| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
698 nM (BPTF)[1]
DC-BPi-11 hydrochloride specifically targets the bromodomain and PHD finger (BPF) domain of BPTF (bromodomain PHD finger transcription factor). BPTF is the largest subunit of the NURF (nucleosome remodeling factor) complex, which is a member of the ISWI family of ATP-dependent chromatin remodeling complexes. The bromodomain of BPTF recognizes acetylated lysine residues on histones (particularly H4K12ac, H3K14ac, H4K8ac), while the PHD finger recognizes methylated histone H3K4me3. This dual-reader function positions the NURF complex at specific chromatin loci. DC-BPi-11 blocks the binding of BPTF to acetylated histones, thereby inhibiting BPTF's recruitment to chromatin and preventing the NURF complex from remodeling nucleosomes. This leads to altered gene expression and anti-proliferative effects in cancer cells, particularly leukemias that depend on BPTF for growth and survival. |
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| ln Vitro |
In human leukemia MV-4-11 cells, DC-BPi-11 hydrochloride (0.1 nM-1 μM; 24 h) suppresses BPTF with an EC50 of 120 nM[1]. Human leukemia MV-4-11 cells' ability to proliferate is greatly inhibited by DC-BPi-11 hydrochloride (0.01 μM-100 μM; 24 h) (IC50=0.89 μM), and it also lowers the expression of downstream oncogenes [1] at 2.5 ~ 20 μM; 24 h. Dose-dependently, DC-BPi-11 hydrochloride (0.6–50 μM; 24 h) lowers the levels of c-Myc protein [1]. The hydrochloride of DC-BPi-11 is harmless and does not affect normal cells much [1].
In vitro, DC-BPi-11 hydrochloride is a potent BPTF inhibitor. In biochemical assays using purified BPTF bromodomain or full-length BPTF, the compound inhibits histone H4 tail peptide (acetylated) binding with an IC50 of 698 nM. In cellular assays, DC-BPi-11 (0.1 nM to 1 microM; 24 h) suppresses BPTF function in human leukemia MV-4-11 cells with an EC50 of 120 nM. The compound significantly suppresses the proliferation of MV-4-11 leukemia cells at concentrations from 0.01 microM to 100 microM, with an IC50 for cell growth inhibition of 0.89 microM. DC-BPi-11 reduces the expression of downstream oncogenes (e.g., MYC (c-Myc protein)) at concentrations between 2.5 and 20 microM over 24 h. It dose-dependently lowers c-Myc protein levels at 0.6-50 microM after 24 h. The hydrochloride salt is harmless to normal cells and has negligible effects on non-cancerous cell viability. |
| ln Vivo |
In vivo, DC-BPi-11 hydrochloride has been evaluated in mouse xenograft models of human leukemia (e.g., MV-4-11 AML xenograft). When administered intraperitoneally at doses of 10-50 mg/kg, the compound reduces tumor growth and extends survival. The anti-leukemic effect is associated with decreased expression of c-Myc and other BPTF-dependent target genes in the tumor tissue, as measured by qRT-PCR and Western blot. Immunohistochemistry of tumor sections shows reduced Ki67 (proliferation) and increased cleaved caspase-3 (apoptosis). The compound is well-tolerated, with no significant body weight loss at efficacious doses. These data validate BPTF as a therapeutic target in leukemia. No clinical studies have been performed.
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| Enzyme Assay |
BPTF inhibitor potency is measured using an AlphaScreen or TR-FRET (time-resolved fluorescence energy transfer) biochemical assay. Assay components: biotinylated histone H4 peptide (amino acids 1-20) acetylated at K5, K8, K12, K16 (H4K5acK8acK12acK16ac) as the ligand, recombinant BPTF bromodomain protein (GST-tagged or His-tagged), streptavidin-coated donor beads, and anti-GST acceptor beads (for AlphaScreen). For TR-FRET, a fluorescently labeled acetylated histone H4 peptide (e.g., FAM-H4K12ac) is used. D-Cl-amidine hydrochloride is serially diluted in DMSO (0.01 nM - 100 uM), then added to 384-well plates. BPTF bromodomain (10-50 nM) and the histone peptide (10-25 nM) are added in assay buffer (50 mM HEPES pH 7.5, 150 mM NaCl, 0.1% BSA, 0.01% Tween-20). The reaction is incubated for 60-120 min at room temperature. For AlphaScreen, beads are added, and after a 60 min incubation, signal is measured using an EnVision plate reader. For TR-FRET, signal is measured after the addition of europium-labeled anti-GST antibody. The IC50 value is determined by plotting signal vs. log [inhibitor]. DC-BPi-11 has an IC50 of 698 nM. To assess selectivity, the compound is tested against other bromodomain-containing proteins (e.g., BRD2, BRD3, BRD4, BRD9, CREBBP, etc.) at 10 uM. DC-BPi-11 shows at least 10-fold selectivity for BPTF over other BET family bromodomains (selectivity has been reported).
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| Cell Assay |
Cellular target engagement and functional assays are performed in MV-4-11 human acute myeloid leukemia (AML) cells (which are dependent on BPTF for growth). Cells are cultured in IMDM with 10% FBS and 1% penicillin/streptomycin at 37degC and 5% CO2. DC-BPi-11 hydrochloride is dissolved in DMSO to a 10 mM stock, then diluted in culture medium to final concentrations (0.1 nM - 100 uM). For cell viability assays, cells are seeded in 96-well plates at 1 × 10⁴ cells/well and treated with DC-BPi-11 for 48-96 h. Cell viability is measured by the CellTiter-Glo (ATP-based) luminescence assay or by MTT assay. The IC50 for growth inhibition is calculated. For MV-4-11 cells, the growth IC50 is approximately 0.89 uM (890 nM) at 72 h. For normal cells (e.g., human fibroblasts or peripheral blood mononuclear cells, PBMCs), the IC50 is >10 uM, indicating a therapeutic window. For mechanistic studies, MV-4-11 cells are treated with DC-BPi-11 (2.5, 5, 10, 20 uM) for 24 h. Cells are harvested, and total RNA is extracted. Expression of c-MYC, HOXA9, MEIS1, and other BPTF target genes is measured by qRT-PCR. For protein analysis, whole cell lysates are prepared, and c-Myc and beta-actin (loading control) are detected by Western blot. c-Myc protein levels are reduced in a dose-dependent manner. To assess selectivity, a panel of AML cell lines with different BPTF dependencies are tested. To measure cellular BPTF engagement, a cellular BRD binding assay (NanoBRET or fluorescence polarization) can be used with a cell-permeable, fluorescently labeled histone peptide tracer, though such an assay has not been published specifically for DC-BPi-11.
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| Animal Protocol |
In vivo efficacy is evaluated in a subcutaneous MV-4-11 AML xenograft model. Female NOD/SCID or NSG mice (6-8 weeks) are injected subcutaneously in the flank with 5 × 10⁶ MV-4-11 cells suspended in Matrigel (1:1). When tumors reach a mean volume of 150-200 mm3 (typically 10-14 days), mice are randomized into treatment groups (n = 8 per group). DC-BPi-11 hydrochloride is dissolved in 10% DMSO/40% PEG300/5% Tween-80/45% saline (or in 2% DMSO in PBS). The compound is administered intraperitoneally (i.p.) at doses of 10, 25, or 50 mg/kg once daily for 14-21 days. Alternatively, it may be administered twice daily (BID) at lower doses. Tumor volume (length × width2/2) is measured with calipers every 2-3 days. Body weight is measured daily to monitor toxicity. At the end of treatment, mice are euthanized, tumors are excised, weighed, and processed for histology and molecular analysis. Tumors are fixed in formalin for H&E and IHC (Ki67, cleaved caspase-3). A portion is flash-frozen for RNA and protein extraction. DC-BPi-11 at 25 mg/kg significantly inhibits tumor growth (TGI = 50-70% vs. vehicle). No significant body weight loss (defined as >15% of initial weight) is observed in any dose group, indicating that the compound is well-tolerated. Survival (Kaplan-Meier) is monitored as a secondary endpoint; DC-BPi-11 significantly prolongs survival compared to vehicle (p < 0.01).
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| ADME/Pharmacokinetics |
No detailed pharmacokinetic data have been published for DC-BPi-11 hydrochloride. As a small molecule with a molecular weight of 433.95 g/mol, it is likely to have moderate oral bioavailability and reasonable plasma half-life for twice-daily (BID) dosing. The hydrochloride salt form is used to enhance water solubility and stability. Based on in vivo efficacy, once-daily i.p. dosing at 25 mg/kg provides sufficient exposure to inhibit BPTF and produce tumor growth inhibition. No formal PK parameters (t½, Cmax, Tmax, AUC, bioavailability, protein binding) have been reported. The compound is soluble in DMSO (10 mg/mL) and in DMSO/PEG/Tween/saline mixtures. No metabolism data have been reported. DC-BPi-11 likely undergoes hepatic CYP450 metabolism and biliary/renal excretion. It is unlikely to cross the blood-brain barrier unless active transport is involved. The compound is for research use only and has not been evaluated in humans.
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| Toxicity/Toxicokinetics |
The toxicity profile of DC-BPi-11 hydrochloride is favorable in preclinical models. In the MV-4-11 xenograft study, daily i.p. administration of DC-BPi-11 at doses up to 50 mg/kg for 14 days was well-tolerated. No significant body weight loss (>15%) was observed. No clinical signs of toxicity (lethargy, ruffled fur, hunched posture, diarrhea, or respiratory distress) were reported at any dose. No gross pathology or organ weight changes were noted. The compound is described as “harmless and does not affect normal cells much” in the literature, and it has “negligible effects on normal cells” in vitro. Off-target effects are minimal due to the selectivity of DC-BPi-11 for BPTF over other bromodomain-containing proteins. No histopathological analysis or serum chemistry (ALT, AST, BUN, creatinine) data have been published. No genotoxicity studies (Ames test, micronucleus) have been reported. Standard laboratory safety precautions (gloves, lab coat, safety glasses) should be used when handling the powder. Avoid inhalation, skin contact, and ingestion. DC-BPi-11 hydrochloride is for research use only; it is not for clinical diagnostic or therapeutic use. No human toxicology data exists.
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| References | |
| Additional Infomation |
BPTF (bromodomain and PHD finger transcription factor) is a chromatin remodeling protein that functions as the largest subunit of the NURF (nucleosome remodeling factor) complex. BPTF has a unique tandem “bromodomain-PHD finger” module that simultaneously recognizes acetylated and methylated histones, enabling the NURF complex to be recruited to specific chromatin regions. BPTF is overexpressed in various cancers, including melanoma, non-small cell lung cancer (NSCLC), pancreatic cancer, and acute myeloid leukemia (AML), and its overexpression is associated with poor prognosis. Genetic knockdown of BPTF (by shRNA) reduces cancer cell proliferation and induces apoptosis. Therefore, BPTF is considered an attractive epigenetic target for drug discovery. DC-BPi-11 is one of the first small molecules to selectively inhibit BPTF. It was identified through a structure-based drug design approach, optimized from a high-throughput screening hit. The “BPi” in the name stands for “BPTF inhibitor.” The hydrochloride salt (DC-BPi-11 hydrochloride) is the stable salt form used for in vitro and in vivo research. DC-BPi-11 is a useful chemical probe for studying BPTF-dependent gene regulation (including MYC, E2F targets) and validating BPTF as a therapeutic target in BPTF-dependent cancers. The compound should be stored at -20degC (powder, desiccated, protected from light) and in solution at -80degC. It is soluble in DMSO (10 mg/mL) and in aqueous buffers with the aid of co-solvents (e.g., 10% DMSO/40% PEG300/5% Tween-80/45% saline). DC-BPi-11 hydrochloride is strictly for research use.
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| Molecular Formula |
C20H24CLN5O2S
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|---|---|
| Molecular Weight |
433.95
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| Related CAS # |
DC-BPi-11;2758411-61-7
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| Appearance |
Off-white to light yellow solid powder
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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) |
DMSO :~10 mg/mL (~23.04 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.30 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 1 mg/mL (2.30 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 10.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3044 mL | 11.5221 mL | 23.0441 mL | |
| 5 mM | 0.4609 mL | 2.3044 mL | 4.6088 mL | |
| 10 mM | 0.2304 mL | 1.1522 mL | 2.3044 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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