Volasertib

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C34H50N8O3
Molecular Weight	618.8126
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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=SXNJFOWDRLKDSF-STROYTFGSA-N

InChI=1S/C34H50N8O3/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)/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

Description
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serine/threonine-protein kinase PLK1 14 Target ID: CHEMBL3024 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19383823	Inhibitor 8297		0.87 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Acute myeloid leukemia 136 Sources: http://adisinsight.springer.com/drugs/800026979	Primary	Phase III 656	Unknown Approved Use Unknown
Ovarian cancer 157 Sources: http://adisinsight.springer.com/drugs/800026979	Primary	Phase II 1132	Unknown Approved Use Unknown
Non-small cell lung cancer 206 Sources: http://adisinsight.springer.com/drugs/800026979	Primary	Phase II 1132	Unknown Approved Use Unknown

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: 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

Sourcing

Vendor/Aggregator	ID	URL
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

Title	Date	PubMed
		252160177
Use of the novel Plk1 inhibitor ZK-thiazolidinone to elucidate functions of Plk1 in early and late stages of mitosis.	2007 Oct	17671160
Polo-like kinase (PLK) inhibitors in preclinical and early clinical development in oncology.	2009 Jun	19474163
Hit to Lead optimization of a novel class of squarate-containing polo-like kinases inhibitors.	2012 Dec 15	23103095

Patents

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 `Fri Dec 15 17:25:11 UTC 2023` Edited by `admin` on `Fri Dec 15 17:25:11 UTC 2023`
Record UNII	6EM57086EA
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

Volasertib

Official Name

English

Volasertib [WHO-DD]

Common Name

English

volasertib [INN]

Common Name

English

VOLASERTIB [USAN]

Common Name

English

N-{trans-4-[4-(Cyclopropylmethyl)piperazin-1-yl]cyclohexyl}-4-{[(7R)-7-ethyl-5-methyl-8-(1-methylethyl)-6-oxo-5,6,7,8-tetrahydropteridin-2-yl]amino}-3-methoxybenzamide

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-

Common Name

English

BI6727

Code

English

BI-6727

Code

English

Classification Tree Code System Code

FDA ORPHAN DRUG

415913