SX-682 (SX682) is a novel boronic acid-containing and selective CXCR2 chemokine receptor antagonist with potential anticancer and immunomodulatory activities. The proliferation and progression of tumor cells are facilitated by the upregulation of the CXC chemokine receptor CXCR2 in a range of distinct tumor cell types. Reduced tumorigenesis and metastasis were the results of CXCR2 inhibition. SX-682 is a CXCR2 antagonist that may be used to treat melanoma and prostate cancer that is resistant to castration. Syntrix Biosystems, Inc. has initiated a phase I clinical trial combining SX-682 and pembrolizumab for the treatment of metastatic melanoma.

Physicochemical Properties

Molecular Formula	C19H14BF4N3O4S
Molecular Weight	467.20
Exact Mass	467.07
Elemental Analysis	C, 48.85; H, 3.02; B, 2.31; F, 16.27; N, 8.99; O, 13.70; S, 6.86
CAS #	1648843-04-2
Related CAS #	1648843-04-2
PubChem CID	90467234
Appearance	Off-white to light yellow solid powder
Density	1.53±0.1 g/cm3(Predicted)
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	11
Rotatable Bond Count	7
Heavy Atom Count	32
Complexity	606
Defined Atom Stereocenter Count	0
SMILES	S(C1N=CC(=CN=1)C(NC1C=CC(=CC=1)F)=O)CC1C=C(C=CC=1B(O)O)OC(F)(F)F
InChi Key	SDUDZBCEHIZMFZ-UHFFFAOYSA-N
InChi Code	InChI=1S/C19H14BF4N3O4S/c21-13-1-3-14(4-2-13)27-17(28)12-8-25-18(26-9-12)32-10-11-7-15(31-19(22,23)24)5-6-16(11)20(29)30/h1-9,29-30H,10H2,(H,27,28)
Chemical Name	[2-[[5-[(4-fluorophenyl)carbamoyl]pyrimidin-2-yl]sulfanylmethyl]-4-(trifluoromethoxy)phenyl]boronic acid
Synonyms	SX682; SX 682; SX-682
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	CXCR2; CXCR1
ln Vitro	In vitro activity: SX-682 is a brand-new, highly effective, and selective CXCR2 chemokine receptor antagonist that may have anticancer effects. The proliferation and progression of tumor cells are facilitated by the upregulation of the CXC chemokine receptor CXCR2 in a range of distinct tumor cell types. Reduced tumorigenesis and metastasis were the results of CXCR2 inhibition. SX-682 is a CXCR2 antagonist that may be used to treat melanoma and prostate cancer that is resistant to castration. Syntrix Biosystems, Inc. has initiated a phase I clinical trial combining SX-682 and pembrolizumab for the treatment of metastatic melanoma.
ln Vivo	In vivo, the whole tumor accumulation of CXCL1 in MOC1 and LLC tumors is notably higher than in normal lung and oral mucosa, respectively, and is not reduced by SX-682 treatment. In both models, tumor-bearing mice exhibit higher plasma accumulation of CXCL1 than naive mice, and this accumulation increases after SX-682 treatment. SX-682 treatment of mice with MOC1 or LLC tumors starting 10 or 20 days after the tumor initiation does not change the expression of CXCR1 or CXCR2 on tumor cells in vivo. [2] Tumor PMN-MDSC expression of the genes that produce H2O2, superoxide dismutase 1/2 or cell surface TGF-β, is not significantly changed after receiving in vivo SX-682 treatment. [3]
Animal Protocol	wild-type C57BL/6 mice subcutaneously injected with MOC2 cells (1x105 cells in PBS) 500 mg/kg Oral gavage
References	[1]. Nature . 2017 Mar 30;543(7647):728-732. [2]. JCI Insight . 2019 Apr 4;4(7):e126853. [3]. Clin Cancer Res . 2020 Mar 15;26(6):1420-1431.
Additional Infomation	CXCR1/2 Inhibitor SX-682 is an orally bioavailable, selective and reversible antagonist of C-X-C motif chemokine receptors 1 (CXCR1) and 2 (CXCR2), with potential anti-inflammatory and antineoplastic activities. Upon administration CXCR1/2 inhibitor SX-682 selectively and allosterically binds to CXCR 1 and 2 and inhibits their activation by tumor-secreted chemokines. This inhibits CXCR1/2-mediated signaling, reduces both recruitment and migration of immunosuppressive myeloid-derived suppressor cells (MDSCs) and neutrophils in the tumor microenvironment (TME), inhibits inflammatory processes and abrogates the immunosuppressive-induced nature of the TME. This allows effector cells, such as natural killer (NK) cells and cytotoxic T-lymphocytes (CTLs), to kill and eliminate cancer cells. This inhibits tumor cell migration, metastasis, angiogenesis and tumor cell proliferation. CXCR1 and 2, G protein-coupled receptor proteins located on myeloid cells and certain tumor cells, play key roles in the immunosuppressive nature of the TME, tumor metastasis, therapy-resistance and myeloid cell suppression. They play a key role in inflammation and their expression is elevated in several inflammatory-driven diseases.

Solubility Data

Solubility (In Vitro)

DMSO: 93~250 mg/mL (199.1~535.1 mM) Water: <1 mg/mL Ethanol: <1 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: 11.76 mg/mL (25.17 mM) in 15% Cremophor EL + 85% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication (<60°C). Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.45 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 20.8 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	2.1404 mL	10.7021 mL	21.4041 mL
	5 mM	0.4281 mL	2.1404 mL	4.2808 mL
	10 mM	0.2140 mL	1.0702 mL	2.1404 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.