BI-2536

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C28H39N7O3
Molecular Weight	521.6544
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC[C@H]1N(C2CCCC2)C3=NC(NC4=CC=C(C=C4OC)C(=O)NC5CCN(C)CC5)=NC=C3N(C)C1=O

InChI

InChIKey=XQVVPGYIWAGRNI-JOCHJYFZSA-N

InChI=1S/C28H39N7O3/c1-5-22-27(37)34(3)23-17-29-28(32-25(23)35(22)20-8-6-7-9-20)31-21-11-10-18(16-24(21)38-4)26(36)30-19-12-14-33(2)15-13-19/h10-11,16-17,19-20,22H,5-9,12-15H2,1-4H3,(H,30,36)(H,29,31,32)/t22-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C28H39N7O3
Molecular Weight	521.6544
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/17291758
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800025301

BI-2536, an inhibitor of Polo-like kinase 1 (Plk-1) was being investigated by Boehringer Ingelheim as a possible treatment for cancer. BI-2536 inhibits Plk1 enzyme activity at low nanomolar concentrations. The compound potently causes a mitotic arrest and induces apoptosis in human cancer cell lines of diverse tissue origin and oncogenome signature. BI-2536 inhibits growth of human tumor xenografts in nude mice and induces regression of large tumors with well-tolerated intravenous dose regimens. In treated tumors, cells arrest in prometaphase, accumulate phosphohistone H3, and contain aberrant mitotic spindles. This mitotic arrest is followed by a surge in apoptosis, detectable by immunohistochemistry and noninvasive optical and magnetic resonance imaging. For addressing the therapeutic potential of Plk1 inhibition, BI-2536 has progressed into clinical studies in patients with locally advanced or metastatic cancers. It underwent phase II clinical studies for the treatment of breast cancer; non-small cell lung cancer; pancreatic cancer; prostate cancer; small cell lung cancer, but these studies were discontinued later.

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/17291758	Inhibitor 8297		0.83 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Acute myeloid leukemia 136 Sources: https://clinicaltrials.gov/ct2/show/NCT00701766	Primary	Phase II 1132	Unknown Approved Use Unknown
Non small cell lung cancer 7 Sources: https://clinicaltrials.gov/ct2/show/NCT00376623	Primary	Phase II 1132	Unknown Approved Use Unknown
Prostate cancer 178 Sources: https://clinicaltrials.gov/ct2/show/NCT00706498	Primary	Phase II 1132	Unknown Approved Use Unknown
Small-cell lung cancer 41 Sources: https://clinicaltrials.gov/ct2/show/NCT00412880	Primary	Phase II 1132	Unknown Approved Use Unknown
Pancreatic cancer 97 Sources: https://clinicaltrials.gov/ct2/show/NCT00710710	Primary	Phase II 1132	Unknown Approved Use Unknown
Solid tumors 145 Sources: https://clinicaltrials.gov/ct2/show/NCT00526149	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
1370 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22658814	300 mg 1 times / 3 weeks multiple, intravenous dose: 300 mg route of administration: Intravenous experiment type: MULTIPLE co-administered: PEMETREXED	PEMETREXED	BI-2536 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1250 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22658814	325 mg 1 times / 3 weeks multiple, intravenous dose: 325 mg route of administration: Intravenous experiment type: MULTIPLE co-administered: PEMETREXED	PEMETREXED	BI-2536 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
840 mg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18955456	200 mg single, intravenous dose: 200 mg route of administration: Intravenous experiment type: SINGLE co-administered:		BI-2536 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
921 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18955456	250 mg single, intravenous dose: 250 mg route of administration: Intravenous experiment type: SINGLE co-administered:		BI-2536 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
3920 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22658814	300 mg 1 times / 3 weeks multiple, intravenous dose: 300 mg route of administration: Intravenous experiment type: MULTIPLE co-administered: PEMETREXED	PEMETREXED	BI-2536 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4120 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22658814	325 mg 1 times / 3 weeks multiple, intravenous dose: 325 mg route of administration: Intravenous experiment type: MULTIPLE co-administered: PEMETREXED	PEMETREXED	BI-2536 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2480 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18955456	200 mg single, intravenous dose: 200 mg route of administration: Intravenous experiment type: SINGLE co-administered:		BI-2536 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3100 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18955456	250 mg single, intravenous dose: 250 mg route of administration: Intravenous experiment type: SINGLE co-administered:		BI-2536 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
36.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22658814	300 mg 1 times / 3 weeks multiple, intravenous dose: 300 mg route of administration: Intravenous experiment type: MULTIPLE co-administered: PEMETREXED	PEMETREXED	BI-2536 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
32.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22658814	325 mg 1 times / 3 weeks multiple, intravenous dose: 325 mg route of administration: Intravenous experiment type: MULTIPLE co-administered: PEMETREXED	PEMETREXED	BI-2536 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
15.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18955456	200 mg single, intravenous dose: 200 mg route of administration: Intravenous experiment type: SINGLE co-administered:		BI-2536 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
15.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/18955456	250 mg single, intravenous dose: 250 mg route of administration: Intravenous experiment type: SINGLE co-administered:		BI-2536 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY116203	https://www.001chemical.com/chem/search?q=DY116203
1PlusChem LLC	1P00G31Y	https://www.1pchem.com/search?query=1P00G31Y
AChemBlock	10293	http://www.achemblock.com/catalogsearch/result/?q=10293
AK Scientific	SYN1019	https://aksci.com/item_detail.php?cat=SYN1019
AK Scientific	X7373	https://aksci.com/item_detail.php?cat=X7373
AOBIOUS INC	AOB1365	http://aobious.com/aobious/search?search_query=AOB1365
Alfa Chemistry	ACM755038029	http://www.alfa-chemistry.com/search.aspx?q=ACM755038029
Ambeed	A203461	http://www.ambeed.com/search/Search.html?keyword=A203461
ApexBio Technology	A3965	https://www.apexbt.com/catalogsearch/result/?q=A3965
AstaTech	29868	http://astatechinc.com/CPSResult.php?CRNO=29868
Axon MedChem	1129	https://www.axonmedchem.com/product/1129
BOC Sciences	755038-02-9	http://www.bocsci.com/description.asp?cas=755038-02-9
Capot Chemical	22397	https://www.capotchem.com/search.do?q=22397
Cayman Chemical	17385	http://www.caymanchem.com/app/template/Product.vm/catalog/17385
Chem Scene	CS-0071	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0071
ChemShuttle	112434	https://www.chemshuttle.com/catalogsearch/result/?q=112434
Hairui	HR113656	http://www.hairuichem.com/en/product/search.do?q=HR113656
KeyOrganics	AS-16191	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16191
Lab Seeker	SC-94632	http://www.labseeker.com/search.php?keywords=SC-94632&category=0
LabSeeker	SC-94632	http://www.labseeker.com/search.php?keywords=SC-94632&category=0
Matrix Scientific	132635	http://www.matrixscientific.com/132635.html
MedChem Express	HY-50698	https://www.medchemexpress.com/search.html?q=HY-50698&ft=&fa=&fp=
MolPort	MolPort-009-679-384	https://www.molport.com/shop/molecule-link/MolPort-009-679-384
Molcore	MC116203	http://www.molcore.com/CatMC116203.html
Molnova	M15870	https://www.molnova.com/en/serch-list.html?keywords=M15870
MuseChem	I004792	https://www.musechem.com/product/I004792.html
ShangHai Biochempartner	BCP000082	http://www.biochempartner.com/search_BCP000082
TargetMol	T6173	https://www.targetmol.com/search?keyword=T6173
Toronto Research Chemicals	B373470	https://www.trc-canada.com/product-detail/?CatNum=B373470
eMolecules	108759452	https://orderbb.emolecules.com/search/#?query=108759452
eMolecules	300442060	https://orderbb.emolecules.com/search/#?query=300442060
eMolecules	31507631	https://orderbb.emolecules.com/search/#?query=31507631
eNovation Chemicals	K31318	https://www.enovationchem.com/Products.asp?SEARCHTEXT=K31318&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-1845539356	https://mcule.com/MCULE-1845539356/
mcule	MCULE-3299098489	https://mcule.com/MCULE-3299098489/

PubMed

Title	Date	PubMed
		252159885
BI 2536, a potent and selective inhibitor of polo-like kinase 1, inhibits tumor growth in vivo.	2007 Feb 20	17291758
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.	2010 Nov 24	21095574
Comprehensive analysis of kinase inhibitor selectivity.	2011 Oct 30	22037378
Hit to Lead optimization of a novel class of squarate-containing polo-like kinases inhibitors.	2012 Dec 15	23103095
BRD4 associates with p53 in DNMT3A-mutated leukemia cells and is implicated in apoptosis by the bromodomain inhibitor JQ1.	2013 Dec	24403256
Dual kinase-bromodomain inhibitors for rationally designed polypharmacology.	2014 Apr	24584101

Patents

Sample Use Guides

In Vivo Use Guide

200 mg of i.v. BI- 2536, administered once every 3 weeks in patients with advanced metastatic hormone-refractory prostate cancer

Route of Administration: Intravenous

In Vitro Use Guide

BI-2536 treatment ranging from 10-100 nM leads to the blocking of the recruitment of γ-tubulin and phosphorylation of Apc6 at mitotic centrosomes, inhibition of cohesin release from chromosome arms, induction of monopolar spindles, as well as a range of other mitotic processes, dependent on Plk1 in HeLa cultures.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:11:44 GMT 2023` Edited by `admin` on `Fri Dec 15 15:11:44 GMT 2023`
Record UNII	4LJG22T9C6
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

BI-2536

Code

English

(R)-4-((8-CYCLOPENTYL-7-ETHYL-5,6,7,8-TETRAHYDRO-5-METHYL-6-OXO-2-PTERIDINYL)AMINO)-3-METHOXY-N-(1-METHYL-4-PIPERIDINYL)BENZAMIDE

Systematic Name

English

BENZAMIDE, 4-(((7R)-8-CYCLOPENTYL-7-ETHYL-5,6,7,8-TETRAHYDRO-5-METHYL-6-OXO-2-PTERIDINYL)AMINO)-3-METHOXY-N-(1-METHYL-4-PIPERIDINYL)-

Systematic Name

English

BI2536

Code

English

BI 2536 [WHO-DD]

Common Name

English

Code System Code Type Description

ChEMBL

CHEMBL513909