TP-472 is a selective BRD9/7 inhibitor (antagonist) with Kds of 33 nM and 340 nM for BRD9 and BRD7, respectively. TP-472 is more than 30-fold more selective for BRD9 than other bromodomain family members except BRD7. TP-472 causes apoptosis in melanoma cells.

Physicochemical Properties

Molecular Formula	C₂₀H₁₉N₃O₂
Molecular Weight	333.38
Exact Mass	333.147
CAS #	2079895-62-6
PubChem CID	123773279
Appearance	Light yellow to yellow solid powder
Density	1.3±0.1 g/cm3
Index of Refraction	1.681
LogP	1.25
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	4
Heavy Atom Count	25
Complexity	533
Defined Atom Stereocenter Count	0
InChi Key	RPBMXJHQYJLPDN-UHFFFAOYSA-N
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)
Chemical Name	3-(6-acetylpyrrolo[1,2-a]pyrimidin-8-yl)-N-cyclopropyl-4-methylbenzamide
Synonyms	TP472 TP 472
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
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

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].
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].
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.
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.
References	[1]. Chemical probes and inhibitors of bromodomains outside the BET family. Medchemcomm. 2016 Dec 7;7(12):2246-2264. [2]. A non-canonical BRD9-containing BAF chromatin remodeling complex regulates naive pluripotency in mouse embryonic stem cells. Nat Commun. 2018 Dec 3;9(1):5139. [3]. The BRD9/7 Inhibitor TP-472 Blocks Melanoma Tumor Growth by Suppressing ECM-Mediated Oncogenic Signaling and Inducing Apoptosis. Cancers (Basel). 2021 Nov 3;13(21):5516.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~299.96 mM)

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.