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Luminespib | Inhibitor of HSP90AA1, HSP90AB1
RATINGS:
Cellular Use: (3 reviews)

In Model Organisms: (3 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
HSP90AA1
  • IC50:7.8 nM
  • GI50* :from 2.3 to 39 nM in various tumour cells; (*Growth Inhibition 50%)
HSP90AB1
  • IC50:21 nM
  • GI50* :from 2.3 to 39 nM in various tumour cells; (*Growth Inhibition 50%)
Inhibitor
up to 1 uM

Selectivity

In Vitro Selectivity Assessment

Potency: IC50 - GRP94 535 nM, TRAP-1 85 nM

Potency Assay Off-Target:
Fluorescence polarisation (FP) competitive binding assay
Selectivity Assessment Description:
At 10 uM there is no inhibition of human HSP72 ATPase or decatenation activity of human topoisomeras ...

Potency
Cellular
In Vitro

HSP90AA1

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? No

DOI Reference: 10.1158/1078-0432.CCR-05-0518

HSP90AB1

Mode of Action: Inhibitor

Structure-Activity-Relationship data available? No

DOI Reference: 10.1158/1078-0432.CCR-05-0518

In Vivo Validations

Mouse
Dose: 50 mg/Kg
Route of delivery: Intraperitoneal, Intravenous
Plasma half life: 15 h in Tumor, 2 h in Plasma
Systemic clearance: 0.143 L/h in Plasma 0.020 L/h in Tumor
Target engagement assay: Therapeutic activity was tested in established human xenografts (colon, glioblastoma, breast, ovarian, and prostate) providing evidence of antitumour activity. Evidence of HSP90 inhibition comes from changes in the biomarkers as reported in Banerji et al 2005 (DOI: 10.1158/1078-0432.CCR-05-0518)

DOI Reference: 10.1158/1078-0432.CCR-05-0518

Orthogonal Probes def

ONALESPIB
BIIB021

Chemical Information

Molecular Formula C26H31N3O5
SMILEs CCNC(=O)c1noc(-c2cc(C(C)C)c(O)cc2O)c1-c1ccc(CN2CCOCC2)cc1
InChI InChI=1S/C26H31N3O5/c1-4-27-26(32)24-23(18-7-5-17(6-8-18)15-29-9-11-33-12-10-29)25(34-28-24)20-13-19(16(2)3)21(30)14-22(20)31/h5-8,13-14,16,30-31H,4,9-12,15H2,1-3H3,(H,27,32)
Molecular weight 465.23 Da
AlogP 0.0
HBond acceptors 8
HBond donors 3
Atoms 65

Vendors

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Expert Reviews

by SERP
(on 3 Jul 2020 )
Cellular Use Rating
In Model Organisms
AUY922 targets members of the heat shock protein 90 (Hsp90) family. This molecule binds to the N-terminal nucleotide-binding sites of Hsp90s. It is worth noting that there are other possible binding...
by SERP
(on 5 Sept 2020 )
Cellular Use Rating
In Model Organisms
( The reviewer did not leave any comments )
by SERP
(on 10 Nov 2020 )
Cellular Use Rating
In Model Organisms
( The reviewer did not leave any comments )
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