PROTAC CBP/p300/BRD4 degrader-1 (29c) showed strong antiproliferative activity against PC-3 cells (IC50=2.80 nM), DU145 cells (IC50=6.62 nM), 22Rv1 cells (IC50=16.02 nM) and RM-1 cells (IC50=145.00 nM); it showed low cytotoxicity against normal human prostate epithelial RWPE-1 cells (IC50=4.38 μM), a selectivity index (SI) of >1500 for PC-3/RWPE-1, a selectivity index (SI) of >600 for DU145/RWPE-1, and nanomolar level antiproliferative activity against various colorectal cancer cell lines [1]. PROTAC CBP/p300/BRD4 degrader-1 (30 min to 2 h) showed inhibitory activity against BRD4 (BD1), BRD4 (BD2), p300 and CBP in in vitro biochemical assays, with IC50 values of 44.6 nM, 13.1 nM, 102.6 nM and 110.8 nM, respectively [1]. PROTAC CBP/p300/BRD4 degrader-1 has a strong binding affinity to CRBN, with a Kd value of 3.24 μM [1]. PROTAC CBP/p300/BRD4 degrader-1 (24 h, 48 h, 72 h, 96 h) showed time-dependent antiproliferative activity against PC-3 cells [1]. PROTAC CBP/p300/BRD4 degrader-1 (used in combination with paclitaxel at dose ratios of 1:2 and 1:3) showed synergistic antiproliferative effects with paclitaxel in PC-3 cells, with IC50 values of 5.59 nM (1:2) and 7.83 nM (1:3), respectively[1]. PROTAC CBP/p300/BRD4 degrader-1 (0.1 nM-1000 nM; 12 h, 24 h) degraded BRD4, CBP and p300 in PC-3, DU145 and RM-1 cells in a concentration-dependent manner. In PC-3 cells, the DC50 value of BRD4 was 8.8 pM, the DC50 value of CBP was 6.55 nM and the DC50 value of p300 was 1.05 nM; it degraded in a time-dependent manner[1]. PROTAC CBP/p300/BRD4 degrader-1 (1 nM, 24 hours) downregulated the expression of c-Myc and Ac-H3K27 and degraded BRD2 and BRD3 in PC-3 cells via a hook effect [1]. PROTAC CBP/p300/BRD4 degrader-1 (30 nM; BRD4 degradation for 12 hours, CBP/p300 degradation for 24 hours) degraded BRD4 and CBP/p300 in PC-3 cells, and the degradation was reversible, with protein levels recovering within 48 hours after elution of the compound [1]. PROTAC CBP/p300/BRD4 degrader-1 (BRD4 concentration of 1.0 nM, CBP/p300 concentration of 30 nM; BRD4 treatment for 12 hours, CBP/p300 treatment for 24 hours) degrades BRD4 and CBP/p300 in PC-3 cells in a CRBN and proteasome-dependent manner [1]. PROTAC CBP/p300/BRD4 degrader-1 (BRD4 concentration of 1.0 nM, CBP/p300 concentration of 30 nM; BRD4 treatment for 6 hours, CBP/p300 treatment for 12 hours) requires the formation of a ternary complex to degrade BRD4 and CBP/p300 in PC-3 cells, and this degradation is attenuated by pretreatment with thalidomide (10.0 μM) or cotreatment with NEO2734 (10.0 μM) [1].

PROTAC CBP/p300/BRD4 degrader-1 (29c) (0.1-0.2 mg/kg; intraperitoneal injection; every other day; 24 days) showed potent dose-dependent antitumor activity in the PC-3 prostate cancer xenograft model, achieving a tumor growth inhibition rate of 81.5% at a dose of 0.2 mg/kg, and exhibiting good safety [1].

Animal/Disease Models:NOD-SCID (male, 6-week-old, PC-3 human prostate cancer cell xenograft model) [1]
Doses: 0.1 mg/kg; 0.2 mg/kg
Route of Administration: Intraperitoneal injection; every other day; for 24 days
Experimental Results: The tumor growth inhibition rate (TGI) at the 0.1 mg/kg dose was 55.6%. The TGI at the 0.2 mg/kg dose was 81.5%, which was significantly better than the positive control drugs NEO2734 (TGI of 67.9% at 20 mg/kg dose) and paclitaxel (TGI of 64.1% at 5 mg/kg dose). The dose-dependent degradation of CBP, p300 and BRD4 was confirmed by immunohistochemical staining of tumor tissue. TUNEL staining showed that apoptosis was significantly increased in the treatment group, which was higher than that in the NEO2734 or paclitaxel group. H&E staining showed no obvious histopathological abnormalities in the major organs (liver, heart, spleen, lungs, and kidneys), and routine blood tests also did not reveal significant changes in organ function indicators.

[1]. Discovery of Novel CBP/p300 and BRD4 Dual-Target PROTACs with Potent Antitumor Activity in Prostate Cancer. J Med Chem. 2026;69(4):4512-4547.

C41H42F3N7O7

801.81

3109024-12-3

Typically exists as solids at room temperature

O=C1N(C(C2=C1C=CC(N3CCC(CC3)C(N4CCC(CC4)C5=NC6=CC=C(C=C6N5CCOC(F)(F)F)C(C=C7C)=CN(C7=O)C)=O)=C2)=O)C(C(N8)=O)CCC8=O

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)