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

Details

Stereochemistry ABSOLUTE
Molecular Formula C34H50N8O3.3ClH
Molecular Weight 728.195
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Volasertib Trihydrochloride

SMILES

Cl.Cl.Cl.CC[C@H]1N(C(C)C)C2=NC(NC3=CC=C(C=C3OC)C(=O)N[C@H]4CC[C@@H](CC4)N5CCN(CC6CC6)CC5)=NC=C2N(C)C1=O

InChI

InChIKey=JFEPFDDQDQBWIL-VCVQLDHKSA-N
InChI=1S/C34H50N8O3.3ClH/c1-6-28-33(44)39(4)29-20-35-34(38-31(29)42(28)22(2)3)37-27-14-9-24(19-30(27)45-5)32(43)36-25-10-12-26(13-11-25)41-17-15-40(16-18-41)21-23-7-8-23;;;/h9,14,19-20,22-23,25-26,28H,6-8,10-13,15-18,21H2,1-5H3,(H,36,43)(H,35,37,38);3*1H/t25-,26-,28-;;;/m1.../s1

HIDE SMILES / InChI
Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula C34H50N8O3
Molecular Weight 618.8126
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/19383823

Volasertib (BI 6727), a dihydropteridinone derivative, is a small-molecule cell cycle inhibitor of polo-like kinase-1 (PLK-1). Volasertib induces G2-M arrest and induction of apoptosis in cancer cells and potently inhibits tumor growth in xenograft models. Boehringer Ingelheim is developing intravenously administered volasertib for the treatment of acute myeloid leukaemia (AML), myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML), non-small cell lung cancer, urogenital cancer, ovarian cancer and solid tumours.

CNS Activity

CNS Penetrant
2588
Curator's Comment: Volasertib (BI 6727) can cross an in vitro blood-brain barrier model. In vivo, volasertib induced regressions of brain tumors in several xenograft models. No human data available.

Originator

Approval Year

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8504
 0.87 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase III
665
Unknown

Approved Use

Unknown
Primary
Phase II
1147
Unknown

Approved Use

Unknown
Primary
Phase II
1147
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
501 ng/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/26627079
300 mg 1 times / day steady-state, intravenous
dose: 300 mg
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
VOLASERTIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
5300 ng × h/mL
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/26627079
300 mg 1 times / day steady-state, intravenous
dose: 300 mg
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
VOLASERTIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
112 h
EXPERIMENT
https://www.ncbi.nlm.nih.gov/pubmed/26627079
300 mg 1 times / day steady-state, intravenous
dose: 300 mg
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
VOLASERTIB plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
450 mg 1 times / 3 weeks multiple, intravenous
Highest studied dose
Dose: 450 mg, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 450 mg, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
DLT: Neutropenia, Thrombocytopenia...
Dose limiting toxicities:
Neutropenia (grade 4, 100%)
Thrombocytopenia (grade 4, 100%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
300 mg 1 times / 3 weeks multiple, intravenous
MTD
Dose: 300 mg, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 300 mg, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/26627079
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/26627079
Sources:
https://pubmed.ncbi.nlm.nih.gov/26627079
400 mg 1 times / 3 weeks multiple, intravenous
MTD
Dose: 400 mg, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 400 mg, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
DLT: Febrile neutropenia, Neutropenia...
Disc. AE: Neutropenia...
Dose limiting toxicities:
Febrile neutropenia (grade 4, 20%)
Neutropenia (grade 4, 30%)
Neutropenia (grade 3, 10%)
Thrombocytopenia (grade 4, 20%)
AEs leading to
discontinuation/dose reduction:
Neutropenia (10%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
300 mg 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 300 mg, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 300 mg, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
DLT: Thrombocytopenia, Febrile neutropenia...
Dose limiting toxicities:
Thrombocytopenia (grade 4, 6.8%)
Febrile neutropenia (grade 3, 3.4%)
Neutropenia (grade 4, 6.8%)
QT interval prolonged (grade 3, 3.4%)
Neutropenia (grade 3, 3.4%)
Fatigue (grade 3, 3.4%)
Weight decreased (grade 3, 3.4%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
350 mg 1 times / 3 weeks multiple, intravenous
Studied dose
Dose: 350 mg, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 350 mg, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/26627079
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/26627079
DLT: Neutropenia, Thrombocytopenia...
Dose limiting toxicities:
Neutropenia (grade 4, 33.3%)
Thrombocytopenia (grade 4, 33.3%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/26627079
AEs

AEs

AESignificanceDosePopulation
Neutropenia grade 4, 100%
DLT
450 mg 1 times / 3 weeks multiple, intravenous
Highest studied dose
Dose: 450 mg, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 450 mg, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Thrombocytopenia grade 4, 100%
DLT
450 mg 1 times / 3 weeks multiple, intravenous
Highest studied dose
Dose: 450 mg, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 450 mg, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Neutropenia 10%
Disc. AE
400 mg 1 times / 3 weeks multiple, intravenous
MTD
Dose: 400 mg, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 400 mg, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Neutropenia grade 3, 10%
DLT
400 mg 1 times / 3 weeks multiple, intravenous
MTD
Dose: 400 mg, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 400 mg, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Febrile neutropenia grade 4, 20%
DLT
400 mg 1 times / 3 weeks multiple, intravenous
MTD
Dose: 400 mg, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 400 mg, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Thrombocytopenia grade 4, 20%
DLT
400 mg 1 times / 3 weeks multiple, intravenous
MTD
Dose: 400 mg, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 400 mg, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Neutropenia grade 4, 30%
DLT
400 mg 1 times / 3 weeks multiple, intravenous
MTD
Dose: 400 mg, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 400 mg, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Febrile neutropenia grade 3, 3.4%
DLT
300 mg 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 300 mg, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 300 mg, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Neutropenia grade 3, 3.4%
DLT
300 mg 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 300 mg, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 300 mg, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
QT interval prolonged grade 3, 3.4%
DLT
300 mg 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 300 mg, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 300 mg, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Fatigue grade 3, 3.4%
DLT, Disc. AE
300 mg 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 300 mg, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 300 mg, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Weight decreased grade 3, 3.4%
DLT, Disc. AE
300 mg 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 300 mg, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 300 mg, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Neutropenia grade 4, 6.8%
DLT
300 mg 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 300 mg, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 300 mg, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Thrombocytopenia grade 4, 6.8%
DLT
300 mg 1 times / 3 weeks multiple, intravenous
RP2D
Dose: 300 mg, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 300 mg, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Neutropenia grade 4, 33.3%
DLT
350 mg 1 times / 3 weeks multiple, intravenous
Studied dose
Dose: 350 mg, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 350 mg, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/26627079
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/26627079
Thrombocytopenia grade 4, 33.3%
DLT
350 mg 1 times / 3 weeks multiple, intravenous
Studied dose
Dose: 350 mg, 1 times / 3 weeks
Route: intravenous
Route: multiple
Dose: 350 mg, 1 times / 3 weeks
Sources:
https://pubmed.ncbi.nlm.nih.gov/26627079
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/26627079
Sourcing

Sourcing

Vendor/AggregatorIDURL
AstaTech
42700
http://astatechinc.com/CPSResult.php?CRNO=42700
eMolecules
195316587
https://orderbb.emolecules.com/search/#?query=195316587
eMolecules
206905235
https://orderbb.emolecules.com/search/#?query=206905235
eMolecules
300524998
https://orderbb.emolecules.com/search/#?query=300524998
eMolecules
300525254
https://orderbb.emolecules.com/search/#?query=300525254
eMolecules
95469083
https://orderbb.emolecules.com/search/#?query=95469083
Hairui
VOJL009
http://www.hairuichem.com/en/product/search.do?q=VOJL009
Lab Seeker
SC-95532
http://www.labseeker.com/search.php?keywords=SC-95532&category=0
LabSeeker
SC-95532
http://www.labseeker.com/search.php?keywords=SC-95532&category=0
MuseChem
I004793
https://www.musechem.com/product/I004793.html
PI Chemicals
PI-44595
http://www.pipharm.com/catalog_products/PI-44595.html
Selleck Chemicals
S2235
http://www.selleckchem.com/search.html?searchDTO.searchParam=S2235
Synovel
SN-0140
http://www.synovellab.com/?s=SN-0140&submit=Search
Synthonix
SL100062
http://www.synthon-lab.com/search.php?cas_or_id=SL100062&cas_id_field=1
TargetMol
T6019
https://www.targetmol.com/search?keyword=T6019
Vesino Industrial Co Ltd
VA12006
http://www.vsnchem.com/search.do?a=s&psize=20&q=VA12006
PubMed

PubMed

TitleDatePubMed
Hit to Lead optimization of a novel class of squarate-containing polo-like kinases inhibitors.
2012-12-15
Polo-like kinase (PLK) inhibitors in preclinical and early clinical development in oncology.
2009-06
Use of the novel Plk1 inhibitor ZK-thiazolidinone to elucidate functions of Plk1 in early and late stages of mitosis.
2007-10
Polo-like kinases and the orchestration of cell division.
2004-06
Patents

Patents

WO/2012/072505A1
3
WO/2014/083058A1
3
WO/2015/011235A1
3
WO/2015/180552A1
3

Sample Use Guides

In Vivo Use Guide
Volasertib had a manageable safety profile up to maximum tolerated dose determined as 300 mg (a single dose by intravenous infusion over 2 h on day 1 every 21 days until disease progression or unacceptable toxicity)
Route of Administration: Intravenous
In Vitro Use Guide
Volasertib inhibited proliferation in all 40 cell lines tested, with a mean half-maximal growth inhibitory concentration of 313 nmol/l (range: 4-5000 nmol/l).
Substance Class Chemical
Created
by admin
on Wed Apr 02 18:29:56 GMT 2025
Edited
by admin
on Wed Apr 02 18:29:56 GMT 2025
Record UNII
O72812O5MN
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
Volasertib Trihydrochloride
USAN   WHO-DD  
USAN  
Official Name English
Benzamide, N-[trans-4-[4-(cyclopropylmethyl)-1-piperazinyl]cyclohexyl]-4-[[(7R)-7-ethyl-5,6,7,8-tetrahydro-5-methyl-8-(1-methylethyl)-6-oxo-2-pteridinyl]amino]-3-methoxy-, hydrochloride (1:3)
Preferred Name English
VOLASERTIB HYDROCHLORIDE [JAN]
Common Name English
BI 6727 trihydrochloride
Code English
BI 6727 CL3
Code English
VOLASERTIB TRIHYDROCHLORIDE [USAN]
Common Name English
Volasertib trihydrochloride [WHO-DD]
Common Name English
BI-6727-CL3
Code English
BI-6727 CL3
Code English
Classification Tree Code System Code
NCI_THESAURUS C1404
Created by admin on Wed Apr 02 18:29:56 GMT 2025 , Edited by admin on Wed Apr 02 18:29:56 GMT 2025
NCI_THESAURUS C129825
Created by admin on Wed Apr 02 18:29:56 GMT 2025 , Edited by admin on Wed Apr 02 18:29:56 GMT 2025
Code System Code Type Description
SMS_ID
300000013049
Created by admin on Wed Apr 02 18:29:56 GMT 2025 , Edited by admin on Wed Apr 02 18:29:56 GMT 2025
PRIMARY
FDA UNII
O72812O5MN
Created by admin on Wed Apr 02 18:29:56 GMT 2025 , Edited by admin on Wed Apr 02 18:29:56 GMT 2025
PRIMARY
USAN
YY-65
Created by admin on Wed Apr 02 18:29:56 GMT 2025 , Edited by admin on Wed Apr 02 18:29:56 GMT 2025
PRIMARY
CAS
946161-17-7
Created by admin on Wed Apr 02 18:29:56 GMT 2025 , Edited by admin on Wed Apr 02 18:29:56 GMT 2025
PRIMARY
PUBCHEM
16718566
Created by admin on Wed Apr 02 18:29:56 GMT 2025 , Edited by admin on Wed Apr 02 18:29:56 GMT 2025
PRIMARY
NCI_THESAURUS
C152906
Created by admin on Wed Apr 02 18:29:56 GMT 2025 , Edited by admin on Wed Apr 02 18:29:56 GMT 2025
PRIMARY
DRUG BANK
DBSALT002905
Created by admin on Wed Apr 02 18:29:56 GMT 2025 , Edited by admin on Wed Apr 02 18:29:56 GMT 2025
PRIMARY
ChEMBL
CHEMBL1233528
Created by admin on Wed Apr 02 18:29:56 GMT 2025 , Edited by admin on Wed Apr 02 18:29:56 GMT 2025
PRIMARY
Related Record Type Details
Structure of Volasertib
PARENT -> SALT/SOLVATE
Structure of Volasertib trihydrochloride trihydrate
ANHYDROUS->SOLVATE
Related Record Type Details
Structure of Volasertib
ACTIVE MOIETY
NIH
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