[2-[[5-[(4-fluorophenyl)carbamoyl]pyrimidin-2-yl]sulfanylmethyl]-4-(trifluoromethoxy)phenyl]boronic acid

[2-[[5-[(4-fluorophenyl)carbamoyl]pyrimidin-2-yl]sulfanylmethyl]-4-(trifluoromethoxy)phenyl]boronic acid Property

Density 

1.53±0.1 g/cm3(Predicted)

storage temp. 

-20°C

solubility 

Soluble in DMSO (>25 mg/ml)

pka

8.18±0.53(Predicted)

form 

solid

color 

Off-white

Stability:

Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.

InChI

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)

InChIKey

SDUDZBCEHIZMFZ-UHFFFAOYSA-N

SMILES

B(C1=CC=C(OC(F)(F)F)C=C1CSC1=NC=C(C(NC2=CC=C(F)C=C2)=O)C=N1)(O)O

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

[2-[[5-[(4-fluorophenyl)carbamoyl]pyrimidin-2-yl]sulfanylmethyl]-4-(trifluoromethoxy)phenyl]boronic acid Chemical Properties,Usage,Production

Description

SX-682 is a novel CXCR1/2 inhibitor (IC50s: CXCR1 = 42 nM, CXCR2 = 20 nM).1?It displayed robust synergistic activity with immune checkpoint blockade against castration resistant prostate cancer.2 It significantly reduced tumor burden in a Ptenfl/fl/Lkb1fl/fl mouse model of lung squamous cell cancer when used in combination with anti-PD1 therapy.3 SX-682 significantly inhibited trafficking of neutrophilic myeloid-derived suppressor cells (PMN-MDSCs) enhancing anti-PD1 immune checkpoint blockade, T cell-based immunotherapy, and NK-cell immunotherapy.4,5

Uses

SX-682 is an orally bioavailable, potent allosteric inhibitor of CXCR1 and CXCR2. SX-682 can block tumor myeloid-derived suppressor cells (MDSCs) recruitment and enhance T cell activation and antitumor immunity[1].

in vivo

IC 50

CXCR1; CXCR2

References

[1] C. BOSS C R. Substituted cyclopentanes, tetrahydrofurans and pyrrolidines as orexin-1-receptor antagonists for treatment of various CNS disorders (WO2015/055994; WO2015/124932; WO2015/124934)[J]. Expert Opinion on Therapeutic Patents, 2016, 26 1: 409-415. DOI:10.1517/13543776.2016.1124087
[2] XIN LU. Effective combinatorial immunotherapy for castration-resistant prostate cancer[J]. Nature, 2017, 543 7647: 728-732. DOI:10.1038/nature21676
[3] JULIA KARGL. Neutrophil content predicts lymphocyte depletion and anti-PD1 treatment failure in NSCLC.[J]. JCI insight, 2019. DOI:10.1172/jci.insight.130850
[4] LILLIAN SUN. Inhibiting myeloid-derived suppressor cell trafficking enhances T cell immunotherapy.[J]. JCI insight, 2019, 4 7. DOI:10.1172/jci.insight.126853
[5] SARAH GREENE. Inhibition of MDSC Trafficking with SX-682, a CXCR1/2 Inhibitor, Enhances NK-Cell Immunotherapy in Head and Neck Cancer Models.[J]. Clinical Cancer Research, 2020: 1420-1431. DOI:10.1158/1078-0432.ccr-19-2625