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

Details

Stereochemistry ACHIRAL
Molecular Formula C17H17N3O
Molecular Weight 279.3364
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of VERUBULIN

SMILES

COC1=CC=C(C=C1)N(C)C2=NC(C)=NC3=C2C=CC=C3

InChI

InChIKey=SNHCRNMVYDHVDT-UHFFFAOYSA-N
InChI=1S/C17H17N3O/c1-12-18-16-7-5-4-6-15(16)17(19-12)20(2)13-8-10-14(21-3)11-9-13/h4-11H,1-3H3

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800022153 | http://www.prnewswire.com/news-releases/new-data-suggests-improved-tumor-response-for-the-combination-of-azixa-and-immune-checkpoint-inhibitors-in-the-treatment-of-cancer-300291030.html

Veribulin is a novel microtubule destabilizer that both functions as a potent cytotoxin and acts as a vascular disrupting agent (VDA). It binds to the same (or nearby) sites on β-tubulin as colchicine. It is capable of evading multidrug resistance pumps and, thus, achieves high CNS concentrations. It is efficacious in multiple xenograft models without CNS toxicity. Veribulin had previously demonstrated pre-clinical and clinical activity in multiple tumor types. Veribulin is in phase II clinical trial for the treatment of Glioblastoma and Malignant melanoma.

Approval Year

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
21.3 ng/mL
3.3 mg/m² 1 times / week multiple, intravenous
dose: 3.3 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
VERUBULIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
30.7 ng/mL
3.9 mg/m² 1 times / week multiple, intravenous
dose: 3.9 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
VERUBULIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
62 ng/mL
4.5 mg/m² 1 times / week multiple, intravenous
dose: 4.5 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
VERUBULIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
116.8 ng × h/mL
3.3 mg/m² 1 times / week multiple, intravenous
dose: 3.3 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
VERUBULIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
139.3 ng × h/mL
3.9 mg/m² 1 times / week multiple, intravenous
dose: 3.9 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
VERUBULIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
183.6 ng × h/mL
4.5 mg/m² 1 times / week multiple, intravenous
dose: 4.5 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
VERUBULIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
6.4 h
3.3 mg/m² 1 times / week multiple, intravenous
dose: 3.3 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
VERUBULIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
7.5 h
3.9 mg/m² 1 times / week multiple, intravenous
dose: 3.9 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
VERUBULIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
5.7 h
4.5 mg/m² 1 times / week multiple, intravenous
dose: 4.5 mg/m²
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
VERUBULIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
4.5 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 4.5 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 4.5 mg/m2, 1 times / week
Sources: Page: p.3413
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources: Page: p.3413
DLT: Myocardial infarction...
Dose limiting toxicities:
Myocardial infarction (grade 3, 14.3%)
Sources: Page: p.3413
3.3 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 3.3 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 3.3 mg/m2, 1 times / week
Sources: Page: p.3413
unhealthy, ADULT
n = 13
Health Status: unhealthy
Condition: cance
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 13
Sources: Page: p.3413
3.3 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 3.3 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 3.3 mg/m2, 1 times / week
Sources: Page: p.338
unhealthy, ADULT
n = 31
Health Status: unhealthy
Condition: glioblastoma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 31
Sources: Page: p.338
Disc. AE: Myocardial infarction...
AEs leading to
discontinuation/dose reduction:
Myocardial infarction (grade 4, 3.2%)
Sources: Page: p.338
3.9 mg/m2 1 times / week multiple, intravenous
Studied dose
Dose: 3.9 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 3.9 mg/m2, 1 times / week
Sources: Page: p.3413
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.3413
DLT: Myocardial infarction...
Dose limiting toxicities:
Myocardial infarction (grade 3, 16.7%)
Sources: Page: p.3413
AEs

AEs

AESignificanceDosePopulation
Myocardial infarction grade 3, 14.3%
DLT
4.5 mg/m2 1 times / week multiple, intravenous
Highest studied dose
Dose: 4.5 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 4.5 mg/m2, 1 times / week
Sources: Page: p.3413
unhealthy, ADULT
n = 7
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 7
Sources: Page: p.3413
Myocardial infarction grade 4, 3.2%
Disc. AE
3.3 mg/m2 1 times / week multiple, intravenous
MTD
Dose: 3.3 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 3.3 mg/m2, 1 times / week
Sources: Page: p.338
unhealthy, ADULT
n = 31
Health Status: unhealthy
Condition: glioblastoma
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 31
Sources: Page: p.338
Myocardial infarction grade 3, 16.7%
DLT
3.9 mg/m2 1 times / week multiple, intravenous
Studied dose
Dose: 3.9 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 3.9 mg/m2, 1 times / week
Sources: Page: p.3413
unhealthy, ADULT
n = 6
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 6
Sources: Page: p.3413
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer





Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Discovery of N-(4-methoxyphenyl)-N,2-dimethylquinazolin-4-amine, a potent apoptosis inducer and efficacious anticancer agent with high blood brain barrier penetration.
2009 Apr 23
Discovery of N-methyl-4-(4-methoxyanilino)quinazolines as potent apoptosis inducers. Structure-activity relationship of the quinazoline ring.
2010 Apr 1
Patents

Patents

Sample Use Guides

Verubulin was administered at 3.3 mg/m(2) as a 2-h intravenous infusion once weekly for 3 consecutive weeks in a 4-week cycle.
Route of Administration: Intravenous
Verubulin was highly active in HCT116 and SNU-398 cells with EC50 values of 3 nM and 2 nM, respectively, similar to its high activity in T47D cells.
Name Type Language
VERUBULIN
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
4-QUINAZOLINAMINE, N-(4-METHOXYPHENYL)-N,2-DIMETHYL-
Systematic Name English
Verubulin [WHO-DD]
Common Name English
MX-128495
Code English
verubulin [INN]
Common Name English
N-(4-Methoxyphenyl)-N,2-dimethylquinazolin-4-amine
Systematic Name English
VERUBULIN [USAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C25974
Created by admin on Fri Dec 15 18:33:23 GMT 2023 , Edited by admin on Fri Dec 15 18:33:23 GMT 2023
Code System Code Type Description
SMS_ID
300000034479
Created by admin on Fri Dec 15 18:33:23 GMT 2023 , Edited by admin on Fri Dec 15 18:33:23 GMT 2023
PRIMARY
PUBCHEM
11414799
Created by admin on Fri Dec 15 18:33:23 GMT 2023 , Edited by admin on Fri Dec 15 18:33:23 GMT 2023
PRIMARY
CAS
827031-83-4
Created by admin on Fri Dec 15 18:33:23 GMT 2023 , Edited by admin on Fri Dec 15 18:33:23 GMT 2023
PRIMARY
INN
9253
Created by admin on Fri Dec 15 18:33:23 GMT 2023 , Edited by admin on Fri Dec 15 18:33:23 GMT 2023
PRIMARY
FDA UNII
X97O9FTB92
Created by admin on Fri Dec 15 18:33:23 GMT 2023 , Edited by admin on Fri Dec 15 18:33:23 GMT 2023
PRIMARY
NCI_THESAURUS
C96747
Created by admin on Fri Dec 15 18:33:23 GMT 2023 , Edited by admin on Fri Dec 15 18:33:23 GMT 2023
PRIMARY
MESH
C522974
Created by admin on Fri Dec 15 18:33:23 GMT 2023 , Edited by admin on Fri Dec 15 18:33:23 GMT 2023
PRIMARY
DRUG BANK
DB05585
Created by admin on Fri Dec 15 18:33:23 GMT 2023 , Edited by admin on Fri Dec 15 18:33:23 GMT 2023
PRIMARY
USAN
UU-20
Created by admin on Fri Dec 15 18:33:23 GMT 2023 , Edited by admin on Fri Dec 15 18:33:23 GMT 2023
PRIMARY
ChEMBL
CHEMBL492399
Created by admin on Fri Dec 15 18:33:23 GMT 2023 , Edited by admin on Fri Dec 15 18:33:23 GMT 2023
PRIMARY