ERX-41 is an orally bioavailable, stereospecific small molecule targeting lysosomal acid lipase A (LIPA). ERX-41 induces endoplasmic reticulum (ER) stress leading to cell death, indicating that its function is independent of LIPA but dependent on its ER localization. ERX-41 is involved in targeted studies in solid tumors.

Physicochemical Properties

Molecular Formula	C38H48N4O9
Molecular Weight	704.80913066864
Exact Mass	704.342
CAS #	2440087-54-5
PubChem CID	153603617
Appearance	Off-white to light yellow solid powder
LogP	6.7
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	9
Rotatable Bond Count	15
Heavy Atom Count	51
Complexity	1130
Defined Atom Stereocenter Count	0
InChi Key	QOYORXKDWMJNHD-UHFFFAOYSA-N
InChi Code	InChI=1S/C38H48N4O9/c1-23(2)21-50-33-18-26(36(44)39-29-11-6-25(5)7-12-29)8-13-30(33)40-37(45)27-9-14-31(34(19-27)51-22-24(3)4)41-38(46)28-10-15-32(42(47)48)35(20-28)49-17-16-43/h8-10,13-15,18-20,23-25,29,43H,6-7,11-12,16-17,21-22H2,1-5H3,(H,39,44)(H,40,45)(H,41,46)
Chemical Name	4-[[4-[[3-(2-hydroxyethoxy)-4-nitrobenzoyl]amino]-3-(2-methylpropoxy)benzoyl]amino]-N-(4-methylcyclohexyl)-3-(2-methylpropoxy)benzamide
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: (1). This product requires protection from light (avoid light exposure) during transportation and storage.(2). Please store this product in a sealed and protected environment (e.g. under nitrogen), 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	Lysosomal acid lipase A (LIPA)[1]
ln Vitro	ERX-41 (1 μM; 0-30 h) causes MDA-MB-231 cells to die, while normal human mammary epithelial cells (HMECs) are not significantly affected [1]. Peripheral endoplasmic reticulum disorder is caused within 2 hours of exposure to ERX-41 (1 μM; 2 h, 4 h) and causes a dramatic expansion of the endoplasmic reticulum within 4 hours [1]. The downstream unfolded protein response (UPR) pathway is induced by ERX-41 (1 μM; 0.5–4 h) through the induction of p-PERK and p-eIF2-α [1].
ln Vivo	ERX-41 (10 mg/kg; oral or intraperitoneal injection; single dose) is seen in tumors 1.5 hours after intraperitoneal or oral administration[1]. In the MDA-MB-231 xenograft mouse model, ERX-41 (10 mg/kg; oral; single dose) effectively reduces tumor development without altering animal body weight[1]. In D2A1 xenograft animal models, ERX-41 (10 mg/kg; oral; single dosage) dramatically slows the course of the disease[1].
Cell Assay	Cell Viability Assay[1] Cell Types: MDA-MB-231 and HMEC cells Tested Concentrations: 1 μM Incubation Duration: 0, 20 h, 30 h Experimental Results: demonstrated potent antiproliferative activity against TNBC cell within 30 h. Western Blot Analysis[1] Cell Types: SUM-159 cells Tested Concentrations: 1 μM Incubation Duration: 0.5 h, 1 h, 2 h, and 4 h Experimental Results: Increased the protein level of p-PERK, p-eIF2-α and CHOP at 4 h. Cell Cytotoxicity Assay[1] Cell Types: SUM-159 and MDA-MB-436 Tested Concentrations: 0.125, 0.25, 0.50, 1.0, 2.0, and 4.0 μM Incubation Duration: 0h and 30 h Experimental Results: Caused cell death.
Animal Protocol	Animal/Disease Models: Mouse models with D2A1 xenografts and MDA-MB-231 xenografts (sc), respectively[1] Doses: 10 mg/kg Route of Administration: Oral gavage; one time/day for 25 days Experimental Results: decreased tumor growth against MDA-MB-231 xenograft without affecting body weight. And enhanced p-PERK and p-eIF2-α staining within 24 h. Dramatically decreased the growth of D2A1 xenografts in syngeneic mice without affecting body weight.
References	[1]. Targeting LIPA independent of its lipase activity is a therapeutic strategy in solid tumors via induction of endoplasmic reticulum stress. Nat Cancer. 2022 Jul;3(7):866-884.

Solubility Data

Solubility (In Vitro)

DMSO: 25 mg/mL (35.47 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (3.55 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	1.4188 mL	7.0941 mL	14.1882 mL
	5 mM	0.2838 mL	1.4188 mL	2.8376 mL
	10 mM	0.1419 mL	0.7094 mL	1.4188 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.