CXCR2 antagonist 7 (compound 19) is a potent CXCR2 antagonist. CXCR2 antagonist 7 shows potent CXCR2 binding affinity (IC50=0.044 µM) and calcium mobilization (IC50=0.66 µM)[ 1].
IC50 & Target
CXCR2
0.044 μM (IC50)
分子量
352.36
Formula
C14H14F2N6OS
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Van Hoof M, et al. Identification of novel chemotypes as CXCR2 antagonists via a scaffold hopping approach from a thiazolo[4,5-d]pyrimidine. Eur J Med Chem. 2022; 235:114268.
CXCR2 antagonist 7 (compound 19) is a potent CXCR2 antagonist. CXCR2 antagonist 7 shows potent CXCR2 binding affinity (IC50=0.044 µM) and calcium mobilization (IC50=0.66 µM)[ 1].
IC50 & Target
CXCR2
0.044 μM (IC50)
分子量
352.36
Formula
C14H14F2N6OS
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Van Hoof M, et al. Identification of novel chemotypes as CXCR2 antagonists via a scaffold hopping approach from a thiazolo[4,5-d]pyrimidine. Eur J Med Chem. 2022; 235:114268.
CXCR2 antagonist 7 (compound 19) is a potent CXCR2 antagonist. CXCR2 antagonist 7 shows potent CXCR2 binding affinity (IC50=0.044 µM) and calcium mobilization (IC50=0.66 µM)[ 1].
IC50 & Target
CXCR2
0.044 μM (IC50)
分子量
352.36
Formula
C14H14F2N6OS
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Van Hoof M, et al. Identification of novel chemotypes as CXCR2 antagonists via a scaffold hopping approach from a thiazolo[4,5-d]pyrimidine. Eur J Med Chem. 2022; 235:114268.
CXCR2 antagonist 6 (compound 35c) is a potent CXCR2 antagonist. CXCR2 antagonist 6 shows potent CXCR2 binding affinity (IC50=0.044 µM) and calcium mobilization (IC50=0.66 µM)[ 1].
IC50 & Target
CXCR2
0.43 μM (IC50)
分子量
362.40
Formula
C17H16F2N4OS
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Van Hoof M, et al. Identification of novel chemotypes as CXCR2 antagonists via a scaffold hopping approach from a thiazolo[4,5-d]pyrimidine. Eur J Med Chem. 2022; 235:114268.
CXCR2 antagonist 5 (compound 25) is a potent CXCR2 antagonist. CXCR2 antagonist 5 shows potent CXCR2 binding affinity (IC50=0.013 µM) and calcium mobilization (IC50=0.1 µM)[ 1].
IC50 & Target
CXCR2
0.013 μM (IC50)
分子量
352.36
Formula
C15H14F2N4O2S
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Van Hoof M, et al. Identification of novel chemotypes as CXCR2 antagonists via a scaffold hopping approach from a thiazolo[4,5-d]pyrimidine. Eur J Med Chem. 2022; 235:114268.
CXCR2 antagonist 6 (compound 35c) is a potent CXCR2 antagonist. CXCR2 antagonist 6 shows potent CXCR2 binding affinity (IC50=0.044 µM) and calcium mobilization (IC50=0.66 µM)[ 1].
IC50 & Target
CXCR2
0.43 μM (IC50)
分子量
362.40
Formula
C17H16F2N4OS
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Van Hoof M, et al. Identification of novel chemotypes as CXCR2 antagonists via a scaffold hopping approach from a thiazolo[4,5-d]pyrimidine. Eur J Med Chem. 2022; 235:114268.
CXCR2 antagonist 6 (compound 35c) is a potent CXCR2 antagonist. CXCR2 antagonist 6 shows potent CXCR2 binding affinity (IC50=0.044 µM) and calcium mobilization (IC50=0.66 µM)[ 1].
IC50 & Target
CXCR2
0.43 μM (IC50)
分子量
362.40
Formula
C17H16F2N4OS
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Van Hoof M, et al. Identification of novel chemotypes as CXCR2 antagonists via a scaffold hopping approach from a thiazolo[4,5-d]pyrimidine. Eur J Med Chem. 2022; 235:114268.
CXCR2 antagonist 5 (compound 25) is a potent CXCR2 antagonist. CXCR2 antagonist 5 shows potent CXCR2 binding affinity (IC50=0.013 µM) and calcium mobilization (IC50=0.1 µM)[ 1].
IC50 & Target
CXCR2
0.013 μM (IC50)
分子量
352.36
Formula
C15H14F2N4O2S
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Van Hoof M, et al. Identification of novel chemotypes as CXCR2 antagonists via a scaffold hopping approach from a thiazolo[4,5-d]pyrimidine. Eur J Med Chem. 2022; 235:114268.
CXCR2 antagonist 5 (compound 25) is a potent CXCR2 antagonist. CXCR2 antagonist 5 shows potent CXCR2 binding affinity (IC50=0.013 µM) and calcium mobilization (IC50=0.1 µM)[ 1].
IC50 & Target
CXCR2
0.013 μM (IC50)
分子量
352.36
Formula
C15H14F2N4O2S
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Van Hoof M, et al. Identification of novel chemotypes as CXCR2 antagonists via a scaffold hopping approach from a thiazolo[4,5-d]pyrimidine. Eur J Med Chem. 2022; 235:114268.
IT1t dihydrochloride is a potent CXCR4 antagonist; inhibits CXCL12/CXCR4 interaction with an IC50 of 2.1 nM.
IC50 & Target
CXCL12/CXCR4
2.1 nM (IC50)
HIV-1 (X4)
14.2 nM (IC50, in MT-4 cells)
HIV-1 (X4)
19 nM (IC50, in PBMCs)
体外研究 (In Vitro)
The CXCR4 is involved in chemotaxis and serves as a coreceptor for T-tropic HIV-1 viral entry and in cancer metastasis. IT1t is a small, drug-like, isothiourea derivative. IT1t shows very potent and dose-dependent inhibition of the CXCL12/CXCR4 interaction with an IC50 of 2.1 nM. This calcium flux is also inhibited by IT1t with an IC50 of 23.1[1]. Strong electron density is observed for IT1t in the binding cavity of both subunits of the CXCR4 homodimer. In dimers of CXCR4 bound to IT1t, the monomers interact only at the extracellular side of helices V and VI, leaving at least a 4 Å gap between the intracellular regions, which is presumably filled by lipids. The IT1t compound and CVX15 peptide have both been characterized as competitive inhibitors of CXCL12, and many of the receptor-ligand contacts in the co-crystal structures presented are important for CXCL12 binding, including the acidic Asp187, Glu2887.39 and Asp972.63. The binding site of IT1t may point to the major anchor region for this domain[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
IT1t reduces the formation of TNBC early metastases in the zebrafish xenograft model. Tumor cell invasion at the metastatic site is effectively reduced upon CXCR4 silencing (Fig. 7B), similar to the antagonist IT1t [3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
479.57
Formula
C21H36Cl2N4S2
CAS 号
1092776-63-0
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Van Hout A, et al. Comparison of cell-based assays for the identification and evaluation of competitive CXCR4 inhibitors. PLoS One. 2017 Apr 14;12(4):e0176057.
[2]. Wu B, et al. Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science. 2010 Nov 19;330(6007):1066-71.
[3]. Tulotta C, et al. Inhibition of signaling between human CXCR4 and zebrafish ligands by the small molecule IT1timpairs the formation of triple-negative breast cancer early metastases in a zebrafish xenograft model. Dis Model Mech. 2016 Feb;9(2):141-53.
Cell Assay [1]
Jurkat cells are incubated with serial dilutions (0.001, 0.01, 0.1, 1, 10, 100, 1000 μM) of IT1t at room temperature for two hours. Cytotoxicity of IT1t is also evaluated at 37°C over a longer period of time in MT-4 cells and PHA-stimulated PBMCs (ten day incubation) because these cell types are used in anti-HIV activity assays which last up to ten days. Cytotoxicity is evaluated microscopically and viability is assessed using the a kit[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Van Hout A, et al. Comparison of cell-based assays for the identification and evaluation of competitive CXCR4 inhibitors. PLoS One. 2017 Apr 14;12(4):e0176057.
[2]. Wu B, et al. Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science. 2010 Nov 19;330(6007):1066-71.
[3]. Tulotta C, et al. Inhibition of signaling between human CXCR4 and zebrafish ligands by the small molecule IT1timpairs the formation of triple-negative breast cancer early metastases in a zebrafish xenograft model. Dis Model Mech. 2016 Feb;9(2):141-53.
SB225002, a potent, selective and non-peptide CXCR2 antagonist, inhibits 125I-IL-8 binding to CXCR2 with an IC50 of 22 nM.
IC50 & Target[1]
125I-IL-8-CXCR2
22 nM (IC50, in CHO cell membrane)
体外研究 (In Vitro)
SB225002 (SB 225002) is an antagonist of 125I-IL-8 binding to CXCR2 with an IC50=22 nM. SB225002 shows >150-fold selectivity over CXCR1 and four other 7-TMRs tested. SB225002 is a potent antagonist of rabbit CXCR2, inhibiting rabbit PMN chemotaxis in response to optimal concentrations of human IL-8 or GROα (IC50 values of 30 and 70 nM, respectively. In these cells (PMN, HL60, CXCR1-RBL-2H3), SB225002 produces a concentration-dependent inhibition of both IL-8- and GROα-mediated calcium mobilization with IC50 values of 8 and 10 nM, respectively. In 3ASubE cells stably transfected with CXCR2, SB 225002 dose-dependently inhibits calcium mobilization induced by both GROα and IL-8, with IC50 values of 20 and 40 nM, respectively[1]. WHCO1 cells treated with SB225002 exhibits a 40% reduction in cell proliferation. Blocking CXCR2 signaling in WHCO1 cells with 400 nM SB225002 (SB 225002) significantly decreases cell proliferation by ~40% to 50%[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
SB225002 (SB 225002) selectively blocks IL-8-induced neutrophil margination in rabbits[1]. CXCR2 is blocked using the selective antagonist SB225002 (2 mg/kg) or neutralizing CXCR2 antiserum. The CXCR2 antagonist SB225002 decreases neutrophil counts in ischemic hemispheres of ApoE−/− mice on Western diet and wildtype mice on normal diet[3]. SB225002 significantly attenuates microglial activation and BBB damage, increases myelination, and reduces astrogliosis in the white matter after LPS-sensitized HI[4].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
352.14
Formula
C13H10BrN3O4
CAS 号
182498-32-4
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. White JR, et al. Identification of a potent, selective non-peptide CXCR2 antagonist that inhibits interleukin-8-induced neutrophil migration. J Biol Chem. 1998 Apr 24;273(17):10095-8.
[2]. Wang B, et al. A growth-related oncogene/CXC chemokine receptor 2 autocrine loop contributes to cellular proliferation in esophageal cancer. Cancer Res. 2006 Mar 15;66(6):3071-7.
[3]. Herz J, et al. Role of Neutrophils in Exacerbation of Brain Injury After Focal Cerebral Ischemia in Hyperlipidemic Mice. Stroke. 2015 Oct;46(10):2916-25.
[4]. Wang LY, et al. CXCL5 signaling is a shared pathway of neuroinflammation and blood-brain barrier injury contributing to white matter injury in the immature brain. J Neuroinflammation. 2016 Jan 6;13:6.
[5]. Shi ZR, et al. Decrease of galectin-3 in keratinocytes: A potential diagnostic marker and a critical contributor to the pathogenesis of psoriasis. J Autoimmun. 2018 May;89:30-40.
Kinase Assay [1]
CHO-CXCR1 and CHO-CXCR2 membranes are prepared. Assays are performed in 96-well microtiter plates where the reaction mixture contained 1.0 μg/mL membrane protein in 20 mM Bis-Tris-propane, pH 8.0, with 1.2 mM MgSO4, 0.1 mM EDTA, 25 mM NaCl, and 0.03% CHAPS and SB 225002 (10 mM stock in Me2SO) added at the indicated concentrations, the final Me2SO concentration is <1% under standard binding conditions. Binding is initiated by addition of 0.25 nM 125I-IL-8 (2,200 Ci/mmol). After 1-h incubation at room temperature the plate is harvested using a Tomtec 96-well harvester onto a glass fiber filtermat blocked with 1% polyethyleneimine, 0.5% BSA and washed three times with 25 mM NaCl, 10 mM Tris•HCl, 1 mM MgSO4, 0.5 mMEDTA, 0.03% CHAPS, pH 7.4. The filter is dried, sealed in a sample bag containing 10 mL of Wallac 205 Betaplate liquid scintillation fluid, and counted with a Wallac 1205 Betaplate liquid scintillation counter[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Cell Assay [2]
Three esophageal squamous cell carcinoma cell lines WHCO1, WHCO5, and WHCO6 originally established from surgical biopsies of primary esophageal squamous cell carcinomas are cultured in DMEM containing 10% FCS at 37°C in a humidified atmosphere of 5% CO2. MTT assays are carried out using the Cell Proliferation kit. Briefly, 1.5×103 cells are plated in 96-well plates in a final volume of 180 μL DMEM per well. SB 225002 (400 nM) is added to cells and 0.001% DMSO (solvent) is added as a control. After the indicated incubation period, 18 μL of the MTT labeling reagent (final concentration 0.5 mg/mL) is added to each well and incubated for 4 hours in a humidified atmosphere. One hundred eighty microliters of the solubilization solution are added to each well and the plates are left overnight at 37°C. The spectrophotometric absorbance of samples is measured at 595 nm using a microtiter plate reader[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [3][4]
Mice[3] Male 7-8 weeks old wildtype (C57BL/6J, Harlan) and ApoE−/− mice, which are generated on the same C57BL/6 background, are either fed with a normal chow or a cholesterol rich chow for 6 weeks and submitted to 20 min of left-sided middle cerebral artery occlusion (MCAO) or sham surgery. Animals are randomly attributed to treatment paradigms, and experimenters are blinded at all stages of interventions and data analysis. The selective CXCR2 antagonist SB225002 (2 mg/kg) or vehicle (1% DMSO in PBS) is injected intraperitoneally (i.p.) at 0, 24 and 48 hours post-ischemia. In other experiments, CXCR2 is specifically blocked by i.p. injection of a neutralizing rabbit anti-CXCR2 serum (300 μL) at 0 hours, 24 hours and 48 hours post-ischemia. In the latter studies, normal rabbit serum (NRS) served as control. In some experiments, neutrophils are depleted by i.p. injection of 200 μg anti-mouse Ly6G 24 hours before and 24 hours after ischemia. In these experiments, 200 μg of an isotype control antibody is delivered as control. Rats[4] In this study, 10-12 Sprague-Dawley rat pups per dam are used. The pups receive intraperitoneal injections of SB225002 (1 or 3 mg/kg, diluted in NS containing 0.33 % Tween 80) or vehicle (NS solution containing 0.33 % Tween 80) 30 min before lipopolysaccharide (LPS) administration and immediately after hypoxic ischemia (HI). The pups are randomly assigned to four groups: control (pups unexposed to LPS or HI, N=14), vehicle (NS injections 30 min before LPS administration and immediately after HI, N=18), and SB-1 (1 mg/kg, N=14) and SB-3 (3 mg/kg, N=18) (SB225002 injections 30 min before LPS administration and immediately after HI).
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. White JR, et al. Identification of a potent, selective non-peptide CXCR2 antagonist that inhibits interleukin-8-induced neutrophil migration. J Biol Chem. 1998 Apr 24;273(17):10095-8.
[2]. Wang B, et al. A growth-related oncogene/CXC chemokine receptor 2 autocrine loop contributes to cellular proliferation in esophageal cancer. Cancer Res. 2006 Mar 15;66(6):3071-7.
[3]. Herz J, et al. Role of Neutrophils in Exacerbation of Brain Injury After Focal Cerebral Ischemia in Hyperlipidemic Mice. Stroke. 2015 Oct;46(10):2916-25.
[4]. Wang LY, et al. CXCL5 signaling is a shared pathway of neuroinflammation and blood-brain barrier injury contributing to white matter injury in the immature brain. J Neuroinflammation. 2016 Jan 6;13:6.
[5]. Shi ZR, et al. Decrease of galectin-3 in keratinocytes: A potential diagnostic marker and a critical contributor to the pathogenesis of psoriasis. J Autoimmun. 2018 May;89:30-40.
AMG 487 is an orally active and selective antagonist of CXC chemokine receptor 3 (CXCR3) which inhibits the binding of CXCL10 and CXCL11 to CXCR3 with IC50s of 8.0 and 8.2 nM, respectively[1].
IC50 & Target[1]
125I-IP10-CXCR3
8 nM (IC50)
125I-ITAC-CXCR3
8.2 nM (IC50)
体外研究 (In Vitro)
AMG 487 inhibits CXCR3-mediated cell migration by the three CXCR3 chemokines (IP-10 IC50=8 nM, ITAC IC50=15 nM, and MIG IC50=36 nM). Furthermore, AMG 487 inhibits calcium mobilization in response to ITAC (IC50=5 nM)[1]. AMG487 (1 μM) develops into fewer lung metastases, and the lungs are significantly smaller than vehicle-treated lungs[2]. AMG487 abrogates proliferation/survival of C26 tumour cells[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
AMG 487 (0.03-10 mg/kg, s.c.) exhibits significant reduction in cellular infiltration into the lungs in a dose dependent manner[1]. AMG487 (5 mg/kg, s.c., twice daily) develops fewer metastases than that in vehicle-treated mice[2]. AMG487 (5 mg/kg, s.c.)-treated mice exhibits fewer pulmonary nodules than the control mice in both the models. AMG487 reduces the tumour volume[3].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
603.59
Formula
C32H28F3N5O4
CAS 号
473719-41-4
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Johnson M, et al. Discovery and optimization of a series of quinazolinone-derived antagonists of CXCR3. Bioorg Med Chem Lett. 2007 Jun 15;17(12):3339-43.
[2]. Walser TC, et al. Antagonism of CXCR3 inhibits lung metastasis in a murine model of metastatic breast cancer. Cancer Res. 2006 Aug 1;66(15):7701-7.
[3]. Cambien B, et al. Organ-specific inhibition of metastatic colon carcinoma by CXCR3 antagonism. Br J Cancer. 2009 Jun 2;100(11):1755-64.
Cell Assay [3]
Colon cancer cells are seeded at a density of 104 cells cm2 and incubated either in serum-enriched medium or in base medium (containing 0.1% bovine serum albumin, BSA) supplemented or not with various concentrations of rCXCL9, rCXCL10 and rCXCL11 for the indicated periods of time before being either trypsin-detached, collected and enumerated or re-fed with fresh medium for 3 days, harvested and enumerated. The morphology of the CRC cells is observed through an inverted optical microscope at ×20 magnification, and photographs are taken at day 7.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [2]
Local tumor growth and spontaneous metastasis are evaluated by injecting 3×105 viable tumor cells s.c. proximal to the right abdominal mammary gland of syngeneic female mice. Tumor diameters are measured by caliper twice weekly, and mice are euthanized on an individual basis when the s.c. tumor measured 18 mm in diameter or earlier if the mouse seemed moribund. The lungs are removed and weighed, and surface tumor colonies are quantified in a blinded fashion under a dissecting microscope. Experimental metastasis is evaluated by injecting 9×104 viable tumor cells i.v. into the lateral tail vein of syngeneic female mice. All mice are euthanized on day 21 posttransplantation or earlier if the mice seemed moribund. The lungs are removed and weighed, and surface tumor colonies are quantified in a blinded fashion under a dissecting microscope. A 50% hydroxypropyl-β-cyclodextrin solution is prepared; at 20%, this solution serves as the vehicle. AMG487 is added to the 50% solution, and it is incubated in a sonicating water bath for 2 hours with occasional vortexing. Distilled water is added to give the appropriate final concentration of AMG487 in 20% of hydroxypropyl-β-cyclodextrin.
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Johnson M, et al. Discovery and optimization of a series of quinazolinone-derived antagonists of CXCR3. Bioorg Med Chem Lett. 2007 Jun 15;17(12):3339-43.
[2]. Walser TC, et al. Antagonism of CXCR3 inhibits lung metastasis in a murine model of metastatic breast cancer. Cancer Res. 2006 Aug 1;66(15):7701-7.
[3]. Cambien B, et al. Organ-specific inhibition of metastatic colon carcinoma by CXCR3 antagonism. Br J Cancer. 2009 Jun 2;100(11):1755-64.
LY2510924 is a potent and selective CXCR4 antagonist that blocks SDF-1 binding to CXCR4 with an IC50 of 0.079 nM.
IC50 & Target[1]
125I-SDF-1α-CXCR4
79.7 pM (IC50)
125I-SDF-1α-CXCR4
49.5 pM (Ki)
体外研究 (In Vitro)
LY2510924 specifically blocks SDF-1 binding to CXCR4 with IC50 value of 0.079 nM, and inhibits SDF-1–induced GTP binding with Kb value of 0.38 nM. In human lymphoma U937 cells expressing endogenous CXCR4, LY2510924 inhibits SDF-1–induced cell migration with IC50 value of 0.26 nM and inhibits SDF-1/CXCR4-mediated intracellular signaling. LY2510924 exhibits a concentration-dependent inhibition of SDF-1–stimulated phospho-ERK and phospho-Akt in tumor cells. Biochemical and cellular analyses reveals that LY2510924 has no apparent agonist activity[1]. LY2510924 chiefly inhibits the proliferation of AML cells with little induction of cell death and reduces protection against chemotherapy by stromal cells[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
LY2510924 specifically blocks SDF-1 binding to CXCR4 with IC50 value of 0.079 nM, and inhibits SDF-1–induced GTP binding with Kb value of 0.38 nM. In human lymphoma U937 cells expressing endogenous CXCR4, LY2510924 inhibits SDF-1–induced cell migration with IC50 value of 0.26 nM and inhibits SDF-1/CXCR4-mediated intracellular signaling. LY2510924 exhibits a concentration-dependent inhibition of SDF-1–stimulated phospho-ERK and phospho-Akt in tumor cells. Biochemical and cellular analyses reveals that LY2510924 has no apparent agonist activity[1]. LY2510924 chiefly inhibits the proliferation of AML cells with little induction of cell death and reduces protection against chemotherapy by stromal cells[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
1189.45
Formula
C62H88N14O10
CAS 号
1088715-84-7
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Peng SB, et al. Identification of LY2510924, a novel cyclic peptide CXCR4 antagonist that exhibits antitumor activities in solid tumor and breast cancer metastatic models. Mol Cancer Ther. 2015 Feb;14(2):480-90.
[2]. Cho BS, et al. Antileukemia activity of the novel peptidic CXCR4 antagonist LY2510924 as monotherapy and in combination with chemotherapy. Blood. 2015 Jul 9;126(2):222-32.
Kinase Assay
LY2510924 specifically blocks SDF-1 binding to CXCR4 with IC50 value of 0.079 nM, and inhibits SDF-1–induced GTP binding with Kb value of 0.38 nM. In human lymphoma U937 cells expressing endogenous CXCR4, LY2510924 inhibits SDF-1–induced cell migration with IC50 value of 0.26 nM and inhibits SDF-1/CXCR4-mediated intracellular signaling. LY2510924 exhibits a concentration-dependent inhibition of SDF-1–stimulated phospho-ERK and phospho-Akt in tumor cells. Biochemical and cellular analyses reveals that LY2510924 has no apparent agonist activity[1]. LY2510924 chiefly inhibits the proliferation of AML cells with little induction of cell death and reduces protection against chemotherapy by stromal cells[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [1]
Mice: SCID female mice are injected intravenously with MDA-MB-231 cells, and are treated subcutaneously with vehicle (1×PBS) or 3 mg/kg of LY2510924 formulated in 1×PBS. Group 1 and 2 animals receive vehicle or 3 mg/kg of LY2510924 twice daily for days with treatment beginning on one day before tumor cell injection. Group 3 animals receive 3 mg/kg of LY2510924 15 twice daily for 13 days with treatment beginning one day after tumor cell injection. After treatment, lung tissues are fixed in 10% neutral-buffered formalin for at least 24 hours and lung lobes are present in histologic sections[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Peng SB, et al. Identification of LY2510924, a novel cyclic peptide CXCR4 antagonist that exhibits antitumor activities in solid tumor and breast cancer metastatic models. Mol Cancer Ther. 2015 Feb;14(2):480-90.
[2]. Cho BS, et al. Antileukemia activity of the novel peptidic CXCR4 antagonist LY2510924 as monotherapy and in combination with chemotherapy. Blood. 2015 Jul 9;126(2):222-32.
WZ811 is an orally active, highly potent competitive antagonist of CXCR4. WZ811 efficiently inhibits CXCR4/SDF-1 (or CXCL12)-mediated modulation of cAMP levels (EC50=1.2 nM) and SDF-1 induced Matrigel invasion in cells (EC50=5.2 nM)[1].
IC50 & Target[1]
CXCR4
0.3 nM (EC50)
体外研究 (In Vitro)
WZ811 (Compound 32) is a potent CXCR4 antagonist, effectively inhibits TN14003 binding to CXCR4, with an EC50 of 0.3 nM[1]. WZ811 blocks SDF-1 mediated modulation cAMP levels in U87 glioma cells (EC50=1.2 nM) and Matirgel infiltration of MDA-MB-231 cells (EC50=5.2 nM)[1]. WZ811 (1-40 μM) inhibits TF-1 and UT-7 cells proliferation in a dose dependent manner both after treatment for 24 h and 48 h. Moreover, WZ811 (5 μM) induces cell apoptosis and enhances the sensitivity of cells to docetaxel. In addition, WZ811 inhibits aggressiveness markers and induces apoptosis in chronic lymphocytic leukemia cells[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
WZ811 (40 mg/kg, p.o.) blocks the lymphocytic leukemia cells growth on mouse xenograft models, and inhibits CXCR4/PI3K/AKT signaling pathway in mouse xenograft model of lymphocytic leukemia[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
分子量
290.36
Formula
C18H18N4
CAS 号
55778-02-4
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. WZ811, et al. Discovery of small molecule CXCR4 antagonists. J Med Chem. 2007 Nov 15;50(23):5655-64.
[2]. Li SH, et al. Suppression of chronic lymphocytic leukemia progression by CXCR4 inhibitor WZ811. Am J Transl Res. 2016 Sep 15;8(9):3812-3821.
Cell Assay [2]
In brief, cells are treated with WZ811 at 37°C for 24 h. After collection and washing with phosphate-buffered saline (PBS) buffer, cells are resuspended with staining buffer at a final density of 1 × 106/mL. Then, 5 μL annexin V-APC is added to 100 μL cell suspensions and incubated at room temperature in the dark for 10 min. Finally, cells are analyzed with FACS Calibur to determine cell apoptosis profiles[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration [2]
Mice[2] A total of 1 × 106 TF-1 cells in 100 μL of PBS are injected subcutaneously into dorsal flanks of an immunodeficient nude mouse. The animals are treated with WZ811 (40 mg/kg), or WZ811 once daily by oral gavage once the tumors have reached 100 mm3. Tumor growth and body weight is measured every three days during the treatment. The tumor volume (TV) is calculated every 3 days according to the following standard formula: TV (mm3) = length × width2 × 0.5[2].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. WZ811, et al. Discovery of small molecule CXCR4 antagonists. J Med Chem. 2007 Nov 15;50(23):5655-64.
[2]. Li SH, et al. Suppression of chronic lymphocytic leukemia progression by CXCR4 inhibitor WZ811. Am J Transl Res. 2016 Sep 15;8(9):3812-3821.
HF51116 is a potent antagonist of CXCR4. HF51116 strongly antagonizes SDF-1α-induced cell migration, calcium mobilization, and CXCR4 internalization. HF51116 inhibits HIV-1 infection via CXCR4. HF51116 has the potential for the research of HIV-1 infection, hematopoietic stem cell mobilization, and cancer metastasis[1].
分子量
522.73
Formula
C29H46N8O
CAS 号
2177311-29-2
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Fang X, et al. A fragment integrational approach to GPCR inhibition: Identification of a high affinity small molecule CXCR4 antagonist. Eur J Med Chem. 2022;231:114150.
MSX-122 is an orally active partial antagonist of CXCR4, inhibiting CXCR4/CXCL12 actions, with an IC50 of ∼10 nM. MSX-122 has anti-inflammatory and anti-metastatic activity.
IC50 & Target[1]
CXCR4/CXCL12
~10 nM (IC50)
体外研究 (In Vitro)
MSX-122 is a partial antagonist of CXCR4, inhibiting CXCR4/CXCL12 actions, with an IC50 of ∼10 nM. MSX-122 shows no inhibition on cAMP reduction mediated by their corresponding ligands CCR3/CCL5 and CCR5/CCL5. MSX-122 (100 nM) potently blocks invasion of 78% MDA-MB-231 cells. However, MSX-122 does not suppress T-tropic HIV infection and is inactive in calcium flux assay[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究 (In Vivo)
MSX-122 (10 mg/kg, i.p.) blocks inflammation induced by carrageenan and lung fibrosis induced by bleomycin in mice. MSX-122 (4 mg/kg, i.p., daily) blocks metastasis in an experimental animal model of breast cancer metastasis. Furthermore, MSX-122 (10 mg/kg i.p., daily) significantly decreases the numbers of hepatic micrometastases[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
分子量
292.34
Formula
C16H16N6
CAS 号
897657-95-3
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Liang Z, et al. Development of a unique small molecule modulator of CXCR4. PLoS One. 2012;7(4):e34038.
Animal Administration [1]
Mice[1] Six- to eight-week-old female nude mice are given injections of 1.5×106 MDA-MB-231 breast cancer cells mixed with the compound (1 µM, less than 5 min preincubation) through the tail vein (10/group). From the following day, mice in the treated group are given 4 mg/kg MSX-122ms (salt form) daily by i.p. injection. The animals are sacrificed 35 days after the tumor cell injection. Whole lung tissues are harvested and sectioned for real-time RT-PCR for human CXCR4 and H&E histostaining to evaluate the metastatic tumor area in five fields per section microscopically. These experiments are repeated once more to confirm the results. For the head and neck cancer animal model, metastatic subclones of 686LN-Ms cells are injected in the same way as MDA-MB-231 cells. [18F]FDG-PET is performed. For the uveal melanoma micrometastasis mouse model, on day 0, each mouse is inoculated with 1×106 wild-type OMM2.3 cells expressing HGF/TGF-β/CXCR4/MMP2 into the posterior chamber of right eye. On day 3, mice are treated with 10 mg/kg MSX-122 in 0.1 mL volume of 45% CD daily by i.p. injection, whereas the control mice are injected with 0.1 mL 45% CD only. On day 7, eyes with tumor are enucleated. The growth of tumor is checked by histological methods. On day 28, hepatic tissues are collected and fixed in 10% formalin, processed, H&E stained, and the number of hepatic micrometastases is counted under microscope. Six sections through the center of the liver are microscopically examined for the presence of micrometastases (<100 µm diameter) and the average number of micrometastases per section is determined. ten mice group are used. a table summarizing animal experiments for three metastasis models can be found in data s3[1].
上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献
[1]. Liang Z, et al. Development of a unique small molecule modulator of CXCR4. PLoS One. 2012;7(4):e34038.
VUF11207 fumarate (Compound 29) is a CXCR7 agonist and a high-potency CXCR7 (pKi of 8.1) ligand that induces recruitment of β-arrestin2 (pEC50 of 8.8) and subsequent internalization (pEC50 of 7.9) of CXCR7[1].
IC50 & Target[1]
CXCR7
8.1 (pKi)
分子量
586.65
Formula
C31H39FN2O8
CAS 号
1785665-61-3
运输条件
Room temperature in continental US; may vary elsewhere.
[1]. Wijtmans M, et al. Synthesis, modeling and functional activity of substituted styrene-amides as small-molecule CXCR7 agonists. Eur J Med Chem. 2012 May;51:184-92.
USL311 is a selective CXCR4 antagonist, with anti-tumor activity. USL311 prevents the binding of stromal-cell derived factor-1 (SDF-1 or CXCL12) to CXCR4[1].
IC50 & Target[1]
CXCR4
Clinical Trial
分子量
422.57
Formula
C24H34N6O
CAS 号
1373268-67-7
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
6 months
-20°C
1 month
溶解性数据
In Vitro:
DMSO : 18.57 mg/mL (43.95 mM; ultrasonic and warming and heat to 80°C)
CXCR7 antagonist-1 is an inhibitor of the binding of the SDF-1 chemokine (CXCL12 chemokine) or I-TAC (CXCL11) to the chemokine receptor CXCR. CXCR7 antagonist-1 prevents tumor cell proliferation, tumor formation, inflammatory diseases, and many other diseases (extracted from patent WO2014085490A1, compound 1.128)[1].
IC50 & Target
CXCR7
分子量
390.41
Formula
C21H19FN6O
CAS 号
1613021-99-0
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Junfa Fan, et al. Cxcr7 antagonists. Patent WO2014085490A1.
(±)-AMG 487 is a racemate of AMG 487. AMG 487 is an orally active and selective antagonist of CXC chemokine receptor 3 (CXCR3) which inhibits the binding of CXCL10 and CXCL11 to CXCR3 with IC50s of 8.0 and 8.2 nM, respectively[1].
分子量
603.59
Formula
C32H28F3N5O4
CAS 号
947536-03-0
运输条件
Room temperature in continental US; may vary elsewhere.
储存方式
Please store the product under the recommended conditions in the Certificate of Analysis.
参考文献
[1]. Johnson M, et al. Discovery and optimization of a series of quinazolinone-derived antagonists of CXCR3. Bioorg Med Chem Lett. 2007 Jun 15;17(12):3339-43.
