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Purity: ≥98%
| Targets |
CXCR4/CXCL12 ( IC50 ~10 nM )
MSX-122 selectively targets the CXCR4 receptor, a G protein-coupled receptor that plays a critical role in cell migration, invasion, and metastasis. It acts as a partial antagonist, blocking the CXCL12/CXCR4 signaling pathway. By inhibiting this pathway, MSX-122 reduces tumor cell migration, invasion, and metastasis. It has an IC₅₀ of 10 nM for inhibition of CXCR4/CXCL12 actions. |
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| ln Vitro |
MSX-122, which has an IC50 of approximately 10 nM, is a partial antagonist of CXCR4, blocking CXCR4/CXCL12 actions. When the corresponding ligands, CCR3/CCL5 and CCR5/CCL5, mediate the reduction of cAMP, MSX-122 exhibits no inhibition. Invasion of 78% MDA-MB-231 cells is potently blocked by MSX-122 (100 nM). But in the calcium flux assay, MSX-122 is inert and does not inhibit T-tropic HIV infection[1].
In vitro, MSX-122 is a potent inhibitor of CXCR4/CXCL12 actions with an IC₅₀ of 10 nM. It acts as a partial antagonist of the CXCR4 receptor. Its activity can be assessed using cell-based assays measuring CXCR4-mediated signaling, such as calcium mobilization or chemotaxis, in response to CXCL12 stimulation. |
| ln Vivo |
MSX-122 (10 mg/kg, i.p.) inhibits inflammation induced by carrageenan and lung fibrosis induced by bleomycin in mice. In an animal model of breast cancer metastasis used in experiments, MSX-122 (4 mg/kg, i.p., daily) prevents metastasis. Moreover, the number of hepatic micrometastases is significantly reduced by MSX-122 (10 mg/kg i.p., daily)[1].
In vivo, MSX-122 is orally bioavailable and has been used in trials studying the treatment of solid tumors. Its oral bioavailability and potent activity against CXCR4 make it a suitable candidate for in vivo studies of cancer and other diseases where CXCR4 signaling is implicated. |
| Enzyme Assay |
Non-cellular receptor binding assays for MSX-122 involve competitive radioligand binding displacement studies using membrane preparations from cells expressing the human CXCR4 receptor. Membranes are incubated with a radiolabeled CXCR4 ligand (e.g., [¹²⁵I]-CXCL12) and varying concentrations of MSX-122. Following incubation and filtration, bound radioactivity is measured, and IC₅₀ values are determined from displacement curves.
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| Cell Assay |
MSX-122 is preincubated at 1, 10, 100, and 1000 nM on MDA-MB-231 cells grown in an 8-well slide chamber for the binding affinity assay. Following an incubation period with 50 nM biotinylated TN14003 and a fixation step using 4% formaldehyde, the cells are then stained with rhodamine.
In vitro cellular assays for MSX-122 involve treating cells expressing CXCR4 with the compound and measuring receptor-mediated signaling and function. For signaling, cells are loaded with a calcium-sensitive dye and stimulated with CXCL12 in the presence of varying concentrations of MSX-122. The inhibition of calcium mobilization is quantified. For function, cell migration or invasion assays are performed using transwell chambers, where cells migrate towards a CXCL12 gradient in the presence of the compound. |
| Animal Protocol |
Mice: Female nude mice aged six to eight weeks are injected via the tail vein with 1.5×1066 MDA-MB-231 breast cancer cells mixed with the compound (1 µM, less than 5 min preincubation) (10/group). The mice in the treated group are injected intraperitoneally (i.p.) with 4 mg/kg MSX-122ms (salt form) every day starting the next day. Thirty-five days after the tumor cell injection, the animals are killed. Complete lung tissues are taken and sectioned for H&E histochemistry and real-time RT-PCR for human CXCR4 in order to assess the metastatic tumor area in five fields per section under a microscope. The results are confirmed by repeating these experiments. 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. In the mouse model for uveal melanoma micrometastasis, 1×106 wild-type OMM2.3 cells expressing HGF/TGF-β/CXCR4/MMP2 are injected into the posterior chamber of the right eye of each mouse on day 0. On day three, mice are given 10 mg/kg MSX-122 intraperitoneally (i.p.) in 0.1 mL of 45% CD volume per day, while the control group receives 0.1 mL of 45% CD injections only. Day 7: Tumor-bearing eyes are removed. Histological techniques are used to monitor tumor growth. The number of hepatic micrometastases is counted under a microscope on day 28, after hepatic tissues have been extracted, preserved in 10% formalin, processed, and stained with H&E. The average number of micrometastases per section is calculated by microscopically examining six sections through the liver's center for the presence of micrometastases (<100 µm diameter). For each group, ten mice are used. A table summarizing animal experiments for three metastasis models can be found in the Data S3[1].
In vivo animal experiments with MSX-122 are conducted in mouse xenograft models of solid tumors. Tumor-bearing mice are treated with MSX-122 via oral administration. Tumor growth, metastasis, and angiogenesis are assessed. The compound's ability to inhibit tumor cell migration, invasion, and metastasis is evaluated. |
| ADME/Pharmacokinetics |
MSX-122 has a molecular weight of 292.34 and a molecular formula of C₁₆H₁₆N₆. It is a solid powder with a purity of ≥98%. The compound is soluble in DMSO (10 mM). For storage, the powder should be kept at -20°C for up to 3 years or at 4°C for up to 2 years; stock solutions can be stored at -80°C for 6 months or at -20°C for 1 month.
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| Toxicity/Toxicokinetics |
MSX-122 is a research compound for laboratory use only and is not approved for human therapeutic use. In preclinical studies, it has been generally well-tolerated at therapeutic doses. As a CXCR4 antagonist, it may affect the immune system and hematopoiesis. Standard laboratory safety precautions should be followed when handling the compound.
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| References | |
| Additional Infomation |
MSX-122 is currently being used in clinical trials for the treatment of solid tumors. The CXCR4 inhibitor Q-122 is an orally bioavailable CXCR4 inhibitor with potential antitumor and antiviral activity. The CXCR4 inhibitor MSX-122 binds to the chemokine receptor CXCR4, preventing stromal cell-derived factor-1 (SDF-1) from binding to and activating the receptor, which may lead to reduced tumor cell proliferation and migration. CXCR4 is a chemokine receptor belonging to the GPCR (G protein-coupled receptor) gene family, playing an important role in chemotaxis and angiogenesis, and is upregulated in various tumor cell types; it is also a co-receptor for HIV entry into T cells.
MSX-122 (CAS 897657-95-3) is a novel, small-molecule, orally bioavailable partial antagonist of CXCR4. It has an IC₅₀ of 10 nM for inhibition of CXCR4/CXCL12 actions and has been used in trials for the treatment of solid tumors. MSX-122 is available from various commercial suppliers for research applications. |
| Molecular Formula |
C16H16N6
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|---|---|
| Molecular Weight |
292.338441848755
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| Exact Mass |
292.144
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| Elemental Analysis |
C, 65.74; H, 5.52; N, 28.75
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| CAS # |
897657-95-3
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| Related CAS # |
897657-95-3
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| PubChem CID |
11687907
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| Appearance |
White solid powder
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| LogP |
2.636
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
22
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| Complexity |
263
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1C(NCC2C=CC(CNC3N=CC=CN=3)=CC=2)=NC=CC=1
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| InChi Key |
PXZXYRKDDXKDTK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H16N6/c1-7-17-15(18-8-1)21-11-13-3-5-14(6-4-13)12-22-16-19-9-2-10-20-16/h1-10H,11-12H2,(H,17,18,21)(H,19,20,22)
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| Chemical Name |
N-[[4-[(pyrimidin-2-ylamino)methyl]phenyl]methyl]pyrimidin-2-amine
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| Synonyms |
MSX 122; MSX122; MSX-122
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: 3~4 mg/mL (10.3~13.7 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.4 mg/mL (1.37 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 4.0 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: ≥ 0.4 mg/mL (1.37 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 4.0 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. View More
Solubility in Formulation 3: ≥ 0.4 mg/mL (1.37 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 10 mg/mL (34.21 mM) in 0.5% CMC-Na/saline water (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4207 mL | 17.1034 mL | 34.2067 mL | |
| 5 mM | 0.6841 mL | 3.4207 mL | 6.8413 mL | |
| 10 mM | 0.3421 mL | 1.7103 mL | 3.4207 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT03518138 | Completed | Drug: Q-122 Drug: Placebo |
Vasomotor Symptoms (VMS) |
Que Oncology | October 24, 2018 | Phase 2 |
| NCT04080297 | Completed | Drug: oral capsule of Q-122 | Vasomotor Symptoms (VMS) |
Que Oncology | January 10, 2014 | Phase 1 |
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