NVS-BPTF-1

NVS-BPTF-1 : Inhibitor of BPTF

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(0 ratings)

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Probe NVS-BPTF-1 is in the process of SERP review.

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Information

BPTF

Inhibitor

up to 1 uM

Additional Data

SGC Chemical Probe Collection

Probe Availability:

MCULE

In Vitro Validations

Uniprot ID: Q12830

Target Class: Epigenetic

Target SubClass: Bromodomain

Potency: Kd

Potency Value: 3 nM

Potency Assay: BROMOscan

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

Target aliases:

Nucleosome-remodeling factor subunit BPTF, FALZ, F ...

DOI Reference: 10.1016/j.bmcl.2021.128208

Uniprot ID: Q12830

Target Class: Epigenetic

Target SubClass: Bromodomain

Potency: Kd

Potency Value: 71 nM

Potency Assay: BLI assay

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

Target aliases:

Nucleosome-remodeling factor subunit BPTF, FALZ, F ...

DOI Reference: 10.1016/j.bmcl.2021.128208

Uniprot ID: Q12830

Target Class: Epigenetic

Target SubClass: Bromodomain

Potency: IC50

Potency Value: 56 nM

Potency Assay: Alphascreen

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

Target aliases:

Nucleosome-remodeling factor subunit BPTF, FALZ, F ...

DOI Reference: 10.1016/j.bmcl.2021.128208

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Probe Selectivity in Vitro:

A DSF screen against Human bromodomains reveals no significant off-targets. A BROMOscan with NVS-BPTF-1 similarly showed good selectivity. BPTF exhibited a KD of 3nM, BRPF 37nM, CECR2 66nM, GCN5L2 62nM and PCAF 74nM in BROMOscan. NVS-BPTF-1 was also tested against the NIBR principal panel which showed no binding to 12 GPCRs, 3 nuclear receptors, 3 transporters and 7 other enzymes with an IC50<10µM. Against the NIBR kinase panel, NVS-BPTF-1 showed no binding against 48 kinases with an IC50>30µM.

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

The reported IC50 values for NVS-BPTF-1 are single and double digit nM against the primary target (depending upon the assay). The reported off-target potencies for NVS-BPTF-1 against 3 GPCRS are: Ad3 (4.9 uM). D3 (3.5 uM). H3 (4 uM). Therefore, using 1uM NVS-BPTF-1 may be too high a concentration in cells as the results may be due to unknown GPCR or other target polypharmacology. The current recommended cellular concentration is up to 1 uM. 0.5 uM might be more appropriate in order to get a balance between primary target potency (7x BLI assay potency) and off-target potencies D3 (1/7 D3 potency). NVS-BPTF-1 should undergo full GCPR selectivity profiling.

(last updated: 9 May 2022 )

SERP Ratings

In Cell Rating

SERP Comments:

NVS-BPTF-1 shows IC50 values for target engagement in the 30-70 nM range and good selectivity in bromodomain and kinase panels. Currently, only limited data is for intracellular target engagement, but a nano-BRET assay with an EC50 of 16 nM for BPTF suggests equal potency in cell-based systems. The compound is reported not to be suitable for in vivo work based on its ADME properties.

(last updated: 14 Jul 2022 )