BI-3802

Protein target name:

BCL6

Mechanism of action:

Degrader

Recommended Concentration for use in cells:

~~up to 1 uM~~

Reviewer suggested Concentration for use in cells:

up to 5 uM

Probe Availability

MedChemExpress

Probe Information

Target and Probe Information

Target Details

Target class:

Transcription factor

Subclass:

Transcriptional Repressor

HUGO ID:

HGNC:1001

Entrez gene ID:

604

UNIPROT ID:

P41182

Target alias:

BCL5; LAZ3; BCL6A; ZNF51; ZBTB27

Probe Details

Chemical Probes Portal ID:

CPP2198

PubChem CID:

131632978

SMILES string:

ClC1=CN=C(N2C[C@H](C)C[C@H](C)C2)N=C1NC3=CC(C=C(OCC(NC)=O)C(N4C)=O)=C4C=C3

InChi Key:

GXTJETQFYHZHNB-GASCZTMLSA-N

Control compound:

BI-5273

Orthogonal probe:

BI-3812

Physico-chemical properties

NMR:

1H NMR (500 MHz, DMSO-d6): δ 8.90 (s, 1H), 7.98-8.09 (m, 2H), 7.94 (d, J = 2.5 Hz, 1H), 7.73 (dd, J = 2.5, 9.1 Hz, 1H), 7.47 (d, J = 9.1 Hz, 1H), 7.16 (s, 1H), 4.53 (s, 2H), 4.46 (brd, J = 11.0 Hz, 2H), 3.68 (s, 3H), 2.67 (d, J = 4.7 Hz, 3H), 2.28 (t, J = 12.1 Hz, 2H), 1.76 (brd, J = 12.6 Hz, 1H), 1.44-1.60 (m, 2H), 0.85 (d, J = 6.6 Hz, 6H), 0.77 (q, J = 12.2 Hz, 1H);

13C NMR (100 MHz, DMSO-d6): δ 167.2, 158.9, 157.2, 155.8, 154.5, 147.1, 134.1, 132.2, 123.4, 120.6, 119.9, 114.7, 113.6, 102.0, 68.3, 51.4, 42.5, 30.9, 30.2, 25.9, 19.6;

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

≤ 3 nM

Potency assay:

BCL6::BCOR Ulight TR-FRET

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

5MW2, 6XMX

Structure-activity relationship:

yes

Off target activity

Probe Selectivity in Vitro:

Safety Screen 44 for GPCR and Invitrogen Kinase panel shows no inhibition, Whole-proteome quantification of SuDHL4Cas9 cells treated with 1 μM BI-3802 shows no other protein degradation.

In cell validation

On target activity in cells

Potency in cells:

IC50,DC50, Dmax

20 nM DC50, 43 nM IC50, 80% Dmax

Potency assay (cells):

BCL6::NCOR LUMIER, Antiproliferative assay, western blot of BCL6 in(Farage cells) capillary electrophoresis measuring BCL6 levels in DLBCL cell lines

Mechanistic Control Experiment:

Inactive analogue BI-5273 does not induce degradation. Degradation is proteasome dependent

Phenotypic Control Experiment:

Non-cullin E3 ubiquitin ligase SIAH1degradation assessed by genome-scale CRISPR–Cas9 genetic screens.

In vivo validation

Organism:

Mouse

Dose:

10 mg/Kg, 100 mg/Kg

Route of delivery:

Oral

Cmax:

193 nM @ 10 mg/Kg, 599 nM @ 100 mg/Kg

Primary Reference

Reference (doi):

10.1016/j.celrep.2017.08.081 10.1038/s41586-020-2925-1

Reference (PMID):

28930682 33208943

External Resources

Available data:

OpenMe

BI-3802

Probe Availability

Probe Information

Target Details

BCL5; LAZ3; BCL6A; ZNF51; ZBTB27

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

External Resources

Supporting Organizations

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BI-3802

Probe Availability

Probe Information

Target Details

BCL5; LAZ3; BCL6A; ZNF51; ZBTB27

Probe Details

Physico-chemical properties

In vitro validation

In cell validation

In vivo validation

Primary Reference

External Resources

Supporting Organizations

Interested in supporting the portal?