PRGL493 is a potent and specific inhibitor of long-chain acyl-CoA synthetase 4 (ACSL4). PRGL493 blocks cell proliferation/growth and tumor growth in both breast and prostate cells and animal models. PRGL493 may be used in cancer research.

Physicochemical Properties

Molecular Formula	C25H21N7O2
Molecular Weight	451.479943990707
Exact Mass	451.175
CAS #	2479378-45-3
PubChem CID	154685871
Appearance	White to off-white solid powder
LogP	3.3
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	4
Heavy Atom Count	34
Complexity	787
Defined Atom Stereocenter Count	0
SMILES	O1C(C)=CC=C1C1C(=CN(C2C=CC=CC=2)N=1)C1N=C(NC(C)=O)NC2=NC3C=CC=CC=3N12
InChi Key	QNWGOBIYAPLFMK-UHFFFAOYSA-N
InChi Code	InChI=1S/C25H21N7O2/c1-15-12-13-21(34-15)22-18(14-31(30-22)17-8-4-3-5-9-17)23-28-24(26-16(2)33)29-25-27-19-10-6-7-11-20(19)32(23)25/h3-14,23H,1-2H3,(H2,26,27,28,29,33)
Chemical Name	N-[4-[3-(5-methylfuran-2-yl)-1-phenylpyrazol-4-yl]-1,4-dihydro-[1,3,5]triazino[1,2-a]benzimidazol-2-yl]acetamide
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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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

Targets	IC50: ACSL4[1]
ln Vitro	An isoenzyme of the fatty acid ligase-CoA family involved in steroidogenesis and arachidonic acid metabolism is called acyl-CoA synthetase 4 (ACSL4) [1]. Reductions in AA-CoA levels show that PRGL493 ([ 3H]-AA (0.5 μCi/mL in serum-free media) 3 hours; 48 hours) strongly inhibits ACSL4 in all three cell lines (MDA-MB-231, PC-3, and MA-10) of active Leydig cells. PRGL493, however, had no impact on the expression of the ACSL4 protein [1]. With IC50s of 23 μM and 27 μM, respectively, PRGL493 (20-100 μM; 72 hours) suppresses the proliferation of highly aggressive breast and prostate cancer cells [1].
ln Vivo	Tumor development and volume were decreased by PRGL493 (intraperitoneal injection; 250 μg/Kg; consecutive days 43 and 34). Additionally, in breast and prostate xenograft tumors, the drug boosted ER and AR expression and decreased Ki67 protein expression[1].
Animal Protocol	Animal/Disease Models: MDA-MB-231 or PC-3 cell suspensions mixed with Matrigel Matrix in a 3/1 dilution are injected into the right fank of NLAE:NIH(S)Fox1nu (nude) mice , aged 7-8 weeks[1] Doses: 250 μg/kg Route of Administration: intraperitoneal (ip) injection; 250 μg/kg; 43 and 34 days Experimental Results: Inhibited tumor growth in vivo models
References	[1]. New inhibitor targeting Acyl-CoA synthetase 4 reduces breast and prostate tumor growth, therapeutic resistance and steroidogenesis. Cell Mol Life Sci. 2021 Mar;78(6):2893-2910.

Solubility Data

Solubility (In Vitro)

DMSO: 5 mg/mL (11.07 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.25 mg/mL (2.77 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 12.5 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: ≥ 1.25 mg/mL (2.77 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 12.5 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: ≥ 1.25 mg/mL (2.77 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 12.5 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	2.2149 mL	11.0747 mL	22.1494 mL
	5 mM	0.4430 mL	2.2149 mL	4.4299 mL
	10 mM	0.2215 mL	1.1075 mL	2.2149 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.