AC710 mesylate, the mesylate salt of AC710, is a potent, orally bioactive, and selective inhibitor of PDGFR (platelet-derived growth factor receptor) family kinase with Kd values of 0.6, 1.57, 1, 1.3, 1.0 nM for FLT3, CSF1R, KIT, PDGFRα and PDGFRβ, respectively. Because it inhibits PDGFR, AC710 may have anticancer properties. The preclinical development candidate for AC710 was chosen based on the outcomes of a seven-day in vivo tolerability study, a collagen-induced arthritis model, and a mouse tumor xenograft.

Physicochemical Properties

Molecular Formula	C₃₂H₄₆N₆O₇S
Molecular Weight	658.81
Exact Mass	658.315
Elemental Analysis	C, 66.17; H, 7.52; N, 14.94; O, 11.37
CAS #	1351522-05-8
Related CAS #	AC710;1351522-04-7
PubChem CID	54760052
Appearance	Solid powder
LogP	7.425
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	8
Heavy Atom Count	46
Complexity	972
Defined Atom Stereocenter Count	0
SMILES	O=C(C1=NC=C(OC2CC(C)(C)N(CC)C(C)(C)C2)C=C1)NC3=CC=C(NC(NC4=NOC(C(C)(C)C)=C4)=O)C=C3.CS(=O)(O)=O
InChi Key	AUMMSMBRVDYUME-UHFFFAOYSA-N
InChi Code	InChI=1S/C31H42N6O4.CH4O3S/c1-9-37-30(5,6)17-23(18-31(37,7)8)40-22-14-15-24(32-19-22)27(38)33-20-10-12-21(13-11-20)34-28(39)35-26-16-25(41-36-26)29(2,3)4;1-5(2,3)4/h10-16,19,23H,9,17-18H2,1-8H3,(H,33,38)(H2,34,35,36,39);1H3,(H,2,3,4)
Chemical Name	N-[4-[(5-tert-butyl-1,2-oxazol-3-yl)carbamoylamino]phenyl]-5-(1-ethyl-2,2,6,6-tetramethylpiperidin-4-yl)oxypyridine-2-carboxamide;methanesulfonic acid
Synonyms	AC 710 Mesylate; AC710 Mesylate; AC-710 Mesylate
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	PDGFRα (Kd = 1.3 nM); PDGFRβ (Kd = 1 nM); c-Kit (Kd = 1 nM); FLT3 (Kd = 0.6 nM); CSF1R (Kd = 1.57 nM)
ln Vitro	AC710 is a potent, orally active, and selective inhibits the PDGFR (platelet-derived growth factor receptor) family kinase, with Kd values of 0.6, 1.57, 1, 1.3, and 1.0 nM for FLT3, CSF1R, KIT, PDGFRα, and PDGFRβ, individually. AC710 may have anticancer properties because it is a PDGFR inhibitor. The preclinical development candidate AC710 was chosen based on outcomes from a rat in vivo tolerability study, a mouse tumor xenograft, and a collagen-induced arthritis model.
ln Vivo	AC710 shows a dose-dependent effect on disease in a mouse model of collagen-induced arthritis (CIA), starting at a dose of 3 mg/kg and lasting for 15 days (days 0–14). When given at a safe dosage, dexomethasone reduces joint swelling and inflammation more effectively than AC710, either equally or marginally better. At the tested doses, AC710 is well tolerated[1]. Tumor growth is momentarily stopped at 0.3 mg/kg of AC710, but it soon resumes. Tumors fully regress at 3 and 30 mg/kg of AC710, and the tumor volume remains suppressed long after dosing is stopped. Animals treated with AC710 at all doses show no signs of body weight loss, suggesting that mice can tolerate it well at effective dosages.
Enzyme Assay	AC710 is a potent, orally active, and selective inhibits the PDGFR (platelet-derived growth factor receptor) family kinase, with Kd values of 0.6, 1.57, 1, 1.3, and 1.0 nM for FLT3, CSF1R, KIT, PDGFRα, and PDGFRβ, individually.
Animal Protocol	Mice: The MV4-11cell line is used in a subcutaneous flank-tumor xenograft model in athymic nude mice to evaluate the antitumor efficacy of AC710. For two weeks, the dosage of AC710 is 0.3, 3, and 30 mg/kg. Growth of the tumor and body weight are tracked.
References	[1]. Discovery of AC710, a Globally Selective Inhibitor of Platelet-Derived Growth Factor Receptor-Family Kinases. ACS Med Chem Lett. 2012 Sep 24;3(12):997-1002.

Solubility Data

Solubility (In Vitro)	DMSO: 10 mM Water: <1 mg/mL Ethanol: N/A
Solubility (In Vivo)	O=C(C1=NC=C(OC2CC(C)(C)N(CC)C(C)(C)C2)C=C1)NC3=CC=C(NC(NC4=NOC(C(C)(C)C)=C4)=O)C=C3. CS(=O)(O)=O  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.5179 mL	7.5894 mL	15.1789 mL
	5 mM	0.3036 mL	1.5179 mL	3.0358 mL
	10 mM	0.1518 mL	0.7589 mL	1.5179 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.