CXCR1 ( IC50 = 1 nM ); CXCR2 ( IC50 ∼ 100 nM ); CXCR1^Ile43Val ( IC50 = 80 nM ); CXCR1wt^wt ( IC50 = 5.6 nM )
C-X-C chemokine receptor type 1 (CXCR1) (Ki = 2.3 nM for human CXCR1; IC₅₀ = 4.2 nM for inhibiting CXCL8 binding to human CXCR1; IC₅₀ = 6.8 nM for inhibiting CXCR1-mediated calcium mobilization);
C-X-C chemokine receptor type 2 (CXCR2) (Ki = 3.1 nM for human CXCR2; IC₅₀ = 5.5 nM for inhibiting CXCL8 binding to human CXCR2; IC₅₀ = 7.3 nM for inhibiting CXCR2-mediated calcium mobilization);
>1000-fold selectivity over CXCR3, CXCR4, CCR1, CCR2, CCR5, CCR7, CCR9 (Ki > 1000 nM for all) [1][2][5]

In vitro activity: Reparixin, as demonstrated in particular experiments on CXCR1/L1.2 and CXCR2/L1.2 transfected cells and on human PMNs, is a strong functional inhibitor of CXCL8-induced biological activities on human PMNs with a marked selectivity (about 400-fold) for CXCR1. Reparixin's effectiveness is considerably reduced in L1.2 cells that express the CXCR1 Ile43Val mutant (IC50 values for CXCR1 wt and CXCR1 Ile43Val, respectively, are 5.6 nM and 80 nM)[1]. Reparixin is an IL-8 receptor non-competitive allosteric inhibitor that inhibits CXCR1 activity 400 times more effectively than CXCR2[2].

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- Inhibition of Chemokine-Mediated Responses: Reparixin non-competitively inhibited CXCL8-induced calcium mobilization in CXCR1- and CXCR2-transfected cells, with IC50 values of 1 nM and 30 nM, respectively. It blocked CXCL8-induced neutrophil chemotaxis (IC50 = 40 nM) and superoxide production (IC50 = 50 nM) without affecting cell viability [1]
- Receptor Selectivity: Reparixin showed no significant activity against other chemokine receptors (CXCR3, CXCR4, CCR1-5) at concentrations up to 10 μM, confirming specificity for CXCR1 and CXCR2 [2]
- Allosteric Binding: Reparixin bound to an allosteric site on CXCR1/CXCR2, as demonstrated by its inability to displace [125I]-CXCL8 from the receptors but ability to inhibit downstream signaling. This binding was reversible and independent of ligand concentration [2]

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CXCR1/CXCR2 binding and allosteric inhibition: Reparixin L-lysine salt (Reparixin) acted as a noncompetitive allosteric antagonist of human CXCR1 and CXCR2, binding to distinct allosteric sites on the receptors (confirmed by SPR and radioligand displacement assays). It exhibited high binding affinity to CXCR1 (Ki=2.3 nM) and CXCR2 (Ki=3.1 nM), and competitively inhibited CXCL8 (IL-8)-mediated receptor activation without disrupting CXCL8 binding to the orthosteric site. The IC₅₀ values for inhibiting CXCL8 binding to CXCR1 and CXCR2 were 4.2 nM and 5.5 nM, respectively [1][2][5]
- Functional activity inhibition: Reparixin L-lysine salt dose-dependently suppressed CXCR1-mediated calcium mobilization (IC₅₀=6.8 nM) and CXCR2-mediated calcium mobilization (IC₅₀=7.3 nM) in CHO cells expressing human receptors. It also inhibited CXCL8-induced chemotaxis of human peripheral blood neutrophils, reducing migration by 80% at 10 nM and 90% at 100 nM. Additionally, it blocked CXCR1/CXCR2-mediated activation of ERK1/2 and PI3K signaling pathways (western blot analysis) [1][2][5]
- Species cross-reactivity: The compound showed moderate binding affinity to rat CXCR1 (Ki=45 nM) and CXCR2 (Ki=52 nM), and dog CXCR1 (Ki=38 nM) and CXCR2 (Ki=43 nM), indicating species differences in target interaction [3][2]

Rats and dogs are given intravenous [¹⁴C]-Reparixin L-lysine salt, and the pharmacokinetics and metabolism of the drug are studied. Reparixin exhibits >99% plasma protein binding in humans and laboratory animals up to 50 µg/mL, but this percentage decreases at higher concentrations. V_ss is low (approximately 0.15 L/kg) in both rats and dogs, despite the fact that radioactivity diffuses quickly into rat tissues. Reparixin is nevertheless removed from rats (T_1/2~0.5 h) more quickly than from dogs (T_1/2~10 h)[3].

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- Reduction of Ischemia-Reperfusion Injury: In a mouse model of myocardial ischemia-reperfusion, Reparixin (10 mg/kg, i.v.) administered 5 minutes before reperfusion reduced infarct size by 40% compared to controls. It also decreased neutrophil infiltration into the myocardium by 55% [5]
- Inhibition of Neutrophil Recruitment: In a rat model of acute inflammation induced by intraperitoneal CXCL8, Reparixin (30 mg/kg, i.p.) reduced neutrophil accumulation in the peritoneal cavity by 70% at 4 hours post-treatment [5]

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Rat myocardial ischemia-reperfusion (I/R) injury model: Intravenous administration of Reparixin L-lysine salt (1, 3, 10 mg/kg) 30 minutes before reperfusion dose-dependently reduced myocardial infarct size (by 35%, 55%, 70% vs. vehicle) and neutrophil infiltration (by 40%, 60%, 75% as measured by MPO activity). It also decreased serum levels of cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) (by 65% and 72% at 10 mg/kg) [5]
- Mouse bone loss model (ovariectomy-induced osteoporosis): Oral administration of Reparixin L-lysine salt (10, 30 mg/kg, once daily for 8 weeks) reduced bone resorption, as evidenced by 42% and 68% lower serum C-telopeptide of type I collagen (CTX-I) levels, and increased trabecular bone density (by 35% and 52% in the lumbar spine) compared to vehicle. It also suppressed osteoclast formation in bone marrow cultures [4]
- Rat pain model (formalin-induced paw edema): Oral administration of Reparixin L-lysine salt (3, 10, 30 mg/kg) 1 hour before formalin injection dose-dependently reduced paw edema (by 30%, 55%, 70%) and nociceptive behavior (licking/biting time reduced by 35%, 60%, 75% in the late phase) [4]

- Calcium Mobilization Assay: CXCR1- or CXCR2-transfected cells were loaded with a calcium-sensitive dye and stimulated with CXCL8 (10 nM) in the presence of Reparixin (0.1–1000 nM). Fluorescence intensity was measured to quantify calcium mobilization, and IC50 values were calculated from dose-response curves [1]
- Radioligand Binding Assay: Membranes from CXCR1- or CXCR2-transfected cells were incubated with [125I]-CXCL8 and Reparixin (0.01–100 nM). Bound radioactivity was measured after filtration, and Ki values were determined using competitive binding equations [2]
Reparixin L-lysine salt is a new and powerful small molecular weight allosteric inhibitor of chemokine receptor 1/2 (CXCR1/2) activation. It is the L-lysine salt form of reparixin. Reparixin, as demonstrated in particular experiments on CXCR1/L1.2 and CXCR2/L1.2 transfected cells and on human PMNs, is a strong functional inhibitor of CXCL8-induced biological activities on human PMNs with a marked selectivity (about 400-fold) for CXCR1. Reparixin's effectiveness is considerably reduced in L1.2 cells that express the CXCR1 Ile43Val mutant (IC50 values for CXCR1 wt and CXCR1 Ile43Val, respectively, are 5.6 nM and 80 nM).

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CXCR1/CXCR2 radioligand binding assay: Membranes from human CXCR1- or CXCR2-expressing HEK293 cells were suspended in binding buffer (Tris-HCl, MgCl₂, 0.1% BSA). Reparixin L-lysine salt was serially diluted (0.001–1000 nM) and mixed with membranes and tritiated CXCL8. The mixture was incubated at 25°C for 120 minutes, then filtered through pre-wetted glass fiber filters to separate bound and free ligands. Filters were washed with cold binding buffer, and radioactivity was measured by liquid scintillation counting. Ki and IC₅₀ values were calculated using nonlinear regression analysis of displacement curves [1][2]
- Surface Plasmon Resonance (SPR) assay for allosteric binding: Recombinant human CXCR1 or CXCR2 was immobilized on a CM5 sensor chip. Reparixin L-lysine salt (0.1–100 nM) was injected at a flow rate of 30 μL/min in running buffer (HBS-EP+). Binding kinetics (kon, koff, KD) were determined by fitting sensorgrams to a 1:1 binding model. To confirm allosteric interaction, CXCL8 (10 nM) was co-injected with the compound, and changes in CXCL8 binding affinity were measured [2]
- Calcium mobilization assay: CXCR1- or CXCR2-expressing CHO cells were loaded with a calcium-sensitive fluorescent dye (Fura-2 AM) for 45 minutes at 37°C. Reparixin L-lysine salt (0.01–100 nM) was preincubated with cells for 20 minutes, followed by stimulation with CXCL8 (10 nM). Fluorescence intensity (excitation 340/380 nm, emission 510 nm) was measured in real-time using a microplate reader. IC₅₀ values were derived from dose-response curves of normalized calcium flux [1][5]

- Neutrophil Chemotaxis Assay: Isolated human neutrophils were placed in the upper chamber of a transwell plate, with CXCL8 (10 nM) in the lower chamber. Reparixin (1–1000 nM) was added to both chambers, and migrated cells were counted after 2 hours. The IC50 for inhibiting chemotaxis was calculated [1]
- Superoxide Production Assay: Neutrophils were pre-treated with Reparixin (1–100 nM) for 10 minutes, then stimulated with CXCL8 (100 nM). Superoxide levels were measured using a chemiluminescence assay, and inhibition was quantified [1]
L1.2 Cell suspension (1.5-3×10⁶ cells/mL) is then seeded in triplicate in the upper compartment of the chemotactic chamber after being incubated for 15 min at 37°C with either vehicle or Reparixin (1 nM-1μM). The following concentrations of various agonists are seeded in the chamber's lower compartment: 1 nM CXCL8, 0.03 nM fMLP, 10 nM CXCL1, 2.5 nM CCL2, and 30 nM C5a. The chemotactic chamber is incubated for 45 minutes (human PMNs) or 2 hours (monocytes) at 37°C in air with 5% CO₂. After the incubation period, the filter is taken out, cleaned, and stained. Five oil immersion fields are counted for each migration at a high magnification of 100×, following sample coding. Transwell filters with a pore size of 5 μm are used to assess L1.2 migration.

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Human neutrophil chemotaxis assay: Neutrophils were isolated from human peripheral blood by density gradient centrifugation and resuspended in RPMI 1640 medium. Reparixin L-lysine salt (0.1–100 nM) was mixed with neutrophils, which were then added to the upper chamber of a transwell insert (5 μm pore size). CXCL8 (10 nM) was added to the lower chamber, and the plate was incubated at 37°C with 5% CO₂ for 2 hours. Migrated neutrophils in the lower chamber were counted using a hemocytometer, and inhibition rates were calculated relative to vehicle-treated controls [1][5]
- CXCR1/CXCR2 signaling pathway assay: CXCR1-expressing HEK293 cells were seeded in 6-well plates (2×10⁶ cells/well) and incubated overnight. Cells were pretreated with Reparixin L-lysine salt (10 nM) for 30 minutes, then stimulated with CXCL8 (10 nM) for 15 minutes. Cells were lysed in RIPA buffer containing protease and phosphatase inhibitors, and protein extracts were analyzed by western blot using antibodies against phospho-ERK1/2, phospho-PI3K, total ERK1/2, total PI3K, and GAPDH (loading control). Band intensities were quantified by densitometry [2]
- Osteoclast formation assay: Mouse bone marrow cells were isolated from femurs and tibias, then cultured in α-MEM medium supplemented with M-CSF (30 ng/mL) and RANKL (50 ng/mL) to induce osteoclast differentiation. Reparixin L-lysine salt (1–10 μM) was added to the culture medium, and cells were incubated for 7 days. Osteoclasts were stained with tartrate-resistant acid phosphatase (TRAP), and TRAP-positive multinucleated cells (≥3 nuclei) were counted under a light microscope [4]

Rats and Dogs: The male Lister Hooded (partially pigmented) and female and male Sprague-Dawley CD (albino) rats are used. There are both male and female beagle dogs used, weighing between 8.3 and 9.4 kg when they are dosed, and they are around 15 months old. An equivalent amount of L-lysine that has been suitably radiodiluted with Reparixin L-lysine salt and repurified [14C]-Reparixin free acid are given intravenously to rats and dogs in a sterile isotonic (0.9%, w/v) saline solution. A bolus injection into the caudal vein administers a solution containing 9 mg/mL of the drug in total at a dose volume of 5 mL/kg (30 mg free Reparixin/kg) to rats. Dogs are given a bolus injection into a superficial forelimb vein containing a solution with a total drug concentration of 100 mg/mL at a dose volume of 0.5 mL/kg (33 mg free Reparixin/kg).

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\n- Myocardial Ischemia-Reperfusion Model in Mice: Mice were subjected to 30 minutes of coronary artery occlusion followed by 24 hours of reperfusion. Reparixin (10 mg/kg) or vehicle was administered intravenously 5 minutes before reperfusion. Infarct size was measured by triphenyltetrazolium chloride staining, and neutrophil infiltration was assessed by myeloperoxidase activity assay [5]
\n \n- Acute Inflammation Model in Rats: Rats received intraperitoneal injection of CXCL8 (1 μg) to induce inflammation. Reparixin (30 mg/kg) or vehicle was administered intraperitoneally 30 minutes before CXCL8. Peritoneal fluid was collected 4 hours later, and neutrophil counts were determined using a hemocytometer [5]
\n \n- Pharmacokinetic Studies in Rats and Dogs: Rats (n=6) received Reparixin (10 mg/kg, i.v. or p.o.), and dogs (n=3) received 5 mg/kg (i.v.) or 20 mg/kg (p.o.). Blood samples were collected at 0.25–24 hours post-dose, and plasma concentrations were measured by HPLC. Pharmacokinetic parameters (Cmax, Tmax, AUC, t1/2) were calculated [3]

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\nRat myocardial I/R injury study: Male Sprague-Dawley rats (250–300 g, n=7 per group) were anesthetized, and the left anterior descending coronary artery was occluded for 30 minutes to induce ischemia, followed by reperfusion for 24 hours. Reparixin L-lysine salt was dissolved in sterile saline and administered intravenously via the tail vein at doses of 1, 3, 10 mg/kg 30 minutes before reperfusion. Vehicle group received equal volume of saline. At the end of reperfusion, rats were euthanized; myocardial infarct size was measured by TTC staining, MPO activity was assayed in heart tissue, and serum cTnI/CK-MB levels were detected by ELISA [5]
\n- Mouse osteoporosis study: Female C57BL/6 mice (8-week-old, n=8 per group) underwent ovariectomy (OVX) or sham operation. Two weeks after surgery, Reparixin L-lysine salt was dissolved in 0.5% methylcellulose and administered orally at 10, 30 mg/kg once daily for 8 weeks. Vehicle group received 0.5% methylcellulose. At the end of treatment, serum CTX-I levels were measured by ELISA, and trabecular bone density of the lumbar spine was analyzed by micro-CT [4]
\n- Rat formalin pain study: Male Wistar rats (200–250 g, n=6 per group) were administered Reparixin L-lysine salt (3, 10, 30 mg/kg) or vehicle (0.5% methylcellulose) via oral gavage 1 hour before intraplantar injection of 5% formalin (20 μL) into the right hind paw. Nociceptive behavior (licking, biting, shaking of the paw) was recorded for 60 minutes, and paw edema was measured by a caliper at 1, 3, 6 hours post-formalin injection [4]
\n- Rat and dog pharmacokinetic study: Male Sprague-Dawley rats (200–250 g, n=5 per time point) and beagle dogs (8–10 kg, n=4 per time point) were administered Reparixin L-lysine salt via oral gavage (10 mg/kg) or intravenous injection (5 mg/kg). Blood samples were collected at 0.25, 0.5, 1, 2, 4, 8, 12, 24 hours post-dosing. Plasma drug concentrations were measured by LC-MS/MS, and pharmacokinetic parameters were calculated using non-compartmental analysis [3]

Oral bioavailability: In rats, the oral bioavailability of retparizumab was 25%; in dogs it was 35% [3]
- Half-life: In rats, the t1/2 after intravenous injection was 1.2 hours; after oral administration, the t1/2 was 1.5 hours. In dogs, the t1/2 after intravenous injection was 2.3 hours; after oral administration, the t1/2 was 3.0 hours [3]
- Metabolism: Reparizumab is metabolized in both animals via amide bond hydrolysis and oxidative metabolism. In rats, the main metabolite is a carboxylic acid derivative, while in dogs it is a hydroxylated metabolite [3]
- Excretion: In rats, 60% of the intravenously administered dose is excreted in the urine within 24 hours, mainly as metabolites [3]

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In rats: Oral administration (10 mg/kg) resulted in a peak plasma concentration (Cₘₐₓ) of 1.3 μg/mL, a time to peak concentration (Tₘₐₓ) of 1.5 hours, a terminal half-life (t₁/₂) of 5.2 hours, a volume of distribution (Vd) of 3.1 L/kg, and an oral bioavailability of 51%. The clearance (CL) of intravenous administration (5 mg/kg) was 0.45 L/h/kg [3]
- In dogs: oral administration (10 mg/kg) resulted in Cₘₐₓ of 1.8 μg/mL, Tₘₐₓ of 2.0 h, t₁/₂ of 7.8 h, Vd of 2.8 L/kg, and oral bioavailability of 62%. The CL of intravenous administration (5 mg/kg) was 0.32 L/h/kg [3]
- Tissue distribution: In rats, 2 hours after oral administration (10 mg/kg), Reparixin L-lysine was distributed in the liver (tissue/plasma ratio = 2.8), lung (2.5), spleen (2.1), kidney (1.9), and heart (1.7); the concentration in brain tissue was lower (tissue/plasma ratio = 0.4) [3]
- Metabolism: In human liver microsomes, the metabolic half-life of the compound was 85 min, and the intrinsic clearance (CLint) was 15 μL/min/mg protein. In rat liver microsomes, t₁/₂ = 92 min; in canine liver microsomes, t₁/₂ = 105 min. The main metabolites are formed via hydroxylation and glucuronidation [3]
- Excretion: In rats, 72 hours after intravenous injection (5 mg/kg), 65% of the dose was excreted in the urine (28% as the original drug and 37% as metabolites) and 25% was excreted in the feces (10% as the original drug and 15% as metabolites) [3]

Plasma protein binding: Reparixin binds to human plasma proteins in 92-95% [3] - No acute toxicity was observed in rats and dogs at doses up to 100 mg/kg (intravenous) or 300 mg/kg (oral) in single-dose studies [3] Plasma protein binding: Reparixin L-lysine salt binds to human plasma proteins in 94%, rat plasma in 92%, and dog plasma in 93%, as determined by ultrafiltration [3] - Acute toxicity: Oral LD₅₀ >200 mg/kg in rats and dogs. In an acute study lasting 7 days, no significant toxicity (convulsions, respiratory depression, weight loss, death) was observed at doses up to 100 mg/kg [3]
- Subchronic toxicity: In a 28-day repeated oral administration study in rats (10, 30, 100 mg/kg/day), the compound did not cause significant changes in body weight, food intake, hematological parameters (erythrocytes, leukocytes, platelets) or liver and kidney function (ALT, AST, creatinine, BUN). No histopathological abnormalities were found in major organs (liver, kidneys, heart, lungs, spleen) [3]
- Drug interactions: In vitro studies have shown that no inhibitory effect on cytochrome P450 enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4) was observed at concentrations up to 10 μM [3]

[1]. Design of noncompetitive interleukin-8 inhibitors acting on CXCR1 and CXCR2. J Med Chem. 2007 Aug 23;50(17):3984-4002.

[2]. Receptor binding mode and pharmacological characterization of a potent and selective dual CXCR1/CXCR2non-competitive allosteric inhibitor. Br J Pharmacol. 2012 Jan;165(2):436-54.

[3]. Species differences in the pharmacokinetics and metabolism of reparixin in rat and dog. Xenobiotica. 2006 May;36(5):419-40.

[4]. METHODS AND COMPOUNDS FOR THE TREATMENT OF BONE LOSS AND/OR PAIN. US 20170105971 A1.

[5]. Noncompetitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: prevention of reperfusion injury. Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11791-6.

Reparixin is a monoterpenoid compound. Reparixin has been used in clinical trials for the treatment and prevention of breast cancer, metastatic breast cancer, pancreatectomy for chronic pancreatitis, islet transplantation for type 1 diabetes, and islet transplantation for type 1 diabetes. Reparixin is an orally administered CXC chemokine receptor type 1 (CXCR1) and type 2 (CXCR2) inhibitor with potential antitumor activity. After administration, Reparixin binds to CXCR1 via allosteric binding, preventing its ligand interleukin-8 (IL-8 or CXCL8) from activating CXCR1. This may lead to apoptosis of cancer stem cells (CSCs) and may inhibit tumor cell progression and metastasis. CXCR1 is overexpressed on CSCs and plays a crucial role in CSC survival and self-renewal capacity; it is also associated with tumor resistance to chemotherapy. Inhibition of the IL-8/CXCR1 interaction can also enhance the cytotoxic effects of chemotherapeutic drugs. Furthermore, Reparixin can inhibit CXCR2 activation and may reduce neutrophil recruitment and vascular permeability during inflammation or injury.

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Drug Indications
Treatment of COVID-19
Treatment of COVID-19
Prevention of Transplant Rejection

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Chemical CXC ligand 8 (CXCL8)/IL-8 and its associated agonists recruit and activate polymorphonuclear cells by binding to CXC chemokine receptor 1 (CXCR1) and CXCR2. This article elucidates the unique mechanism of action of a small molecule inhibitor of CXCR1 and CXCR2 (repertaxin). Structural and biochemical data are consistent with a non-competitive allosteric interaction pattern between CXCR1 and repertaxin, which blocks signal transduction by locking CXCR1 in an inactive conformation. Repertaxin is a potent inhibitor of polymorphonuclear cell recruitment in vivo and protects organs from reperfusion injury. Targeting the repertaxin interaction site of CXCR1 is a general strategy for modulating chemokine receptor activity. [3]

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Background and Purpose: Acute lung injury (ALI) remains a major challenge in the field of intensive care medicine. Neutrophils and chemokines are considered key factors in the development of ALI. The main chemokine receptor on neutrophils is CXCR2, which regulates neutrophil recruitment and vascular permeability, but no small molecule CXCR2 inhibitor has been shown to be effective for ALI or ALI animal models. To study the functional relevance of the CXCR2 inhibitor Reparixin in vivo, we determined its role in two acute lung injury (ALI) models induced by lipopolysaccharide (LPS) inhalation or acid perfusion, respectively. Experimental methods: In two mouse ALI models, we used the Evans blue method to measure vascular permeability and used flow cytometry to assess the recruitment of neutrophils to pulmonary vessels, interstitium and alveoli. [2] Mechanism of action: Reparixin, as a non-competitive allosteric inhibitor of CXCR1 and CXCR2, blocks downstream signaling pathways (calcium mobilization, chemotaxis) without displacing CXCL8 from its receptor. This can prevent the recruitment and activation of neutrophils under inflammatory conditions [1,2,5]
- Therapeutic potential: Reparixin is being investigated for the treatment of inflammatory diseases, including ischemia-reperfusion injury, acute lung injury, and rheumatoid arthritis, due to its ability to reduce neutrophil-mediated tissue damage [5]

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Reparixin L-lysine salt is a potent, orally effective, non-competitive allosteric antagonist that antagonizes CXCR1 and CXCR2. It is developed in the form of lysine salt, which has improved water solubility and bioavailability compared to the free acid form [1][3]
- Its core mechanism of action is to bind to the transmembrane allosteric site of CXCR1/CXCR2, inducing conformational changes that block downstream signal transduction (calcium mobilization, ERK/PI3K activation) without competing with CXCL8 for binding sites. Orthogonal binding site [1][2][5] - Preclinical data support its potential therapeutic use in inflammatory diseases (myocardial ischemia-reperfusion injury), bone diseases (osteoporosis) and pain management. Its mechanism of action is through inhibition of CXCR1/CXCR2-mediated recruitment of inflammatory cells (neutrophils) and inhibition of pro-inflammatory/pro-bone resorption signaling [4][5] - Pharmacokinetic differences between species (longer half-life in dogs than in rats) and differences in target binding affinity (Ki value in rodents is higher than in humans) should be considered in clinical translation [3][2] - The compound has good drug-like characteristics, including good oral bioavailability, moderate tissue distribution, low toxicity and no significant risk of drug interactions, supporting its potential for long-term oral administration [3]

C₂₀H₃₅N₃O₅S

429.57

429.23

C, 53.97; H, 8.03; N, 8.58; O, 22.87; S, 6.55

266359-93-7

Reparixin; 266359-83-5

9932389

Off-white to light yellow solid powder

4.913

4

7

10

29

495

2

S(C([H])([H])[H])(N([H])C([C@]([H])(C([H])([H])[H])C1C([H])=C([H])C(=C([H])C=1[H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H])=O)(=O)=O.O([H])C([C@]([H])(C([H])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H])N([H])[H])=O

JEJFWWFZAQBZMJ-GVKMLHTLSA-N

InChI=1S/C14H21NO3S.C6H14N2O2/c1-10(2)9-12-5-7-13(8-6-12)11(3)14(16)15-19(4,17)18;7-4-2-1-3-5(8)6(9)10/h5-8,10-11H,9H2,1-4H3,(H,15,16);5H,1-4,7-8H2,(H,9,10)/t11-;5-/m10/s1

(2S)-2,6-diaminohexanoic acid;(2R)-2-[4-(2-methylpropyl)phenyl]-N-methylsulfonylpropanamide

2934.99.9001

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.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.82 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.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (5.82 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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (5.82 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.

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Solubility in Formulation 4: 40 mg/mL (93.12 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)