A-1155463

A-1155463 : BH3 mimetic inhibitor of BCL2L1

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(3 ratings)

note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars.

Information

BCL2L1

BH3 mimetic

50-500 nM

DOI - 10.1021/ml5001867

Probe Availability:

In Vitro Validations

Uniprot ID: Q07817

Target Class: Other

Target SubClass: Apoptosis regulator

Potency: Ki

Potency Value: <0.01 nM

Potency Assay: Time-resolved, flourecence resonance energy transfer (TR-FRET) assays

PDB ID for probe-target interaction (3D structure): 4QVX

Structure-activity relationship: Yes, see PMID: 25313317

Target aliases:

Bcl-2-like protein 1, BCLX, BCL2L, BCL2L1, B2CL1_H ...

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency end-point : Ki BCL2: 80 nM, BCLW: 19 nM, MCL1: >440 nM

Potency assay (off target): TR-FRET assays

I have extra information to add

SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

(last updated: 25 Apr 2017 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

This is a very promising probe.

(last updated: 19 May 2017 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

This probe is a selective picomolar inhibitor of BCL-XL. I recommend to use this probe to interrogate BCL-XL target in cells. It should be used in combination with ABT-199 (a selective inhibitor of BCL-2) to decouple BCL-XL and BCL-2 pathways. One concern, however, is that the molecule binds BCL-W (K_i=19 nM), and yet it inhibits H146 cells in 10% human serum with EC₅₀=65 nM, which is close to K_i for BCL-W. Thus, BCL-W is a potential off target. As for in vivo use, this probe may be used with caution since its tissue and organ distribution were not reported. It does affect platelet counts (dependence on BCL-XL).

(last updated: 12 Jun 2017 )