BRM/BRG1 ATP Inhibitor-1 is an orally bioactive inhibitor of Brahma Homolog (BRM)/SMARCA2 ATPase with anticancer activity and has potential to be used for the treatment of Brahma Related Gene 1 (BRG1)/SMARCA4-Mutant Cancers. It inhibits BRM/BRG1 ATP with an IC50 of 5 nM.

Physicochemical Properties

Molecular Formula	C11H9F3N4O2S
Molecular Weight	318.274970769882
Exact Mass	318.04
Elemental Analysis	C, 41.51; H, 2.85; F, 17.91; N, 17.60; O, 10.05; S, 10.07
CAS #	2270879-17-7
PubChem CID	137701967
Appearance	White to off-white solid powder
LogP	1.6
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	4
Heavy Atom Count	21
Complexity	366
Defined Atom Stereocenter Count	0
InChi Key	CKYCAIAVJIFWPE-UHFFFAOYSA-N
InChi Code	InChI=1S/C11H9F3N4O2S/c12-8-1-6(5(4-19)3-15-8)16-11(20)17-9-2-7(10(13)14)18-21-9/h1-3,10,19H,4H2,(H2,15,16,17,20)
Chemical Name	1-[3-(difluoromethyl)-1,2-thiazol-5-yl]-3-[2-fluoro-5-(hydroxymethyl)pyridin-4-yl]urea
Synonyms	BRM/BRG1 ATP Inhibitor-1; CUN79177; CUN79177; CUN-79177; NVP-RXI570; NVP-RXI-570; NVP-RXI 570;
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	BRM/BRG1 ATP Inhibitor-1 (compound 14) has the ability to inhibit locomotor proliferation at concentrations of 0–10 μM over a 5-day period [1]. With an AAC50 (absolute AC50) value of 0.01 μM in H1299 cells and 0.01 μM in RERF-LC-AI cells, BRM/BRG1 ATP Inhibitor-1 suppresses the expression of the KRT80 gene [1].
ln Vivo	Tumor growth and KRT80 expression can be inhibited in a dose-dependent manner by BRM/BRG1 ATP Inhibitor-1 (Compound 14) (lateral wall, 7.5 or 20 mg/kg, daily, 3 weeks) [1].
Cell Assay	Cell proliferation assay [1] Cell Types: SKMEL5 melanoma cells and SBC-5 small cell carcinoma Tested Concentrations: 0-10 μM Incubation Duration: 5 days Experimental Results: Inhibition of proliferation of SKMEL5 cells, AAC50 (absolute AC50) value is 0.004 μM, inhibition Proliferation of SBC-5 cells, AAC50 is greater than 10μM.
Animal Protocol	Animal/Disease Models: Female athymic nude mice with RERF-LC-AI tumor xenografts [1] Doses: 7.5 mg/kg, 20 mg/kg Route of Administration: Oral; daily; 3-week Experimental Results: 7.5 mg/kg and 20 mg/kg doses inhibited tumor growth by 21% and 55%, respectively. The inhibition rate of KRT80 expression was as high as 90% 7 hrs (hrs (hours)) after administration of 20 mg/kg.
References	[1]. Discovery of Orally Active Inhibitors of Brahma Homolog (BRM)/SMARCA2 ATPase Activity for the Treatment of Brahma Related Gene 1 (BRG1)/SMARCA4-Mutant Cancers. J Med Chem. 2018 Nov 21;61(22):10155-10172.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~785.50 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.54 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 20.8 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: ≥ 2.08 mg/mL (6.54 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 20.8 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. Solubility in Formulation 3: ≥ 2.08 mg/mL (6.54 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 20.8 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	3.1419 mL	15.7094 mL	31.4189 mL
	5 mM	0.6284 mL	3.1419 mL	6.2838 mL
	10 mM	0.3142 mL	1.5709 mL	3.1419 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.