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
SMILES
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=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
DescriptionSources: http://adisinsight.springer.com/drugs/800026979Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/19383823
Sources: http://adisinsight.springer.com/drugs/800026979
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24204733 | https://www.ncbi.nlm.nih.gov/pubmed/23956067
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
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3024 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19383823 |
0.87 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Doses
Dose | Population | Adverse 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: 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: Page: p.182 |
DLT: Thrombocytopenia, Neutropenia... Dose limiting toxicities: Thrombocytopenia (grade 4, 100%) Sources: Page: p.182Neutropenia (grade 4, 100%) |
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: 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: 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: 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: Page: p.182 |
DLT: Neutropenia, Febrile neutropenia... Disc. AE: Neutropenia... Dose limiting toxicities: Neutropenia (grade 3, 10%) AEs leading toFebrile neutropenia (grade 4, 20%) Thrombocytopenia (grade 4, 20%) Neutropenia (grade 4, 30%) discontinuation/dose reduction: Neutropenia (10%) Sources: 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: 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: Page: p.182 |
DLT: Neutropenia, Neutropenia... Dose limiting toxicities: Neutropenia (grade 4, 6.8%) Sources: Page: p.182Neutropenia (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%) |
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: 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: Page: p.4 |
DLT: Neutropenia, Thrombocytopenia... Dose limiting toxicities: Neutropenia (grade 4, 33.3%) Sources: Page: p.4Thrombocytopenia (grade 4, 33.3%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: Page: p.4 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26627079
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26851014
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).
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C1404
Created by
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NCI_THESAURUS |
C129825
Created by
admin on Sat Dec 16 20:11:06 GMT 2023 , Edited by admin on Sat Dec 16 20:11:06 GMT 2023
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300000013049
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O72812O5MN
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YY-65
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946161-17-7
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16718566
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C152906
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DBSALT002905
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CHEMBL1233528
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ACTIVE MOIETY
SUBSTANCE RECORD