: MX69 (MX-69) is a novel, potent and selective MDM2/XIAP dual inhibitor that has the potential use for treatment of cancer. MX69 prevents MDM2 from being degraded by preventing the MDM2 protein from interacting with XIAP RNA. In vitro testing of MX69 on healthy human hematopoiesis revealed little inhibition, and animal models of the drug demonstrated very high levels of tolerability. MX69-induced MDM2 downregulation results not only in inhibition of XIAP expression, but also in activation of p53, which contributes to cancer cell apoptosis in vitro and inhibition of cancer cell proliferation in vivo. The compound-induced MDM2 downregulation resulted not only in inhibition of XIAP expression, but also in activation of p53, which contributed to cancer cell apoptosis in vitro and inhibition of cancer cell proliferation in vivo. Importantly, one of the MDM2/XIAP inhibitors, MX69, showed minimal inhibitory effect on normal human hematopoiesis in vitro and was very well tolerated in animal models.

Physicochemical Properties

Molecular Formula	C27H26N2O4S
Molecular Weight	474.5713
Exact Mass	474.161
Elemental Analysis	C, 68.33; H, 5.52; N, 5.90; O, 13.48; S, 6.76
CAS #	1005264-47-0
Related CAS #	1005264-47-0
PubChem CID	4075607
Appearance	White to off-white solid powder
LogP	5.2
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	5
Heavy Atom Count	34
Complexity	876
Defined Atom Stereocenter Count	0
InChi Key	XCBONKHCCRJMNW-UHFFFAOYSA-N
InChi Code	InChI=1S/C27H26N2O4S/c1-16-6-11-20(14-17(16)2)29-34(32,33)21-12-13-25-24(15-21)22-4-3-5-23(22)26(28-25)18-7-9-19(10-8-18)27(30)31/h3-4,6-15,22-23,26,28-29H,5H2,1-2H3,(H,30,31)
Chemical Name	4-[8-[(3,4-dimethylphenyl)sulfamoyl]-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-4-yl]benzoic acid
Synonyms	MX69; MX-69; MX 69
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

Targets	MDM2 (Kd = 2.34 μM)
ln Vitro	MX69 prevents the interaction between the MDM2 protein and XIAP RNA, which causes MDM2 to degrade. MX69 is extremely well tolerated in animal models and exhibits a negligible inhibitory effect on normal human hematopoiesis in vitro. In addition to inhibiting the expression of XIAP, MX69-induced MDM2 downregulation also activates p53, which aids in the in vitro apoptosis of cancer cells[1].
ln Vivo	Cancer cell proliferation in vivo is inhibited by MX69-induced MDM2 downregulation, which also activates p53[1].
Enzyme Assay	MX69 is a novel, potent and selective MDM2/XIAP dual inhibitor that may be used to treat cancer. MX69 prevents the interaction between the MDM2 protein and the XIAP RNA, which causes MDM2 to degrade.
Cell Assay	The cytotoxic effect of leads on six ALL cell lines (EU-1, EU-3, EU-6, EU-8, SUP-B13, and UOC-B1) and six NB cell lines (NB-1691, NB-1643, SH-EP1, IMR-32, SK-NSH, and LA1-55N) is determined using the WST assay. Briefly, different lead concentrations are applied to cell cultures in 96-well microtiter plates for a 20-hour period. The optical density is then measured using a microplate reader after the addition of WST (25 mg/well) and an additional 4 hours of incubation.
References	[1]. Discovery of Dual Inhibitors of MDM2 and XIAP for Cancer Treatment. Cancer Cell. 2016 Oct 10;30(4):623-636. [2]. Discovery of Dual Inhibitors of MDM2 and XIAP for Cancer Treatment. Cancer Cell. 2016 Oct 10;30(4):623-636.

Solubility Data

Solubility (In Vitro)

DMSO: ~95 mg/mL (~200.2 mM) Water: <1 mg/mL Ethanol: ~41 mg/mL (~86.4 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.5 mg/mL (5.27 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. 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 (5.27 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.27 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	2.1072 mL	10.5359 mL	21.0717 mL
	5 mM	0.4214 mL	2.1072 mL	4.2143 mL
	10 mM	0.2107 mL	1.0536 mL	2.1072 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.