULIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
164 mg/m2 1 times / 2 weeks multiple, oral
MTD
Dose: 164 mg/m2, 1 times / 2 weeks
Route: oral
Route: multiple
Dose: 164 mg/m2, 1 times / 2 weeks
Sources: Page: p.130
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 6
Sources: Page: p.130
DLT: Hypoxia, Fatigue...
Other AEs: Anaemia...
Dose limiting toxicities:
Hypoxia (grade 3, 16.7%)
Fatigue (grade 3, 16.7%)
Fatigue (grade 3, 16.7%)
Other AEs:
Anaemia (grade 3, 16.7%)
Sources: Page: p.130
358 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 358 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 358 mg/m2, 1 times / 3 weeks
Sources: Page: p.600
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.600
DLT: Hypoxia, QT interval prolonged...
Other AEs: Dyspnea...
Dose limiting toxicities:
Hypoxia (grade 3, 33.3%)
QT interval prolonged (grade 3, 33.3%)
Dyspnea (grade 4, 33.3%)
Other AEs:
Dyspnea (grade 3, 33.3%)
Sources: Page: p.600
AEs

AEs

AESignificanceDosePopulation
Anaemia grade 3, 16.7%
164 mg/m2 1 times / 2 weeks multiple, oral
MTD
Dose: 164 mg/m2, 1 times / 2 weeks
Route: oral
Route: multiple
Dose: 164 mg/m2, 1 times / 2 weeks
Sources: Page: p.130
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 6
Sources: Page: p.130
Fatigue grade 3, 16.7%
DLT
164 mg/m2 1 times / 2 weeks multiple, oral
MTD
Dose: 164 mg/m2, 1 times / 2 weeks
Route: oral
Route: multiple
Dose: 164 mg/m2, 1 times / 2 weeks
Sources: Page: p.130
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 6
Sources: Page: p.130
Fatigue grade 3, 16.7%
DLT, Disc. AE
164 mg/m2 1 times / 2 weeks multiple, oral
MTD
Dose: 164 mg/m2, 1 times / 2 weeks
Route: oral
Route: multiple
Dose: 164 mg/m2, 1 times / 2 weeks
Sources: Page: p.130
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 6
Sources: Page: p.130
Hypoxia grade 3, 16.7%
DLT, Disc. AE
164 mg/m2 1 times / 2 weeks multiple, oral
MTD
Dose: 164 mg/m2, 1 times / 2 weeks
Route: oral
Route: multiple
Dose: 164 mg/m2, 1 times / 2 weeks
Sources: Page: p.130
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 6
Sources: Page: p.130
Dyspnea grade 3, 33.3%
358 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 358 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 358 mg/m2, 1 times / 3 weeks
Sources: Page: p.600
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.600
QT interval prolonged grade 3, 33.3%
DLT
358 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 358 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 358 mg/m2, 1 times / 3 weeks
Sources: Page: p.600
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.600
Hypoxia grade 3, 33.3%
DLT, Disc. AE
358 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 358 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 358 mg/m2, 1 times / 3 weeks
Sources: Page: p.600
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.600
Dyspnea grade 4, 33.3%
DLT, Disc. AE
358 mg/m2 1 times / 3 weeks multiple, intravenous
MTD
Dose: 358 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 358 mg/m2, 1 times / 3 weeks
Sources: Page: p.600
unhealthy, ADULT
n = 3
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 3
Sources: Page: p.600
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
inconclusive [IC50 0.0008 uM]
PubMed

PubMed

TitleDatePubMed
Patents

Sample Use Guides

Escalating doses (100mg/m^2 to 150mg/m^2), 24-hour intravenous infusion on Day 2 of a 21-day cycle
Route of Administration: Intravenous
Treatment of NCI-H929 and U266 under standard culture conditions with 50 or 100 nM CYT997 (Lexibulin) for 72 h demonstrated almost complete cytostasis
Name Type Language
LEXIBULIN
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
CYT 997
Code English
CYT-997
Code English
LEXIBULIN [USAN]
Common Name English
1-ETHYL-3-(2-METHOXY-4-(5-METHYL-4-(((1S)-1-(PYRIDIN-3-YL)BUTYL)AMINO)PYRIMIDIN-2-YL)PHENYL)UREA
Systematic Name English
UREA, N-ETHYL-N'-(2-METHOXY-4-(5-METHYL-4-(((1S)-1-(3-PYRIDINYL)BUTYL)AMINO)-2-PYRIMIDINYL)PHENYL)-
Systematic Name English
CYT997
Code English
lexibulin [INN]
Common Name English
Lexibulin [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C25974
Created by admin on Sat Dec 16 16:56:20 GMT 2023 , Edited by admin on Sat Dec 16 16:56:20 GMT 2023
Code System Code Type Description
PUBCHEM
11351021
Created by admin on Sat Dec 16 16:56:20 GMT 2023 , Edited by admin on Sat Dec 16 16:56:20 GMT 2023
PRIMARY
ChEMBL
CHEMBL552212
Created by admin on Sat Dec 16 16:56:20 GMT 2023 , Edited by admin on Sat Dec 16 16:56:20 GMT 2023
PRIMARY
INN
9481
Created by admin on Sat Dec 16 16:56:20 GMT 2023 , Edited by admin on Sat Dec 16 16:56:20 GMT 2023
PRIMARY
SMS_ID
300000034308
Created by admin on Sat Dec 16 16:56:20 GMT 2023 , Edited by admin on Sat Dec 16 16:56:20 GMT 2023
PRIMARY
CAS
917111-44-5
Created by admin on Sat Dec 16 16:56:20 GMT 2023 , Edited by admin on Sat Dec 16 16:56:20 GMT 2023
PRIMARY
NCI_THESAURUS
C77882
Created by admin on Sat Dec 16 16:56:20 GMT 2023 , Edited by admin on Sat Dec 16 16:56:20 GMT 2023
PRIMARY
EPA CompTox
DTXSID10238675
Created by admin on Sat Dec 16 16:56:20 GMT 2023 , Edited by admin on Sat Dec 16 16:56:20 GMT 2023
PRIMARY
USAN
XX-161
Created by admin on Sat Dec 16 16:56:20 GMT 2023 , Edited by admin on Sat Dec 16 16:56:20 GMT 2023
PRIMARY
DRUG BANK
DB05147
Created by admin on Sat Dec 16 16:56:20 GMT 2023 , Edited by admin on Sat Dec 16 16:56:20 GMT 2023
PRIMARY
FDA UNII
2GTU230HA1
Created by admin on Sat Dec 16 16:56:20 GMT 2023 , Edited by admin on Sat Dec 16 16:56:20 GMT 2023
PRIMARY