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Mavorixafor HCl (also known as AMD-1107, AMD070, X4P-001) is a potent, selective and orally bioavailable antagonist of CXCR4 with anti-HIV activity. It inhibits CXCR4 with an IC50 value of 13 nM in a CXCR4 125I-SDF inhibition binding assay, also inhibits the replication of T-tropic HIV-1 (NL4.3 strain) in MT-4 cells and PBMCs. The CXC chemokine receptor CXCR2 is upregulated in a variety of different tumor cell types and involved in tumor cell proliferation and progression. Inhibition of CXCR2 led to reduced metastasis and decreased tumorigenesis. As a CXCR2 antagonist, SX-682 has the potential to treat cancer. AMD-070 has been evaluated in phase I/II studies in different solid tumors by X4 Pharmaceuticals. This compound also has the potential use for the treatment of HIV-1 infection.
On April 29, 2024, the U.S. Food and Drug Administration (FDA) approved mavorixafor (trademarked as Xolremdi by X4 Pharmaceuticals) for the treatment of warts, hypogammaglobulinemia, immunodeficiency, myelokathexis (WHIM) syndrome.Physicochemical Properties
| Molecular Formula | C21H28CLN5 | |
| Molecular Weight | 385.933523178101 | |
| Exact Mass | 385.203 | |
| CAS # | 880549-30-4 | |
| Related CAS # | 558447-26-0;880549-30-4 (HCl); 2309699-17-8 | |
| PubChem CID | 71576687 | |
| Appearance | Light yellow to brown solid at room temperature | |
| LogP | 5.078 | |
| Hydrogen Bond Donor Count | 3 | |
| Hydrogen Bond Acceptor Count | 4 | |
| Rotatable Bond Count | 7 | |
| Heavy Atom Count | 27 | |
| Complexity | 431 | |
| Defined Atom Stereocenter Count | 1 | |
| SMILES | N([C@H]1CCCC2C=CC=NC1=2)(CCCCN)CC1=NC2C=CC=CC=2N1.Cl |
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| InChi Key | DBNMEMJSDAAGNZ-FYZYNONXSA-N | |
| InChi Code | InChI=1S/C21H27N5.ClH/c22-12-3-4-14-26(15-20-24-17-9-1-2-10-18(17)25-20)19-11-5-7-16-8-6-13-23-21(16)19;/h1-2,6,8-10,13,19H,3-5,7,11-12,14-15,22H2,(H,24,25);1H/t19-;/m0./s1 | |
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| 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 |
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| 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
| Targets | 125I-SDF-CXCR4 ( IC50 = 13 nM ); HIV-1 (NL4.3 strain) ( IC50 = 1 nM ); HIV-1 (NL4.3 strain) ( IC50 = 9 nM ); HIV-1 (NL4.3 strain) ( IC50 = 3 nM ); HIV-1 (NL4.3 strain) ( IC50 = 26 nM ) | ||
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| ADME/Pharmacokinetics |
Absorption In adults with WHIM syndrome, the mean (CV%) Cmax at steady-state is 3304 (58.6%) ng/mL and the AUC from 0 to 24 hours (AUC0-24h) is 13970 (58.4%) ngxh/mL following 400 mg once daily. Mavorixafor demonstrates nonlinear pharmacokinetics with greater than dose-proportional increases in Cmax and AUC0-24h over a dose range of 50 mg (0.125 times the recommended dosage) to 400 mg. Mavorixafor steady-state is reached after approximately 9 to 12 days at the highest approved recommended dosage in healthy subjects. Mavorixafor median (range) Tmax is 2.8 hours (1.9 to 4 hours) at the highest approved recommended dosage. Food decreases Cmax and AUC. Route of Elimination After a single oral dose of radiolabeled mavorixafor, 74.2% of the administered dose was recovered out of which 61.0% of administered radioactivity was recovered in feces and 13.2% (3% unchanged) was recovered in the urine over the 240-hour collection period in healthy subjects. Volume of Distribution Mavorixafor volume of distribution was 768 L in adults with WHIM syndrome. Clearance The mean (CV%) apparent clearance was 62 L/h (40%) following a single-dose administration of mavorixafor 400 mg in healthy subjects. Mavorixafor exhibits at least partial nonlinear apparent clearance; however, this is not clinically significant at the approved recommended dosage. Protein Binding In vitro, mavorixafor is >93% bound to human plasma proteins. Metabolism / Metabolites Mavorixafor is metabolized by CYP3A4 and, to a lesser extent, CYP2D6. Biological Half-Life The mean (CV%) terminal half-life was 82 h (34%) following a single-dose administration of mavorixafor 400 mg in healthy subjects. Mavorixafor (AMD070) is an orally bioavailable small molecule; good oral bioavailability was observed in both rats and dogs [1] - In CD-1 mice, after oral administration of Mavorixafor (AMD070) at 400 μg/animal, the drug was detected in the lung tissue, and its concentration varied over time, with the EC₉₀ (44 ng/mL) used as a reference threshold for pharmacodynamic activity [2] - In C57BL/6 mice, following intraperitoneal administration of Mavorixafor (AMD070), the drug was distributed in plasma, liver, and lung tissues, with measurable concentrations at different time points [2] |
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| Toxicity/Toxicokinetics |
Mavorixafor (AMD070) was noncytotoxic to MT-4 cells and PBMCs at concentrations exceeding 23 μM in vitro [1] Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on the use of mavorixafor during breastfeeding. The manufacturer recommends not breastfeeding treatment and for three weeks after the final dose. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. |
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| References | PLoS One.2016 Mar 21;11(3):e0151765;J Med Chem.2010 Apr 22;53(8):3376-88. | ||
| Additional Infomation |
Mavorixafor is a CXC chemokine receptor 4 (CXCR4) antagonist. It was first approved by the FDA on April 30, 2024, for the treatment of warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome, a genetic immunodeficiency disorder characterized by a reduced number of mature neutrophils and lymphocytes. WHIM syndrome is caused by mutations in the CXCR4 gene, which leads to overactivation of CXCR4 signalling pathways. Mavorixafor prevents the activation of CXCR4. As CXCR4 mutations have also been implicated in human immunodeficiency virus (HIV), Waldenstrom’s macroglobulinemia (WM), B-cell non-Hodgkin lymphoma, and solid tumours, including melanoma, mavorixafor is being investigated in these conditions.
Mavorixafor is a CXC Chemokine Receptor 4 Antagonist. The mechanism of action of mavorixafor is as a CXC Chemokine Receptor 4 Antagonist, and Cytochrome P450 2D6 Inhibitor, and Cytochrome P450 3A4 Inhibitor, and P-Glycoprotein Inhibitor. Mavorixafor is an orally bioavailable inhibitor of C-X-C chemokine receptor type 4 (CXCR4), with potential antineoplastic and immune checkpoint inhibitory activities. Upon administration, mavorixafor selectively binds to CXCR4 and prevents the binding of CXCR4 to its ligand, stromal cell-derived factor 1 (SDF-1 or CXCL12). This inhibits receptor activation and results in decreased proliferation and migration of CXCR4-overexpressing tumor cells. In addition, inhibition of CXCR4 prevents the recruitment of regulatory T-cells and myeloid-derived suppressor cells (MDSCs) to the tumor microenvironment, thereby abrogating CXCR4-mediated immunosuppression and enabling the activation of a cytotoxic T-lymphocyte-mediated immune response against cancer cells. The G protein-coupled receptor CXCR4, which is upregulated in several tumor cell types, induces the recruitment of immunosuppressive cells in the tumor microenvironment, suppresses immune surveillance, and promotes tumor angiogenesis and tumor cell proliferation. It is also a co-receptor for HIV entry into T-cells. MAVORIXAFOR is a small molecule drug with a maximum clinical trial phase of IV (across all indications) that was first approved in 2024 and is indicated for neoplasm and has 6 investigational indications. a derivative of AMD3100; a CXCR4 blocker |
Solubility Data
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5911 mL | 12.9557 mL | 25.9114 mL | |
| 5 mM | 0.5182 mL | 2.5911 mL | 5.1823 mL | |
| 10 mM | 0.2591 mL | 1.2956 mL | 2.5911 mL |