| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg | |||
| Other Sizes |
| Targets |
Bromodomain-containing protein 9 (BRD9) and Bromodomain-containing protein 7 (BRD7). TP-472 is a potent and selective inhibitor of the bromodomains of BRD9 and BRD7. It has a Kd (binding affinity) of 33 nM for BRD9 and a Kd of 340 nM for BRD7, exhibiting >30-fold selectivity for BRD9 over all other bromodomain family members except the highly homologous BRD7. This selectivity allows it to specifically disrupt the interaction between BRD9/7 and acetylated histones, thereby modulating transcription of downstream target genes.
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| ln Vitro |
Concentration-dependent growth abnormalities in ESCs are caused by TP-472 (1 µM, 3 µM; 24-216 hours) [2]. At dosages of 5 and 10 μM, TP-472 (0.1-10 μM; 24 hours) efficiently suppresses the development of BRAF mutant melanoma cell lines [3]. At doses of 5 and 10 µM, TP-472 also significantly reduces the long-term survival of several melanoma cell lines (M14, SKMEL-28, A375, and A2058; this effect lasts for two weeks) [3]. When A375 cells are treated with TP-472 (5–10 μM) for 24 hours, the genes that encode several extracellular matrix (ECM) proteins, such as integrins, collagen, and fibronectin, are downregulated [3]. In A375 cells, TP-472 (0.1-10 μM; 24 hours) induces pro-apoptotic genes (BAX, MDM2, CDKN1A) to be upregulated [3].
In cell-free assays, TP-472 binds to BRD9 with a Kd of 33 nM, as measured by isothermal titration calorimetry (ITC). In cellular NanoBRET assays, it exhibits an EC₅0 of 320 nM. In cell culture models, TP-472 inhibits the proliferation of melanoma cells and other BRD9-dependent cancer cells by inducing apoptosis and disrupting extracellular matrix (ECM)-mediated oncogenic signaling. It upregulates several pro-apoptotic genes and decreases cell viability in a dose-dependent manner. |
| ln Vivo |
TP-472 (20 mg/kg; i.p.; 3 times per week; for 5 weeks) effectively suppressed subcutaneous tumor growth in a melanoma xenograft mice model [3].
In vivo, TP-472 demonstrates significant anti-tumor efficacy in preclinical mouse models of melanoma. Administered via intraperitoneal (i.p.) injection at a dose of 20 mg/kg three times per week for up to 5 weeks, TP-472 effectively blocks melanoma tumor growth in xenograft-based mouse models. The treatment leads to tumor growth inhibition, increased apoptosis within the tumor, and improved long-term survival in treated mice. This demonstrates its potential utility as a therapeutic agent for melanoma. |
| Enzyme Assay |
A TR-FRET (Time-Resolved Fluorescence Resonance Energy Transfer) assay is used. Recombinant BRD9 bromodomain protein is incubated with a biotinylated acetylated histone peptide and increasing concentrations of TP-472 (0.001-10 uM). Streptavidin-Allophycocyanin (APC) and anti-GST-Europium antibodies are added. Upon excitation at 340 nm, energy transfer from Europium to APC occurs if the peptide is bound to BRD9. TP-472 competitively disrupts this interaction, causing a decrease in the 665/620 nm emission ratio. IC₅0 is calculated.
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| Cell Assay |
Cell Viability Assay[2]
Cell Types: Embryonic Stem Cells Tested Concentrations: 1 µM, 3 µM Incubation Duration: 24 hrs (hours), 72 hrs (hours), 120 hrs (hours), 168 hrs (hours), 216 hrs (hours) Experimental Results: Concentration-dependent growth defects in ESCs. Cell proliferation assay[3] Cell Types: M14 and SKMEL-28 cells[3] Tested Concentrations: 0.1 μM, 0.5 μM, 1 μM, 2 μM, 5 μM, 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Effectively inhibited the growth of both BRAF mutant melanoma cell lines. Western Blot Analysis[3] Cell Types: A375 Cell Tested Concentrations: 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Result in upregulation of pro-apoptotic genes. A375 melanoma cells or other suspension cells are seeded in 96-well plates and treated with a dose-response of TP-472 (e.g., 0.1-10 uM) for 48-72 hours. Cell viability is measured using the CellTiter-Glo 2.0 reagent, which quantifies ATP levels. For apoptosis detection, cells treated with the compound are stained with Annexin V-FITC and Propidium Iodide (PI) and analyzed by flow cytometry. To assess protein changes, cells are lysed and immunoblotted for cleaved PARP and pro-apoptotic markers. |
| Animal Protocol |
Animal/Disease Models: NSG mice (male, five to six weeks old) injected with A375-MA2 cells [3]
Doses: 20 mg/kg Route of Administration: intraperitoneal (ip) injection; three times a week; for 5 consecutive weeks Experimental Results: Dramatically inhibited melanoma subcutaneoustumor growth in xenograft mouse models. Female NOD-scid IL2Rgamma-/- (NSG) mice are injected subcutaneously with 5 × 10⁶ A375 melanoma cells in 50% Matrigel. When tumors reach an average volume of ~150 mm3, mice are randomized (n=6-10 per group). TP-472 is dosed at 20 mg/kg in a vehicle (e.g., 10% DMSO/90% corn oil) via intraperitoneal (i.p.) injection three times per week for 5 weeks. Tumor volumes are measured twice weekly with calipers. Mice are euthanized when tumors reach 2000 mm3 or at study end. Tumors are excised, weighed, and processed for histology (H&E, TUNEL staining) and protein analysis. |
| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for TP-472 is not published in the search results. As a bromodomain inhibitor with robust in vivo efficacy, it is likely to have suitable properties for systemic administration via intraperitoneal (i.p.) injection. The compound has a molecular weight of 333.38 and a predicted high permeability. It is soluble in DMSO, supporting in vivo formulation. The specific half-life (t1/2), clearance (CL), and oral bioavailability (F%) remain to be characterized by further studies.
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| Toxicity/Toxicokinetics |
Specific toxicology data for TP-472 is not available. In preclinical animal models, the reported effective dose (20 mg/kg i.p., thrice weekly) was well-tolerated, with no reports of significant weight loss or mortality in the mice during the treatment period. However, as with any selective epigenetic probe, on-target toxicity cannot be ruled out. Standard safety precautions for handling research chemicals should be followed, including the use of PPE and working within a fume hood.
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| References |
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| Additional Infomation |
TP-472 is a high-quality research chemical probe widely used for target validation. It is not a clinically approved drug and has not advanced to human clinical trials. It is considered a first-in-class probe for BRD9, particularly useful for studying synovial sarcoma and melanoma. An inactive control analog (TP-472N) is available for target deconvolution. It is supplied at high purity (≥98%) for biological and pharmacological research.
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| Molecular Formula |
C₂₀H₁₉N₃O₂
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|---|---|
| Molecular Weight |
333.38
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| Exact Mass |
333.147
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| CAS # |
2079895-62-6
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| PubChem CID |
123773279
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.681
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| LogP |
1.25
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
533
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C=C(C=C1)C(=O)NC2CC2)C3=C4N=CC=CN4C(=C3)C(=O)C
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| InChi Key |
RPBMXJHQYJLPDN-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H19N3O2/c1-12-4-5-14(20(25)22-15-6-7-15)10-16(12)17-11-18(13(2)24)23-9-3-8-21-19(17)23/h3-5,8-11,15H,6-7H2,1-2H3,(H,22,25)
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| Chemical Name |
3-(6-acetylpyrrolo[1,2-a]pyrimidin-8-yl)-N-cyclopropyl-4-methylbenzamide
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| Synonyms |
TP472 TP 472
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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 : ~100 mg/mL (~299.96 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.50 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 (7.50 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9996 mL | 14.9979 mL | 29.9958 mL | |
| 5 mM | 0.5999 mL | 2.9996 mL | 5.9992 mL | |
| 10 mM | 0.3000 mL | 1.4998 mL | 2.9996 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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