XL-784 is a selective inhibitor of MMP. Its IC50s for MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, and MMP-13 are about 1900, 0.81, 120, and 10.8 respectively. ,18,0.56 nM.

Physicochemical Properties

Molecular Formula	C21H22CLF2N3O8S
Molecular Weight	549.929490566254
Exact Mass	549.078
CAS #	1224964-36-6
Related CAS #	XL-784 free base;1356992-21-6
PubChem CID	74439626
Appearance	White to off-white solid powder
LogP	1.8
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	9
Heavy Atom Count	36
Complexity	847
Defined Atom Stereocenter Count	0
SMILES	ClC1C=CC(=CC=1)OC1=C(C=C(C=C1F)S(N1CCN(C(=O)OCCOC)CC1C(NO)=O)(=O)=O)F
InChi Key	PRIJGYZAOBNIPH-UHFFFAOYSA-N
InChi Code	InChI=1S/C21H22ClF2N3O8S/c1-33-8-9-34-21(29)26-6-7-27(18(12-26)20(28)25-30)36(31,32)15-10-16(23)19(17(24)11-15)35-14-4-2-13(22)3-5-14/h2-5,10-11,18,30H,6-9,12H2,1H3,(H,25,28)
Chemical Name	2-methoxyethyl 4-[4-(4-chlorophenoxy)-3,5-difluorophenyl]sulfonyl-3-(hydroxycarbamoyl)piperazine-1-carboxylate
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

ln Vitro	XL-784 is a highly powerful, low molecular weight (1,122 g/mol) MMP inhibitor with very poor water solubility (20 μg/mL). XL-784 potently inhibits MMP-2, MMP-13 and ADAM10 [TNF-alpha converting enzyme (TACE)] activities in vitro with IC50 values in the range of 1-2 nM. XL-784 also suppresses MMP-9 (IC50 ~20 nM) activity and ADAM17 (IC50 ~70 nM) also known as TACE. However, its inhibitory effectiveness against MMP-1 is low (IC50 ~2,000 nM)[1].
ln Vivo	Every mouse responded to therapy in a similar way. Aneurysms formed in all control animals; the average percentage of ΔAD was 158.5%±4.3%. The doxycycline therapy and all XL-784 dosages effectively prevented aortic dilatation. Reduced aortic dilatation at harvest was directly correlated with XL-784 dose-response ratios of 50 mg/kg 140.4% ±3.2%; 125 mg/kg 129.3% ±5.1%; 250 mg/kg 119.2% ±3.5%; and 250 mg/kg 119.2% ±3.5%). When compared to the control, all Ps<0.01. At higher doses (375 mg/kg 88.6% ± 4.4%; 500 mg/kg 76.0% ± 3.5%), this pattern persisted. When it came to preventing maximal aortic dilatation following elastase infusion, the two highest dosages of XL-784 that were tested out performed effectively (112.2% ± 2.0%, P < 0.05) [2].
References	[1]. Evaluation of metalloprotease inhibitors on hypertension and diabetic nephropathy. Am J Physiol Renal Physiol. 2011 Apr;300(4):F983-98. [2]. Effect of novel limited-spectrum MMP inhibitor XL784 in abdominal aortic aneurysms. J Cardiovasc Pharmacol Ther. 2012 Dec;17(4):417-26.

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 110 mg/mL (~200.39 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.75 mg/mL (5.01 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 27.5 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: ≥ 2.75 mg/mL (5.01 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 27.5 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: ≥ 2.75 mg/mL (5.01 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 27.5 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	1.8184 mL	9.0921 mL	18.1841 mL
	5 mM	0.3637 mL	1.8184 mL	3.6368 mL
	10 mM	0.1818 mL	0.9092 mL	1.8184 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.