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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.

CNS Activity

Originator

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Binding Agent
1064
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase I
428
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
21.3 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/21159616
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/21159616
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/21159616
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/21159616
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/21159616
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/21159616
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/21159616
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/21159616
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
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/21159616
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:
https://pubmed.ncbi.nlm.nih.gov/21159616
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:
https://pubmed.ncbi.nlm.nih.gov/21159616
Page: p.3413
DLT: Myocardial infarction...
Dose limiting toxicities:
Myocardial infarction (grade 3, 14.3%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/21159616
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:
https://pubmed.ncbi.nlm.nih.gov/21159616
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:
https://pubmed.ncbi.nlm.nih.gov/21159616
Page: p.3413
Sources:
https://pubmed.ncbi.nlm.nih.gov/21159616
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:
https://pubmed.ncbi.nlm.nih.gov/24740196
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:
https://pubmed.ncbi.nlm.nih.gov/24740196
Page: p.338
Disc. AE: Myocardial infarction...
AEs leading to
discontinuation/dose reduction:
Myocardial infarction (grade 4, 3.2%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/24740196
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:
https://pubmed.ncbi.nlm.nih.gov/21159616
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:
https://pubmed.ncbi.nlm.nih.gov/21159616
Page: p.3413
DLT: Myocardial infarction...
Dose limiting toxicities:
Myocardial infarction (grade 3, 16.7%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/21159616
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:
https://pubmed.ncbi.nlm.nih.gov/21159616
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:
https://pubmed.ncbi.nlm.nih.gov/21159616
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:
https://pubmed.ncbi.nlm.nih.gov/24740196
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:
https://pubmed.ncbi.nlm.nih.gov/24740196
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:
https://pubmed.ncbi.nlm.nih.gov/21159616
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:
https://pubmed.ncbi.nlm.nih.gov/21159616
Page: p.3413
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
substrate
1737
inhibitor
1612

OverviewOther

Other InhibitorOther SubstrateOther Inducer
MRP1
107

P-gp
1537

BCRP
561

CYP2C19
991

CYP1A2
1054
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
BCRP
561
 no
MRP1
107
 no
P-gp
1537
 no
CYP1A2
1054
 yes
CYP2C19
991
 yes
CYP3A4
1737
 yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
hERG
1647
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

20050137213
2

Sample Use Guides

In Vivo Use Guide
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
In Vitro Use Guide
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
ACTIVE MOIETY
Structure of VERUBULIN
SALT/SOLVATE (PARENT)
Structure of VERUBULIN HYDROCHLORIDE
NIH
NCATS
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ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
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