General
Preferred name
BI 2536
Synonyms
BI-2536 ()
KIN001-124 ()
BI2536 ()
NPK33-1-98-1 ()
Bi 2536 ()
P&D ID
PD003376
CAS
755038-02-9
Tags
available
free of charge
probe
drug candidate
Drug indication
Acute myeloid leukaemia
Neoplasm
Drug Status
investigational
Max Phase
2.0
Probe info
Probe type
calculated probe
experimental probe
Probe sources
Probe targets
[[ compound.targets[t].gene_name ]]
Probe control
Orthogonal probes
65
No orthogonal probes found
Similar probes
12
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
COMMENT
Jun 12 2016 - 3:17am; BI-2356 has been subject to kinome profiling (doi:10.1038/nbt.1990). Although it is active against >20 kinases at 1 uM, it is potent and selective for PLK1, PLK2, and to a lesser extent PLK3 at very low nM doses. CAMKK1/2 and RPS6KA4 (Kin.Dom.2-C-terminal) would be off-targets in the ~20 nM and 12 nM range, respectively. Jun 21 2016 - 12:08pm; BI 2536 given i.v. once or twice per week is highly efficacious in diverse xenograft models with acceptable tolerability by inhibiting cell proliferation through a mitotic arrest, and subsequently induction of tumor-cell death. Administration of BI 2536 at 50 mg/kg once or twice per week significantly inhibits growth of HCT 116 xenografts with T/C of 15% and 0.3%, respectively. BI 2536 treatment twice-weekly also leads to excellent tumor-growth in BxPC-3 and A549 models with T/C of 5% and 14%, respectively. BI 2536 blocks the activities of PLK2 and PLK3 with IC50s of 3.5 nM and 9.0 nM, respectively. In HeLa cells, 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 that are known to depend on PLK1. BI 2536 treatment leads to HeLa cell arrest in G2/M, subsequently a sub-G1 DNA peak indicative of DNA breakdown and apoptosis, and accumulated cleaved PARP p85 fragments in a concentration-dependent manner. BI 2536 inhibits the growth of a panel of 32 human cancer cell lines with EC50s of 2-25 nM, while blocking the proliferation of exponentially growing hTERT-RPE1, human umbilical vein endothelial cells (HUVECs), and normal rat kidney (NRK) cells with EC50s of 12-31 nM. PLK1 inhibition by BI 2536 reduces the growth and viability of anaplastic thyroid carcinoma (ATC) cells such as CAL62, OCUT-1, SW1736, 8505C, and ACT-1 with EC50 values of 1.4-5.6 nM. Jun 23 2016 - 7:25pm; BI2536 is a potent inhibitor of the PLK kinase family (PLK1/2/3 IC50 0.83/3.5/9.0 nM). Its selectivity was excellent in a protein kinase panel of modest size (63 other kinases). PLK4 was not a member of that panel. BI2536 is cell-permeable, causing HeLa cell-cycle block in G2 or mitosis at 10-50 nM and inhibiting a range of other cancer cell proliferation at 1-100 nM EC50. It was effective in a mouse xenograft model intravenously dosed (40-50 mg/kg weekly or bi-weekly). This compound is not a pure PLK chemical probe; it is also a potent inhibitor of the BET family bromodomains (BRD4-BD1 IC50 25 nM by AlphaScreen, Kd 37 nM by ITC, IC50 100 nM vs BRD4 in a FRAP cellular assay) and has a polypharmacological profile (doi:10.1021/cb500072z, doi:10.1038/nchembio.1471) For that reason, I would not choose this compound as a selective probe for the PLK family. Jun 29 2016 - 4:44pm; Mar 3 2020 - 2:03pm; BI2536 is a reasonably selective PLK inhibitor (PLK1/2/3) but BI2536 also targets BET bromodomains (10.1021/acsmedchemlett.5b00084). Despite being a PLK1 inhibitor that induces all the hallmarks of PLK1 inhibition, any observed cellular phenotypes should be interpreted with caution. BI2536 is considered a compound with polypharmacological activity; it has been superseded by Volasertib (BI6727). Mar 12 2020 - 11:57am
DESCRIPTION
BI-2536 was initially reported as a polo-like kinase 1 (PLK1) inhibitor . More recently, this compound has been discovered to function, in addition, as a BRD4 (bromodomain) inhibitor . It is suggested that BI-2536 be termed a dual kinase-bromodomain inhibitor.
(GtoPdb)
DESCRIPTION
BI 2536 is a dual PLK1 and BRD4 inhibitor with IC50s of 0.83 and 25 nM, respectively[1]. BI-2536 suppresses IFNB (encoding IFN-¦Â) gene transcription[4].
PRICE
105
MOA
Inhibitor
(Chemical Probes.org)
DESCRIPTION
BI-2536 inhibits the PLK1 enzyme with an IC50 of 0.8 nM and is active in a large variety of human tumor cell lines in the range of EC50 = 2-25 nM. In vivo, BI-2536 is efficacious in mouse xenograft models in the range of 30-60 mg/kg (once or twice weekly i.v. administration).
(opnMe Portal)
DESCRIPTION
inhibitor of polo-like kinase 1 (PLK1)
(Informer Set)
DESCRIPTION
BI-2563 is a small molecule compound with potential antineoplastic activities. BI 2536 binds to and inhibits Polo-like kinase 1 (Plk1), resulting in mitotic arrest, disruption of cytokinesis, and apoptosis in susceptible tumor cell populations. Plk1, a serine/threonine-protein kinase, is a key regulator of multiple processes fundamental to mitosis and cell division.
(BOC Sciences Bioactive Compounds)
DESCRIPTION
BI 2536 has selectivity for Plk1 over Plk2 and Plk3 with IC50 = 0.51 nM for Plk1. BI-2536 is also an inhibitor of BRD4 with IC50 = 25 nM.
(Enamine Bioactive Compounds)
DESCRIPTION
BI2536 is an effective Plk1 inhibitor (IC50: 0.83 nM). It has 4- and 11-fold greater selectivity than Plk2 and Plk3.
(TargetMol Bioactive Compound Library)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Cell lines
396
Organisms
2
Compound Sets
34
AdooQ Bioactive Compound Library
Axon Medchem Screening Library
BOC Sciences Bioactive Compounds
Cayman Chemical Bioactives
ChEMBL Drugs
Chemical Probes.org
Chemical proteomics reveals the target landscape of 1,000 kinase inhibitors
Clinical kinase drugs
CZ-OPENSCREEN Bioactive Library
Drug Repurposing Hub
DrugBank
DrugMAP
Enamine Bioactive Compounds
EU-OPENSCREEN Bioactive Compound Library
EUbOPEN Chemogenomics Library
Guide to Pharmacology
High-quality chemical probes
Informer Set
JUMP-Target 1 Compound Set
Kinase Chemogenomic Set (KCGS)
Kinase Inhibitors (best-in-class)
LSP-MoA library (Laboratory of Systems Pharmacology)
LSP-OptimalKinase library (Laboratory of Systems Pharmacology)
MedChem Express Bioactive Compound Library
Novartis Chemogenetic Library (NIBR MoA Box)
opnMe Portal
Probe Miner (suitable probes)
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
Tool Compound Set
Welcome Trust Cancer Drugs
ZINC Tool Compounds
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
32
Molecular Weight
521.31
Hydrogen Bond Acceptors
8
Hydrogen Bond Donors
2
Rotatable Bonds
7
Ring Count
5
Aromatic Ring Count
2
cLogP
3.56
TPSA
102.93
Fraction CSP3
0.57
Chiral centers
1.0
Largest ring
6.0
QED
0.57
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
PLK1
PLK1, PLK2, PLK3
PLK1/2/3
Serine/threonine-protein kinase PLK1
Serine/threonine-protein kinase PLK2
Serine/threonine-protein kinase PLK3
Apoptosis
Epigenetic Reader Domain
PLK
PLK2
PLK3
PLK1, PLK2, PLK3, RPS6KA4, CAMKK1, CAMKK2, MYLK
BRD4, PLK1, PLK2, PLK3
PLK1 inhibitor
Polo-like Kinase (PLK)
Apoptosis related,Autophagy,Epigenetic Reader Domain,Myc,PLK
Compound status
clinical
Pathway
mitosis
Cell Cycle/DNA Damage
Epigenetics
Cell Cycle/Checkpoint
Chromatin/Epigenetic
Known off targets
BRD4
Member status
member
MOA
Antimitotic Drugs
Polo-like Kinase-1 (Plk-1) Inhibitors
PLK inhibitor
Target class
Protein kinase
Kinase, Kinase, Kinase
Therapeutic Class
Anticancer Agents
Target subclass
Other, Other, Other
Recommended Cell Concentration
1 uM
Source data
