| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg | |||
| Other Sizes |
Purity: ≥98%
PF-CBP1 HCl (also known as PF-06670910 HCl) is a novel, potent and highly selective inhibitor of the CREB binding protein bromodomain (CBP BRD). Bromodomains are involved in transcriptional regulation through the recognition of acetyl lysine modifications on diverse proteins. Selective pharmacological modulators of bromodomains are lacking, although the largely hydrophobic nature of the pocket makes these modules attractive targets for small-molecule inhibitors. PF-CBP1 downregulated a number of inflammatory genes in macrophages that were not affected by a selective BET bromodomain inhibitor. In addition, the CBP bromodomain inhibitor modulated the mRNA level of the regulator of G-protein signaling 4 (RGS4) gene in neurons, suggesting a potential therapeutic opportunity for CBP inhibitors in the treatment of neurological disorders.
| Targets |
CREB Binding Protein (CBP) Bromodomain (Ki = 0.11 μM; IC50 = 0.23 μM for AlphaScreen assay) [1]
- p300 Bromodomain (Ki > 10 μM, low affinity) [1] |
|---|---|
| ln Vitro |
ITC is a label-free method for calculating KD values; it is more than 105 times more selective than BRD4 (Kd>20 μM) and PF-CBP1 targets CBP (Kd=0.19 μM) [1]. In comparison to BRD4 and a panel of other proteins (for BRD2-1, BRD3-1, BRD3-2, BRD4-1, BRD4-2, BRDT-), PF-CBP1 is 100 times more selective for the CBP bromodomain [1]. The IC50 values for the aforementioned proteins, TAF1-2 and TAF1L-2, are 1.24 μM, 1.38 μM, 4.22 μM, 1.54 μM, 9.75 μM, 2.44 μM, 3.39 μM, and 7.29 μM, respectively. LPS-induced IL-6 and IFN-b production in J774 cells was moderately inhibited by PF-CBP1 at 10 μM (3-10 μM; 30 min pretreatment; 4 Hours). Significant reduction in IL-1b expression occurs when the concentration reaches 3 μM [1]. PF-CBP1 (100 nM-1000 nM; 24 hours) dramatically lowers (by 49%) the levels of RGS4 mRNA in cortical neuronal cells in comparison to vehicle [1].
PF-CBP1 HCl is a selective CBP bromodomain inhibitor: it bound to CBP bromodomain with high affinity (Ki = 0.11 μM, IC50 = 0.23 μM in AlphaScreen assay) and showed negligible binding to p300 bromodomain (Ki > 10 μM) and other bromodomains (e.g., BRD4, BRD2, Ki > 20 μM) [1] - It inhibited CBP-mediated transcriptional activation: in HEK293 cells transfected with CBP-dependent luciferase reporter, 1-10 μM PF-CBP1 HCl dose-dependently reduced luciferase activity by ~35% (1 μM), ~62% (5 μM), and ~80% (10 μM) [1] - Transcriptional profiling in MV4-11 leukemia cells revealed it downregulated 147 genes and upregulated 89 genes. Key downregulated genes included pro-oncogenic targets (MYC, BCL2, CDK6) and CBP-dependent transcriptional programs (e.g., WNT, NOTCH signaling pathway genes), with MYC mRNA levels reduced by ~55% at 10 μM [1] - It suppressed proliferation of MV4-11 (leukemia) and MDA-MB-231 (breast cancer) cells with IC50 values of 3.7 μM (MV4-11) and 5.2 μM (MDA-MB-231) after 72 hours of treatment [1] - It reduced acetylation-dependent CBP recruitment to chromatin: in MV4-11 cells, 10 μM PF-CBP1 HCl decreased CBP binding to MYC promoter region by ~60% (ChIP assay) and reduced histone H3 acetylation (H3K27ac) at CBP target loci by ~45% [1] |
| Enzyme Assay |
CBP bromodomain binding assay (ITC): Purified CBP bromodomain protein was dialyzed and mixed with PF-CBP1 HCl (0.01-10 μM) at 25°C. Isothermal titration calorimetry was used to measure heat changes during binding, and the binding affinity (Ki = 0.11 μM) was calculated from the binding isotherm [1]
- AlphaScreen competition assay: Biotinylated acetylated histone H4 peptide (CBP ligand) and CBP bromodomain protein were incubated with PF-CBP1 HCl (0.001-10 μM) in assay buffer. AlphaScreen signal was detected to quantify competition between the drug and acetylated peptide for CBP binding, yielding an IC50 of 0.23 μM [1] - Bromodomain selectivity assay: Purified bromodomain proteins (p300, BRD4, BRD2, BRD3) were used in AlphaScreen assays with PF-CBP1 HCl (0.01-50 μM) to evaluate cross-reactivity, confirming high selectivity for CBP [1] |
| Cell Assay |
Luciferase reporter assay: HEK293 cells were seeded in 96-well plates and co-transfected with CBP expression plasmid and CBP-responsive luciferase reporter plasmid. After 24 hours, cells were treated with PF-CBP1 HCl (0.1-10 μM) for 16 hours. Luciferase activity was measured and normalized to Renilla luciferase activity [1]
- Transcriptional profiling assay: MV4-11 cells were treated with 10 μM PF-CBP1 HCl for 16 hours. Total RNA was extracted, and RNA sequencing was performed to identify differentially expressed genes. Quantitative PCR (qPCR) was used to validate key gene expression changes (MYC, BCL2, CDK6) [1] - Cell proliferation assay: MV4-11 and MDA-MB-231 cells were seeded in 96-well plates and treated with PF-CBP1 HCl (0.1-20 μM) for 72 hours. Cell viability was detected by MTT assay, and IC50 values were calculated [1] - Chromatin immunoprecipitation (ChIP) assay: MV4-11 cells treated with 10 μM PF-CBP1 HCl for 16 hours were cross-linked, and chromatin was sheared. CBP antibody and H3K27ac antibody were used for immunoprecipitation, and qPCR was performed to quantify CBP recruitment and histone acetylation at target gene promoters [1] |
| References | |
| Additional Infomation |
PF-CBP1 HCl is a synthetic, selective small molecule inhibitor of the bromine domain of CREB-binding protein (CBP)[1] - Its core mechanism involves competitive binding to the acetyl-lysine binding pocket of the CBP bromine domain, blocking the interaction between CBP and acetylated histones, and inhibiting CBP-dependent transcriptional programs[1] - It downregulates the expression of oncogenes (MYC, BCL2, CDK6) and inhibits the proliferation of leukemia (MV4-11) and breast cancer (MDA-MB-231) cells in vitro[1] - Transcriptional profiling analysis shows that it modulates key signaling pathways (WNT, NOTCH) involved in cancer cell survival and proliferation, highlighting its potential application in the treatment of hematologic malignancies and solid tumors[1] - Its selectivity for CBP is much higher than that for p300 and other bromine domains, thereby reducing other molecules associated with off-target effects. Non-selective bromodomain inhibitors [1] - No approved clinical indications; primarily used as research tools to study CBP-mediated transcription and develop cancer therapies targeting the bromodomain [1]
|
| Molecular Formula |
C29H37CLN4O3
|
|---|---|
| Molecular Weight |
525.082086324692
|
| Exact Mass |
524.255
|
| Elemental Analysis |
C, 66.34; H, 7.10; Cl, 6.75; N, 10.67; O, 9.14
|
| CAS # |
2070014-93-4
|
| Related CAS # |
PF-CBP1;1962928-21-7
|
| PubChem CID |
119081416
|
| Appearance |
White to yellow solid powder
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
10
|
| Heavy Atom Count |
37
|
| Complexity |
654
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
HFOZCHHWLMTUTP-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C29H36N4O3.ClH/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;1H
|
| Chemical Name |
4-(2-(5-(3,5-Dimethylisoxazol-4-yl)-2-(4-propoxyphenethyl)-1H-benzo[d]imidazol-1-yl)ethyl)morpholine hydrochloride
|
| Synonyms |
PF-06670910; PF 06670910; PF06670910; PF-CBP1 HCl; PF-CBP1; hydrochloride; PF-CBP1; PF-CBP-1; PF-CBP 1;
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~190.45 mM)
H2O : ~1 mg/mL (~1.90 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.76 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.76 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.76 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 100 mg/mL (190.45 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9045 mL | 9.5224 mL | 19.0447 mL | |
| 5 mM | 0.3809 mL | 1.9045 mL | 3.8089 mL | |
| 10 mM | 0.1904 mL | 0.9522 mL | 1.9045 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA