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Details

Stereochemistry ABSOLUTE
Molecular Formula C34H50N8O3.3ClH.3H2O
Molecular Weight 782.241
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Volasertib trihydrochloride trihydrate

SMILES

O.O.O.Cl.Cl.Cl.CC[C@H]1N(C(C)C)C2=C(C=NC(NC3=CC=C(C=C3OC)C(=O)N[C@H]4CC[C@@H](CC4)N5CCN(CC6CC6)CC5)=N2)N(C)C1=O

InChI

InChIKey=SYHMNJNOZZNDOP-PUJIEXRPSA-N
InChI=1S/C34H50N8O3.3ClH.3H2O/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;3*1H2/t25-,26-,28-;;;;;;/m1....../s1

HIDE SMILES / InChI
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
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 H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
2554
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
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 0.87 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase III
656
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

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
Page: p.182
unhealthy, ADULT
n = 2
Health Status: unhealthy
Condition: cance
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 2
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Page: p.182
DLT: Thrombocytopenia, Neutropenia...
Dose limiting toxicities:
Thrombocytopenia (grade 4, 100%)
Neutropenia (grade 4, 100%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Page: p.182
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
Page: p.4
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/26627079
Page: p.4
Sources:
https://pubmed.ncbi.nlm.nih.gov/26627079
Page: p.4
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
Page: p.182
unhealthy, ADULT
n = 10
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 10
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Page: p.182
DLT: Neutropenia, Febrile neutropenia...
Disc. AE: Neutropenia...
Dose limiting toxicities:
Neutropenia (grade 3, 10%)
Febrile neutropenia (grade 4, 20%)
Thrombocytopenia (grade 4, 20%)
Neutropenia (grade 4, 30%)
AEs leading to
discontinuation/dose reduction:
Neutropenia (10%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Page: p.182
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
Page: p.182
unhealthy, ADULT
n = 29
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 29
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Page: p.182
DLT: Neutropenia, Neutropenia...
Dose limiting toxicities:
Neutropenia (grade 4, 6.8%)
Neutropenia (grade 3, 3.4%)
Thrombocytopenia (grade 4, 6.8%)
Febrile neutropenia (grade 3, 3.4%)
QT interval prolonged (grade 3, 3.4%)
Fatigue (grade 3, 3.4%)
Weight decreased (grade 3, 3.4%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Page: p.182
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
Page: p.4
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/26627079
Page: p.4
DLT: Neutropenia, Thrombocytopenia...
Dose limiting toxicities:
Neutropenia (grade 4, 33.3%)
Thrombocytopenia (grade 4, 33.3%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/26627079
Page: p.4
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
Page: p.182
unhealthy, ADULT
n = 2
Health Status: unhealthy
Condition: cance
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 2
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Page: p.182
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
Page: p.182
unhealthy, ADULT
n = 2
Health Status: unhealthy
Condition: cance
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 2
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Page: p.182
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
Page: p.182
unhealthy, ADULT
n = 10
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 10
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Page: p.182
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
Page: p.182
unhealthy, ADULT
n = 10
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 10
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Page: p.182
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
Page: p.182
unhealthy, ADULT
n = 10
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 10
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Page: p.182
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
Page: p.182
unhealthy, ADULT
n = 10
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 10
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Page: p.182
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
Page: p.182
unhealthy, ADULT
n = 10
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 10
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Page: p.182
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
Page: p.182
unhealthy, ADULT
n = 29
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 29
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Page: p.182
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
Page: p.182
unhealthy, ADULT
n = 29
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 29
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Page: p.182
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
Page: p.182
unhealthy, ADULT
n = 29
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 29
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Page: p.182
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
Page: p.182
unhealthy, ADULT
n = 29
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 29
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Page: p.182
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
Page: p.182
unhealthy, ADULT
n = 29
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 29
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Page: p.182
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
Page: p.182
unhealthy, ADULT
n = 29
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 29
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Page: p.182
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
Page: p.182
unhealthy, ADULT
n = 29
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 29
Sources:
https://pubmed.ncbi.nlm.nih.gov/22119200
Page: p.182
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
Page: p.4
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/26627079
Page: p.4
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
Page: p.4
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/26627079
Page: p.4
Sourcing

Sourcing

Vendor/AggregatorIDURL
AstaTech
42700
http://astatechinc.com/CPSResult.php?CRNO=42700
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
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
PubMed

PubMed

TitleDatePubMed
Polo-like kinases and the orchestration of cell division.
2004 Jun
Use of the novel Plk1 inhibitor ZK-thiazolidinone to elucidate functions of Plk1 in early and late stages of mitosis.
2007 Oct
Polo-like kinase (PLK) inhibitors in preclinical and early clinical development in oncology.
2009 Jun
Hit to Lead optimization of a novel class of squarate-containing polo-like kinases inhibitors.
2012 Dec 15
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 Sat Dec 16 20:11:36 GMT 2023
Edited
by admin
on Sat Dec 16 20:11:36 GMT 2023
Record UNII
UDG4RT6W6J
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
Volasertib trihydrochloride trihydrate
Common 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, hydrate (1:3:3)
Systematic Name English
Code System Code Type Description
CAS
946161-18-8
Created by admin on Sat Dec 16 20:11:36 GMT 2023 , Edited by admin on Sat Dec 16 20:11:36 GMT 2023
PRIMARY
FDA UNII
UDG4RT6W6J
Created by admin on Sat Dec 16 20:11:36 GMT 2023 , Edited by admin on Sat Dec 16 20:11:36 GMT 2023
PRIMARY
Related Record Type Details
Structure of Volasertib
PARENT -> SALT/SOLVATE
Structure of Volasertib Trihydrochloride
SOLVATE->ANHYDROUS
Related Record Type Details
Structure of Volasertib
ACTIVE MOIETY
Structure of Volasertib
ACTIVE MOIETY
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