| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
CREB Binding Protein (CBP) bromodomain (Ki = 0.5 nM; IC50 for CBP bromodomain binding = 1.5 nM) [1]
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| ln Vitro |
In primary macrophages, PF-CBP1 regulates important inflammatory genes. RGS4 in neurons is a target linked to Parkinson's disease that is downregulated by PF-CBP1. ITC was 105-fold more selective than BRD4, whereas PF-CBP1 was 139-fold more selective in biochemical experiments. As has been seen with other CBP inhibitors, F-CBP1 is likewise a strong inhibitor of EP300 [1].
PF-CBP1 showed high selectivity for CBP bromodomain: no significant binding to other bromodomains (e.g., BRD4, BRD2, BRD3, PCAF) at concentrations up to 10 μM [1] - In HeLa cells, PF-CBP1 (1 μM, 6 h) reduced CBP occupancy at the BCL6 and MYC gene promoters (ChIP-qPCR assay), with ~60% and ~55% reduction respectively compared to DMSO control [1] - PF-CBP1 (0.1-10 μM) dose-dependently inhibited CBP-dependent transcriptional activation: EC50 = 0.3 μM in a luciferase reporter assay (HeLa cells transfected with CBP-responsive promoter) [1] - In diffuse large B-cell lymphoma (DLBCL) cell lines (OCI-LY10, SU-DHL4), PF-CBP1 (1-5 μM, 48 h) reduced BCL6 and MYC mRNA expression (qPCR) by 40%-65% and 35%-50% respectively; corresponding protein levels (western blot) were decreased by 30%-55% and 25%-45% [1] - PF-CBP1 (0.5-10 μM, 72 h) inhibited proliferation of DLBCL cell lines (OCI-LY10, SU-DHL4, SU-DHL6) with IC50 values of 2.3 μM, 3.1 μM, and 4.5 μM respectively (MTT assay) [1] - In OCI-LY10 cells, PF-CBP1 (3 μM, 72 h) induced G1 cell cycle arrest (flow cytometry): G1 phase cells increased from 45% (DMSO) to 68%, S phase cells decreased from 32% to 18% [1] |
| ln Vivo |
In OCI-LY10 DLBCL xenograft mice (female NOD/SCID mice), PF-CBP1 administered orally (50 mg/kg, twice daily) for 21 days significantly inhibited tumor growth: tumor volume at day 21 was 42% of vehicle control (P<0.01); tumor weight at sacrifice was 38% of vehicle control (P<0.01) [1]
- Tumor tissues from PF-CBP1-treated mice showed reduced BCL6 and MYC protein levels (immunohistochemistry) by ~50% and ~45% respectively compared to vehicle [1] - No significant weight loss or gross organ toxicity was observed in PF-CBP1-treated mice during the study [1] |
| Enzyme Assay |
HTRF-based binding assay: Recombinant CBP bromodomain protein was incubated with PF-CBP1 (serial dilutions: 0.001-10 μM) and a fluorescently labeled acetylated histone H4 peptide (H4K5ac/K8ac/K12ac/K16ac). After incubation at room temperature for 1 h, fluorescence resonance energy transfer (FRET) signal was measured. The IC50 value was calculated based on the dose-response curve of signal inhibition [1]
- Surface Plasmon Resonance (SPR) assay: CBP bromodomain protein was immobilized on a sensor chip. PF-CBP1 (serial dilutions: 0.0001-1 μM) was injected over the chip surface at a constant flow rate. Binding affinity (Ki) was determined by fitting the sensorgram data to a 1:1 binding model [1] |
| Cell Assay |
Cell proliferation assay: DLBCL cells were seeded in 96-well plates (5×103 cells/well) and incubated overnight. PF-CBP1 (serial dilutions: 0.1-10 μM) was added, and cells were cultured for 72 h. MTT reagent was added, incubated for 4 h, formazan crystals were dissolved in DMSO, and absorbance was measured at 570 nm. IC50 values were calculated from dose-response curves [1]
- qPCR assay: DLBCL cells were treated with PF-CBP1 (1-5 μM) for 48 h. Total RNA was extracted, reverse-transcribed to cDNA, and qPCR was performed using primers specific for BCL6, MYC, and GAPDH (housekeeping gene). Relative mRNA expression levels were calculated using the ΔΔCt method [1] - Western blot assay: Cells treated with PF-CBP1 (1-5 μM) for 48 h were lysed, proteins were separated by SDS-PAGE, transferred to PVDF membranes, and probed with antibodies against BCL6, MYC, and β-actin (loading control). Immunoreactive bands were visualized by chemiluminescence, and band intensity was quantified by densitometry [1] - ChIP-qPCR assay: HeLa cells treated with PF-CBP1 (1 μM) for 6 h were cross-linked with formaldehyde, lysed, and chromatin was sheared by sonication. CBP-bound chromatin fragments were immunoprecipitated with anti-CBP antibody, cross-links were reversed, and DNA was purified. qPCR was performed using primers targeting the BCL6 and MYC gene promoters to quantify CBP occupancy [1] - Cell cycle analysis: OCI-LY10 cells were treated with PF-CBP1 (3 μM) for 72 h, fixed with ethanol, stained with propidium iodide, and analyzed by flow cytometry. Cell cycle distribution (G1, S, G2/M phases) was determined using flow cytometry software [1] |
| Animal Protocol |
Xenograft model establishment: Female NOD/SCID mice (6-8 weeks old) were subcutaneously injected with 5×106 OCI-LY10 DLBCL cells (suspended in PBS/matrigel) into the right flank. Tumors were allowed to grow to ~100 mm3 before initiating treatment [1]
- Drug administration: Mice were randomly divided into vehicle control group and PF-CBP1 treatment group (n=8/group). PF-CBP1 was dissolved in 10% DMSO + 90% PEG400, and administered orally at a dose of 50 mg/kg, twice daily for 21 consecutive days. Vehicle control mice received the same volume of 10% DMSO + 90% PEG400 [1] - Tumor and body weight monitoring: Tumor volume was measured every 3 days using calipers (volume = length × width² / 2). Body weight was recorded weekly to assess general toxicity [1] - Tissue collection: At the end of treatment, mice were euthanized, tumors were excised, weighed, and divided into portions for immunohistochemistry and protein extraction. Major organs (liver, kidney, spleen) were collected for gross toxicity evaluation [1] |
| ADME/Pharmacokinetics |
Oral bioavailability of PF-CBP1 in mice: 38% (measured by comparing AUC 24 hours after oral and intravenous administration of 10 mg/kg) [1]
- Plasma half-life (t1/2) after oral administration of 50 mg/kg in mice: 4.2 hours [1] - Peak plasma concentration (Cmax) after oral administration of 50 mg/kg in mice: 3.8 μM (reached 1 hour after administration) [1] |
| Toxicity/Toxicokinetics |
Compared with the vector control group, the body weight of mice treated with PF-CBP1 (50 mg/kg, twice daily for 21 days) did not change significantly [1]
- Macroscopic examination of the liver, kidneys and spleen of mice treated with PF-CBP1 revealed no abnormalities (e.g., hypertrophy, discoloration, necrosis) [1] - The plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and creatinine (Cr) levels of mice treated with PF-CBP1 were all within the normal range and showed no significant difference compared with the vector control group [1] |
| References |
[1]. Chekler EL, et al. Transcriptional Profiling of a Selective CREB Binding Protein Bromodomain Inhibitor Highlights Therapeutic Opportunities. Chem Biol. 2015 Dec 17;22(12):1588-96.
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| Additional Infomation |
PF-CBP1 is a small molecule inhibitor that binds to the acetyllysine binding pocket of the CBP bromodomain, thereby preventing the interaction of CBP with acetylated histones [1] The chemical structure of PF-CBP1 is based on a quinazolinone core optimized for high affinity and selectivity for the CBP bromodomain [1] PF-CBP1 can modulate CBP-dependent transcriptional programs, including those driven by CREB, MYC, and BCL6, which are essential for the survival and proliferation of diffuse large B-cell lymphoma (DLBCL) cells [1] In vitro and in vivo data support PF-CBP1 as a potential treatment for DLBCL and other cancers driven by CBP-dependent transcriptional dysregulation [1]
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| Molecular Formula |
C29H36N4O3
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|---|---|
| Molecular Weight |
488.632
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| Exact Mass |
488.278
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| CAS # |
1962928-21-7
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| Related CAS # |
PF-CBP1 hydrochloride;2070014-93-4
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| PubChem CID |
119081417
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
673.5±55.0 °C at 760 mmHg
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| Flash Point |
361.1±31.5 °C
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| Vapour Pressure |
0.0±2.1 mmHg at 25°C
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| Index of Refraction |
1.615
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| LogP |
5.46
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
36
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| Complexity |
654
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1CCN(CC1)CCN1C2C=CC(C3C(C)=NOC=3C)=CC=2N=C1CCC1C=CC(=CC=1)OCCC
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| InChi Key |
CGWBJJZOKGZCSJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H36N4O3/c1-4-17-35-25-9-5-23(6-10-25)7-12-28-30-26-20-24(29-21(2)31-36-22(29)3)8-11-27(26)33(28)14-13-32-15-18-34-19-16-32/h5-6,8-11,20H,4,7,12-19H2,1-3H3
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| Chemical Name |
4-(2-(5-(3,5-Dimethylisoxazol-4-yl)-2-(4-propoxyphenethyl)-1H-benzo[d]imidazol-1-yl)ethyl)morpholine
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| Synonyms |
PF-CBP-1; PF-CBP1; PF-CBP 1; PF 06670910; PF-06670910; PF06670910
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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
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|---|---|
| Solubility (In Vivo) |
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.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] Oral Formulations
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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0465 mL | 10.2327 mL | 20.4654 mL | |
| 5 mM | 0.4093 mL | 2.0465 mL | 4.0931 mL | |
| 10 mM | 0.2047 mL | 1.0233 mL | 2.0465 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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