¹²⁵I-SDF-1-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 )

Mavorixafor (AMD-070) is an effective and readily available oral CXCR4 antagonist. It inhibits the replication of T-tropic HIV-1 (NL4.3 strain) in MT-4 cells and PBMCs with an IC50 of 1 and 9 nM, respectively, and has an IC50 value of 13 nM against CXCR4 ¹²⁵I-SDF binding. Regarding other chemokine receptors (CCR1, CCR2b, CCR4, CCR5, CXCR1, and CXCR2), mavorixafor (AMD-070) exhibits no effect[1]. The growth, migration, and matrigel invasion of B88-SDF-1 cells are significantly suppressed by mavorixafor (AMD-070) at 6.6 µM[2].

Mavorixafor (AMD-070) (2 mg/kg, p.o.) decreases the expression of human Alu DNA in mice and dramatically reduces the number of metastatic lung nodules in mice without causing a decrease in body weight[2].

On a 96-well plate, 5 × 10³ cells/well are seeded with DMEM containing 10% FCS. The cells are treated with or without 2 µM AMD3100 or 6.6 µM AMD-070 after a 24-hour period. An assay employing MTT is used to quantify the number of cells after 24 or 48 hours[2].

Absorption
In adults with WHIM syndrome, after a once-daily dose of 400 mg, the steady-state mean (CV%) Cmax was 3304 (58.6%) ng/mL, and the 0-24 hour AUC (AUC0-24h) was 13970 (58.4%) ng·h/mL. The pharmacokinetics of Mavorixafor are non-linear; the increases in Cmax and AUC0-24h are greater than dose-proportional across the dose range of 50 mg (0.125 times the recommended dose) to 400 mg. In healthy subjects, steady-state plasma concentrations of Mavorixafor are reached approximately after 9 to 12 days following administration of the highest approved recommended dose. At the highest approved recommended dose, the median (range) Tmax of Mavorixafor is 2.8 hours (1.9 to 4 hours). Food decreases Cmax and AUC.
Excretion Route
In healthy subjects, following a single oral dose of radiolabeled mavolixafor, 74.2% of the administered dose was recovered within a 240-hour collection period, with 61.0% of the radioactive material recovered in feces and 13.2% (3% unchanged) in urine.
Volume of Distribution
In adults with WHIM syndrome, the volume of distribution of mavolixafor is 768 L.
Clearance
In healthy subjects, following a single dose of 400 mg mavolixafor, the mean (coefficient of variation) apparent clearance was 62 L/h (40%). Mavolixafor exhibits at least partially nonlinear apparent clearance; however, this nonlinear clearance is not clinically significant at the approved recommended dose.
Protein Binding
In vitro studies have shown that mavolixafor binds to human plasma proteins >93%.
Metabolism/Metabolites
Mavolixafor is primarily metabolized via CYP3A4, and secondarily via CYP2D6.
Biological Half-Life
In healthy subjects, the mean (CV%) terminal half-life after a single dose of 400 mg mavolixafor is 82 hours (34%).
Mavorixafor (AMD070) is a small molecule drug with high oral bioavailability; good oral bioavailability was observed in both rats and dogs [1]
- In CD-1 mice, after oral administration of 400 μg/mouse of Mavorixafor (AMD070), the drug was detected in lung tissue, and its concentration varied over time. EC₉₀ (44 ng/mL) was used as the reference threshold for pharmacodynamic activity [2]
- In C57BL/6 mice, after intraperitoneal injection of Mavorixafor (AMD070), the drug was distributed in plasma, liver, and lung tissue, and its concentration was detected at different time points [2]

Use during pregnancy and lactation
◉ Summary of use during lactation
There is currently no information regarding the use of mavolixafor during lactation. The manufacturer recommends against breastfeeding during treatment and for three weeks after the last dose.
◉ Effects on breastfed infants
As of the revision date, no published information was found.
◉ Effects on lactation and breast milk
As of the revision date, no published information was found.

[1]. Discovery of novel small molecule orally bioavailable C-X-C chemokine receptor 4 antagonists that are potent inhibitors of T-tropic (X4) HIV-1 replication. J Med Chem. 2010 Apr 22;53(8):3376-88.

[2]. Effect of a novel orally bioavailable CXCR4 inhibitor, AMD070, on the metastasis of oral cancer cells. Oncol Rep. 2018 Jul;40(1):303-308.

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, infection, and bone marrow retention (WHIM) syndrome. WHIM syndrome is a inherited immunodeficiency disorder characterized by a decrease in the number of mature neutrophils and lymphocytes. WHIM syndrome is caused by mutations in the CXCR4 gene, leading to overactivation of the CXCR4 signaling pathway. Mavorixafor inhibits CXCR4 activation. Because CXCR4 mutations are also associated with human immunodeficiency virus (HIV), Waldenström macroglobulinemia (WM), B-cell non-Hodgkin lymphoma, and solid tumors including melanoma, Mavorixafor is being investigated in these diseases. Mavorixafor's mechanism of action is as a CXC chemokine receptor 4 antagonist, cytochrome P450 2D6 inhibitor, cytochrome P450 3A4 inhibitor, and P-glycoprotein inhibitor. Mavorixafor is an orally bioavailable CXC chemokine receptor 4 (CXCR4) inhibitor with potential antitumor and immune checkpoint inhibitory activities. After administration, Mavorixafor selectively binds to CXCR4, preventing CXCR4 from binding to its ligand stromal cell-derived factor 1 (SDF-1 or CXCL12). This inhibits receptor activation, leading to reduced proliferation and migration of CXCR4-overexpressing tumor cells. Furthermore, inhibition of CXCR4 prevents the recruitment of regulatory T cells and myeloid-derived suppressor cells (MDSCs) to the tumor microenvironment, thereby eliminating CXCR4-mediated immunosuppression and activating cytotoxic T lymphocyte-mediated immune responses against cancer cells. The G protein-coupled receptor CXCR4 is upregulated in various tumor cell types, inducing the recruitment of immunosuppressive cells to the tumor microenvironment, inhibiting immune surveillance, and promoting tumor angiogenesis and tumor cell proliferation. It is also a co-receptor for HIV entry into T cells. Mavorixafor is a small molecule drug, currently in Phase IV clinical trials (covering all indications), and was first approved in 2024 for the treatment of cancer, with six investigational indications. It is a derivative of AMD3100, a CXCR4 blocker.

C21H30CL3N5

458.855401515961

457.16

C, 54.97; H, 6.59; Cl, 23.18; N, 15.26

2309699-17-8

Mavorixafor; 558447-26-0; 880549-30-4

78357868

Light yellow to yellow solid powder

5

4

7

29

431

1

Cl.Cl.Cl.N(CC1=NC2C=CC=CC=2N1)(CCCCN)[C@@H]1C2C(=CC=CN=2)CCC1

FTHQTOSCZZCGHB-VLEZWVESSA-N

InChI=1S/C21H27N5.3ClH/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);3*1H/t19-;;;/m0.../s1

N'-(1H-benzimidazol-2-ylmethyl)-N'-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine;trihydrochloride

Mavorixafor triHCl; Mavorixafor trihydrochloride; 2309699-17-8; Mavorixafor (trihydrochloride); AMD-070 trihydrochloride; C21H30Cl3N5; AMD-070 trihydrochloride

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)

DMSO: ~150 mg/mL (~326.9 mM)
H2O: ~100 mg/mL (~217.9 mM)

Solubility in Formulation 1: ≥ 2.62 mg/mL (5.71 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
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: ≥ 2.62 mg/mL (5.71 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
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: ≥ 0.6 mg/mL (1.31 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 6.0 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 4: ≥ 0.6 mg/mL (1.31 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 6.0 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 5: ≥ 0.6 mg/mL (1.31 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 6.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 6: 100 mg/mL (217.93 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.)