Onalespib

Protein target name:

HSP90

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

100 nM

Probe Availability

MedChemExpress

Selleck Chemicals

Probe Information

Target and Probe Information

Target Details

Target class:

EL52; HSPN; LAP2; HSP86; HSPC1; HSPCA; Hsp89; Hsp90; LAP-2; HSP89A; HSP90A; HSP90N; Hsp103; HSPCAL1; HSPCAL4; HEL-S-65p; HSP84; HSPC2; HSPCB; D6S182; HSP90B

Probe Details

Chemical Probes Portal ID:

CPP2148

Probe alias:

cpd 35, A13387, XJX

PubChem CID:

11955716

ChEMBL ID:

CHEMBL1214827

SMILES string:

OC1=CC(O)=C(C(C)C)C=C1C(N2CC(C=CC(CN3CCN(C)CC3)=C4)=C4C2)=O

InChi Key:

IFRGXKKQHBVPCQ-UHFFFAOYSA-N

Orthogonal probe:

BIIB021Luminespib

Physico-chemical properties

NMR:

1H NMR (Me-d3-OD) δ 7.37-7.23 (br s, 3H), 7.19 (s, 1H), 6.39 (s, 1H), 4.94-4.87 (br s, 4H), 3.57 (s, 2H), 3.27-3.16 (m, 1H), 2.67-2.39 (m, 8H), 2.31 (s, 3H), 1.23 (d, 6H).

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

0.71 nM

Potency assay:

ITC

PDB ID for probe-target interaction (3D structure):

2XJX

Structure-activity relationship:

yes

Off target activity

Probe Selectivity in Vitro:

hERG inhibition 7% @ 3 uM, 42 % @ 30 uM, Clean profile against the major cytochrome P450 isoforms (≤40% inhibition at 10 μM for 1A2, 2D6, 3A4, 2C9, 2C19)

In cell validation

On target activity in cells

Potency in cells:

IC50, GI50

48 nM, 13-480 nM (GI50)

Potency assay (cells):

Cell Proliferation, expression Inhibition for the oncogenic client proteins Raf-1 and CDK4 (WB) GI50s measured in a panel of 32 human tumor cell lines

In vivo validation

Organism:

Mouse

Dose:

2-60 mg/Kg

Route of delivery:

Intravenous

Plasma half life:

0.9-3.2 h

Systemic clearance:

113-200 mL/min/Kg

Fraction of probe bound to plasma protein:

91 %

Primary Reference

Reference (doi):

10.1021/jm100060b 10.1111/j.1349-7006.2011.02191.x

Reference (PMID):

20662534 22181674

Onalespib

Probe Availability

Probe Information

Target Details

EL52; HSPN; LAP2; HSP86; HSPC1; HSPCA; Hsp89; Hsp90; LAP-2; HSP89A; HSP90A; HSP90N; Hsp103; HSPCAL1; HSPCAL4; HEL-S-65p; HSP84; HSPC2; HSPCB; D6S182; HSP90B

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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Onalespib

Probe Availability

Probe Information

Target Details

EL52; HSPN; LAP2; HSP86; HSPC1; HSPCA; Hsp89; Hsp90; LAP-2; HSP89A; HSP90A; HSP90N; Hsp103; HSPCAL1; HSPCAL4; HEL-S-65p; HSP84; HSPC2; HSPCB; D6S182; HSP90B

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?