CBPD-268

CBPD-268 : Degrader (PROTAC) of CREBBP and EP300

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(1 ratings)

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Probe CBPD-268 is in the process of SERP review.

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Information

CREBBP
EP300

Degrader (PROTAC)

up to 10 nM

In Vitro Validations

Uniprot ID: Q92793

Target Class: Epigenetic

Target SubClass: Bromodomain

Potency: IC50

Potency Value: 11 nM

Potency Assay: Fluorescence Polarization (FP) assay

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

Target aliases:

CREB-binding protein, CBP, CREBBP, CBP_HUMAN, Prot ...

DOI Reference: 10.1021/acs.jmedchem.3c02124

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency assay, off target (cells): To investigate the degradation selectivity of CBPD-268 on a global level in an unbiased manner, a proteomic analysis of CBPD-268 in the VCaP cell line was performed with 1 nM of CBPD-268 for 4 h.

Probe Selectivity in Cell:

CBPD-268 showed a profound and significant depletion of CBP/p300 proteins, with the CBP and p300 protein levels reduced by 75% and 69%, respectively. Several other proteins, including NKX3-1, ZFYVE19, BUB1B, OXLD1, USHBP1, and BRD2, were also reduced moderately. NKX3-1 is an AR target gene, and its expression is coregulated by CBP/p300. GSPT1, one of the previously reported neo-substrates for CRBN based PROTAC degrader, was not reduced by CBPD-268 in the proteomic study, which was further confirmed by Western blotting analysis.

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

The compound appears to be active in a single cell line at an IC50 of 11 nM. However, as a degrader, total protein loss is seen at much lower doses, so this dosing feels sensible for the proposed MoA. Mouse data are interesting, but half lives in plasma, blood and cell media are short, likely requiring repeat dosing for maximal effect, increasing animal distress. A more stable probe would be preferable, and some optimisation may yield a more satisfactory probe compound. However, given the durable impact on target protein levels, this is probably acceptable.

(last updated: 23 Dec 2025 )