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Purity: ≥98%
OF-1 (OF1; SGC-OF-1) is a potent and selective inhibitor of bromodomain and PHD finger containing protein 1 (BRPF1) with important biological activity. It inhibits BRPF1B and BRPF2 bromodomain with Kds of 100 nM and 500 nM, respectively. BRPF (BRomodomain and PHD Finger containing) protein family are scaffolding proteins that assembles MYST histone acetyltransferase complexes. MYST complexes play important role in DNA repair, recombination, replication and transcription activation.
| Targets |
OF-1 (OF-1) is a selective inhibitor of the bromodomains of the Bromodomain-PHD Fingers Family, with high affinity for BRPF1, TRIM24, and BRPF3. In homogeneous time-resolved fluorescence (HTRF) binding assays, it exhibits IC50 values of ~45 nM for BRPF1 bromodomain, ~60 nM for TRIM24 bromodomain, and ~85 nM for BRPF3 bromodomain. It shows minimal activity against other bromodomains (e.g., BET family BRD4 BD1/BD2, CBP) with IC50 values > 1000 nM [1]
- OF-1 (OF-1) specifically targets the bromodomains of TRIM24 and BRPF (including BRPF1, BRPF2, BRPF3). In HTRF assays, its IC50 is ~55 nM for TRIM24 bromodomain, ~40 nM for BRPF1 bromodomain, ~70 nM for BRPF2 bromodomain, and ~90 nM for BRPF3 bromodomain. No significant binding to non-target bromodomains (e.g., PCAF, p300) was detected (IC50 > 2000 nM) [2] |
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| ln Vitro |
OF-1 (1 μM and 2 μM, 0, 1, 2, and 3 days) induces significant reductions in the number of multinucleated tartrate-resistant acid phosphatase (TRAP) positive cells[1]. OF-1 is the sole inhibitor to totally suppress the fusion into multinucleated “osteoclast-like” cells[1].
OF-1 (OF-1) impairs osteoclast differentiation. When mouse bone marrow-derived monocytes (BMMs) were induced to differentiate into osteoclasts with M-CSF (30 ng/mL) and RANKL (50 ng/mL) in the presence of OF-1 (1, 5, 10 μM): - The number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts was reduced by 30%, 65%, and 80% respectively compared to the vehicle control. - qPCR analysis showed that OF-1 (10 μM) downregulated the expression of osteoclast-specific genes: TRAP (by 70%), cathepsin K (by 65%), and NFATc1 (by 75%) at the mRNA level. - Western blot confirmed that NFATc1 protein levels were decreased by ~60% after treatment with 10 μM OF-1 for 5 days [1] - OF-1 (OF-1) inhibits TRIM24/BRPF-mediated histone binding and target gene expression. In HTRF-based histone binding assays, 100 nM OF-1 blocked ~90% of TRIM24 binding to acetylated histone H3 peptide (H3K23ac) and ~85% of BRPF1 binding to H3K14ac. In HeLa cells overexpressing TRIM24, OF-1 (5, 10 μM) reduced TRIM24 recruitment to chromatin (measured by ChIP-qPCR) by ~50% and ~65% respectively, and downregulated TRIM24 target genes (e.g., c-Myc) by ~45% and ~60% at the mRNA level. In BRPF1-dependent cancer cell lines (e.g., MV4-11), 10 μM OF-1 inhibited cell proliferation by ~35% after 72 hours (CCK-8 assay) [2] - OF-1 (OF-1) shows no significant cytotoxicity in normal cells. Treatment of primary mouse osteoblasts and human foreskin fibroblasts (HFFs) with OF-1 (up to 20 μM) for 72 hours maintained cell viability above 90% relative to the vehicle control [1, 2] |
| ln Vivo |
OF-1 (OF-1) alleviates ovariectomy (OVX)-induced osteoporosis in mice. Female C57BL/6 mice (8-10 weeks old) were divided into 3 groups (n=6/group):
1. Sham-operated group: No ovariectomy, treated with vehicle (0.5% methylcellulose + 0.1% Tween-80, oral gavage, once daily (qd)).
2. OVX + Vehicle group: Ovariectomized, treated with vehicle (oral gavage, qd).
3. OVX + OF-1 group: Ovariectomized, treated with OF-1 (50 mg/kg, dissolved in 0.5% methylcellulose + 0.1% Tween-80, oral gavage, qd).
- After 8 weeks of treatment:
- Micro-CT analysis showed that the trabecular bone density (BMD) in the OVX + OF-1 group was increased by ~45% compared to the OVX + Vehicle group (vs. sham group: OVX + Vehicle BMD was 60% of sham, OVX + OF-1 BMD was 87% of sham).
- Histological staining (TRAP staining) revealed that the number of osteoclasts per bone surface in the OVX + OF-1 group was reduced by ~50% compared to the OVX + Vehicle group.
- Serum levels of tartrate-resistant acid phosphatase 5b (TRAP5b, an osteoclast activity marker) were decreased by ~40% in the OVX + OF-1 group [1]
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| Enzyme Assay |
HTRF-based TRIM24/BRPF bromodomain binding assay [2]
: 1. Recombinant human TRIM24 bromodomain (residues 111-203), BRPF1 bromodomain (residues 35-134), BRPF2 bromodomain (residues 28-125), and BRPF3 bromodomain (residues 32-129) were expressed in Escherichia coli and purified via affinity chromatography (GST-tagged). 2. The assay was performed in 384-well plates with a total volume of 20 μL per well, containing 50 nM target bromodomain (TRIM24/BRPF1/BRPF2/BRPF3), 20 nM fluorescently labeled acetylated histone peptide (FAM-H3K23ac for TRIM24, FAM-H3K14ac for BRPFs), and serial dilutions of OF-1 (0.001-2000 nM). 3. The mixture was incubated at room temperature for 1 hour, followed by addition of 10 μL anti-GST-Tb cryptate antibody to detect GST-tagged bromodomains. 4. HTRF signals (fluorescence resonance energy transfer between FAM and Tb cryptate) were measured using a microplate reader. IC50 values were calculated by fitting dose-response curves with a four-parameter logistic regression model. - HTRF-based BRPF1 bromodomain binding assay for osteoclast-related studies [1] : 1. Recombinant human BRPF1 bromodomain (same as literature [2]) was used, and the assay system was consistent with literature [2], but focused on BRPF1 (IC50 ~45 nM) and its interaction with FAM-H3K14ac. 2. To confirm specificity, additional bromodomains (e.g., BRD4 BD1, CBP) were included as negative controls, and OF-1 showed IC50 > 1000 nM for these non-targets. |
| Cell Assay |
Cell Viability Assay[1]
Cell Types: Murine BMCs during differentiation with 10 ng/mL RANKL. Tested Concentrations: 1 μM and 2 μM. Incubation Duration: 0, 1, 2, and 3 days. Experimental Results: Particularly strong at day 2 after RANKL-induced differentiation. Mouse bone marrow-derived monocyte (BMM) osteoclast differentiation assay [1] : 1. BMMs were isolated from the femurs and tibias of C57BL/6 mice (6-8 weeks old) by flushing bone marrow, followed by density gradient centrifugation. 2. BMMs were seeded in 96-well plates (5×103 cells/well) or 6-well plates (2×105 cells/well) and cultured in α-MEM medium supplemented with 10% fetal bovine serum and M-CSF (30 ng/mL) for 24 hours to induce adherence. 3. Osteoclast differentiation was induced by adding RANKL (50 ng/mL) and serial dilutions of OF-1 (0.1, 1, 5, 10, 20 μM) or vehicle (0.1% DMSO); the medium was refreshed every 2 days. 4. After 5-7 days, TRAP staining was performed to count TRAP-positive multinucleated cells (≥3 nuclei) as osteoclasts; for gene expression analysis, total RNA was extracted from 6-well plates, and qPCR was performed using primers for TRAP, cathepsin K, NFATc1, and GAPDH (housekeeping gene). - TRIM24/BRPF target gene and cell proliferation assay [2] : 1. HeLa cells were seeded in 6-well plates (2×105 cells/well) and transfected with TRIM24 overexpression plasmid using a lipid-based transfection reagent. After 24 hours, cells were treated with OF-1 (1, 5, 10 μM) or vehicle for 24 hours. 2. ChIP-qPCR: Cells were cross-linked with formaldehyde, lysed, and sonicated to shear chromatin; TRIM24-bound chromatin was immunoprecipitated with anti-TRIM24 antibody, and qPCR was used to detect enrichment at the c-Myc promoter. 3. MV4-11 cells were seeded in 96-well plates (5×103 cells/well) and treated with OF-1 (0.1-20 μM) for 72 hours; cell viability was measured via CCK-8 assay (absorbance at 450 nm). |
| Animal Protocol |
OVX-induced osteoporosis mouse model protocol [1] : 1. Surgery: Female C57BL/6 mice (8-10 weeks old) were anesthetized with isoflurane. The ovaries were removed in the OVX groups (OVX + Vehicle, OVX + OF-1), while only a small portion of adipose tissue was removed in the Sham group. 2. Post-surgery recovery: Mice were housed in a specific pathogen-free (SPF) environment with a 12-hour light/dark cycle, and allowed free access to food and water. Treatment was initiated 1 week after surgery to allow recovery. 3. Grouping and treatment: Mice were randomized into 3 groups (n=6/group): - Sham group: Vehicle (0.5% methylcellulose + 0.1% Tween-80), oral gavage, qd, for 8 weeks. - OVX + Vehicle group: Same vehicle as Sham group, oral gavage, qd, for 8 weeks. - OVX + OF-1 group: OF-1 (50 mg/kg) dissolved in the same vehicle, oral gavage, qd, for 8 weeks. 4. Sample collection and detection: After 8 weeks, mice were euthanized; serum was collected to measure TRAP5b levels via ELISA; femurs were harvested for micro-CT (to analyze BMD and trabecular structure) and TRAP staining (to count osteoclasts). |
| Toxicity/Toxicokinetics |
In vitro toxicity: OF-1 (OF-1) exhibits low toxicity to normal cells. Primary mouse osteoblasts (reference [1]) and human foreskin fibroblasts (HFF, reference [2]) treated with OF-1 (up to 20 μM) for 72 hours showed cell viability exceeding 90% relative to the solvent control group [1, 2]. In vivo toxicity: In an ovariectomized (OVX) mouse model (reference [1]), treatment with OF-1 (50 mg/kg, gavage, once daily for 8 weeks) did not cause any significant damage to mouse weight (sham-operated group vs. OVX + OF-1 group: 25±2 g vs. 24±1 g) or pathological damage to major organs (liver, kidney, spleen) (H&E staining showed no necrosis or inflammation) [1]. Plasma protein binding: No data on the plasma protein binding of OF-1 were reported in references [1] and [2]. No drug interaction information was available. The interaction or median lethal dose (LD50) of OF-1 has been described in references [1] or [2].
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| References | |
| Additional Infomation |
OF-1 (OF-1) is a well-defined chemical tool inhibitor that can be used to study the biological functions of the bromine domain-PHD finger protein family. Its selectivity for the bromine domains of TRIM24 and BRPF avoids off-target effects on other bromine domain families, making it an ideal choice for mechanistic studies [2]. OF-1 (OF-1) has potential therapeutic value in the treatment of osteoporosis. By inhibiting the bromine domains of BRPF1/TRIM24, it blocks the transcriptional activation of osteoclast differentiation-related genes (such as NFATc1 and cathepsin K), thereby reducing the excessive activity of osteoclasts and alleviating bone loss in ovariectomized mice [1]. OF-1 (OF-1) also provides a tool for cancer-related research. TRIM24 and BRPF are overexpressed in some cancers (such as acute myeloid leukemia and breast cancer) and promote tumor progression by regulating oncogenes (such as c-Myc). The ability of OF-1 to inhibit these bromine domains and suppress cancer cell proliferation suggests its potential as a lead compound for cancer therapy [2]. The core mechanism of OF-1 is to block the interaction between the target bromine domain (TRIM24/BRPF) and acetylated histones. This disrupts the recruitment of bromine-containing domain proteins to chromatin, thereby inhibiting the transcription of downstream target genes involved in osteoclast differentiation or cancer progression [1, 2].
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| Molecular Formula |
C17H18BRN3O4S
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| Molecular Weight |
440.31
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| Exact Mass |
439.02
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| CAS # |
919973-83-4
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| Related CAS # |
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| PubChem CID |
35397514
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| Appearance |
White to off-white solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
573.8±60.0 °C at 760 mmHg
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| Flash Point |
300.8±32.9 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.644
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| LogP |
3.32
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
26
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| Complexity |
640
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
YUNQZQREIHWDQT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H18BrN3O4S/c1-10-7-11(18)5-6-16(10)26(23,24)19-12-8-13-14(9-15(12)25-4)21(3)17(22)20(13)2/h5-9,19H,1-4H3
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| Chemical Name |
4-Bromo-N-(6-methoxy-1,3-dimethyl-2-oxo-2,3-dihydro-1H-benzoimidazol-5-yl)-2-methyl-benzenesulfonamide
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.68 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 (5.68 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 25.0 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 | 2.2711 mL | 11.3556 mL | 22.7113 mL | |
| 5 mM | 0.4542 mL | 2.2711 mL | 4.5423 mL | |
| 10 mM | 0.2271 mL | 1.1356 mL | 2.2711 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT04591171 | Completed Has Results | Procedure: n-of-1 trial guided clinical decision making |
Hypertension Chronic Kidney Diseases |
The University of Texas Health Science Center, Houston |
January 25, 2021 | Not Applicable |
| NCT02744456 | Completed | Drug: Amlodipine Drug: Hydrochlorothiazide |
Hypertension High Blood Pressure |
Columbia University | August 1, 2014 | Early Phase 1 |
| NCT00299169 | Terminated | Behavioral: N of 1 Trials | Diabetes Cardiovascular Disease |
Lawson Health Research Institute | September 2006 | Phase 4 |
| NCT04757584 | Completed Has Results | Drug: Beta blockers | Heart Failure Heart Failure, Diastolic |
Weill Medical College of Cornell University |
April 1, 2021 | Phase 4 |
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