Ladarixin sodium (DF 2156A), an investigational small-molecule drug, is a potent, orally bioavailable, non-competitive, dual allosteric inhibitor of CXCR1 and CXCR2 interleukin-8 (IL-8A and IL-8B, respectively). In preclinical studies, ladarixin was shown to prevent and reverse diabetes in NOD mice. The potency of CXCR1/2 inhibition may prevent inflammation- and autoimmunity-mediated damage of pancreatic islets. CXCR1/2 inhibition blocks and reverses type 1 diabetes in mice.

Physicochemical Properties

Molecular Formula	C11H11F3NNAO6S2
Molecular Weight	397.323122262955
Exact Mass	396.987
CAS #	865625-56-5
Related CAS #	Ladarixin;849776-05-2
PubChem CID	23709380
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	5
Heavy Atom Count	24
Complexity	630
Defined Atom Stereocenter Count	1
SMILES	C[C@H](C1=CC=C(C=C1)OS(=O)(=O)C(F)(F)F)C(=O)[N-]S(=O)(=O)C.[Na+]
InChi Key	QICAUCDBOAKDNS-OGFXRTJISA-M
InChi Code	InChI=1S/C11H12F3NO6S2.Na/c1-7(10(16)15-22(2,17)18)8-3-5-9(6-4-8)21-23(19,20)11(12,13)14/h3-7H,1-2H3,(H,15,16)/q+1/p-1/t7-/m1./s1
Chemical Name	sodium (R)-(methylsulfonyl)(2-(4-(((trifluoromethyl)sulfonyl)oxy)phenyl)propanoyl)amide
Synonyms	DF-2156A DF2156A DF 2156A DF-2156 DF2156 DF 2156
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	Human polymorphonuclear leukocytes (PMN) are inhibited in their migration to CXCL8 (IC50 0.7 nM) by ladararixin [2].
ln Vivo	In a single OVA exposure scenario, ladararixin (10 mg/kg; oral, once daily) decreases allergic airway inflammation. In a chronic OVA exposure model, ladararixin decreases bronchial hyperresponsiveness, remodeling, and allergic airway inflammation [1]. Ladararixin (10 mg/kg; orally, once day for 8 days) decreases the fibrosis and inflammation of the lungs caused by bleomycin in mice [1]. Ladararixin (10 mg/kg; once daily, oral) prevents mice's influenza A infection from getting worse when exposed to cigarette smoke [1]. Additionally, ladararixin successfully lowers polymorphonuclear leukocyte infiltration generated by CXCL8 in a number of animal models without significantly lowering systemic neutrophil numbers in a dose-related manner [2].
Animal Protocol	Animal/Disease Models: Mouse (cigarette smoke induced exacerbation model of influenza A infection) [1] Doses: 10 mg/kg Route of Administration: Oral one time/day on days 2, 3 and 4 after infection Experimental Results: Dramatically attenuated exacerbation of lethality and respiratory changes noted in the CSFlu group.
References	[1]. CXCR1 and CXCR2 Inhibition by Ladarixin Improves Neutrophil-Dependent Airway Inflammation in Mice. Front Immunol. 2020 Oct 2;11:566953. [2]. Ladarixin, a dual CXCR1/2 inhibitor, attenuates experimental melanomas harboring different molecular defects by affecting malignant cells and tumor microenvironment. Oncotarget. 2017 Feb 28;8(9):14428-14442.
Additional Infomation	Ladarixin Sodium is the sodium salt form of ladarixin, an orally bioavailable, small molecule, dual inhibitor of C-X-C motif chemokine receptors 1 (CXCR1) and 2 (CXCR2), with potential anti-inflammatory and antineoplastic activities. Upon oral administration, ladarixin selectively targets and allosterically binds to CXCR 1 and 2, thereby preventing CXCR1 and CXCR2 activation by their ligand and pro-inflammatory chemokine interleukin 8 (IL-8 or CXCL8). This inhibits CXCR1/2-mediated signaling, which inhibits inflammatory processes, reduces both the recruitment and migration of immunosuppressive myeloid-derived suppressor cells (MDSCs) and neutrophils in the tumor microenvironment (TME), 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, and 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, resistance to chemotherapeutic agents and myeloid cell suppression. They also play a key role in inflammation and their expression is elevated in several inflammatory-driven diseases.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~251.69 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.29 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 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 (6.29 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 (6.29 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	2.5169 mL	12.5843 mL	25.1686 mL
	5 mM	0.5034 mL	2.5169 mL	5.0337 mL
	10 mM	0.2517 mL	1.2584 mL	2.5169 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.