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Mavorixafor | CAS No: 558447-26-0 | GMP-certified suppliers
A medication that inhibits CXCR4 receptors to block viral entry, under investigation for treating HIV infection by targeting specific virus subtypes resistant to other therapies.
Therapeutic categories
Primary indications
- Investigated for use/treatment in HIV infection
Product Snapshot
- Mavorixafor is an oral small molecule formulation
- It is primarily investigated for therapeutic use in HIV infection
- The compound is currently in the investigational stage with no approved regulatory status
Clinical Overview
Mavorixafor is a selective allosteric antagonist of the C-X-C chemokine receptor type 4 (CXCR4), a coreceptor utilized by specific HIV strains to enter and infect CD4+ immune cells. By binding CXCR4, mavorixafor inhibits the interaction between the receptor and the HIV envelope glycoprotein gp120, thereby blocking viral entry and subsequent replication. Approximately 5% of HIV strains are purely CXCR4-tropic, while around 35% can use both CXCR4 and CCR5, making CXCR4 inhibition a targeted approach for these subpopulations. CXCR4-using virus is associated with accelerated CD4 cell decline and disease progression.
Pharmacodynamically, mavorixafor has demonstrated potent inhibition of CXCR4-dependent viral strains, including those resistant to other antiretroviral classes. It shows additive or synergistic activity when combined in vitro with standard HIV therapies. Preclinical data indicate oral bioavailability, favorable pharmacokinetics, and acceptable toxicity profiles supporting oral dosing.
Metabolic and excretory parameters typical of this compound class suggest a suitable drug-like profile, although comprehensive ADME data remain limited due to its investigational status. Safety considerations focus on the selective targeting of CXCR4 to minimize off-target effects on other chemokine receptors, with preliminary studies indicating specificity and tolerability.
Mavorixafor is currently in clinical investigation and has not received regulatory approval. Enfuvirtide (Fuzeon) remains the sole entry inhibitor approved to date.
From an API sourcing and quality standpoint, mavorixafor’s classification as an aminoquinoline derivative implies the need for stringent control of synthetic intermediates and impurity profiles. Suppliers should ensure compliance with Good Manufacturing Practices (GMP) and provide detailed certificates of analysis addressing purity, residual solvents, and stereochemical integrity to meet regulatory expectations.
Identification & chemistry
| Generic name | Mavorixafor |
|---|---|
| Molecule type | Small molecule |
| CAS | 558447-26-0 |
| UNII | 0G9LGB5O2W |
| DrugBank ID | DB05501 |
Pharmacology
| Summary | AMD-070 is a small molecule HIV entry inhibitor that selectively targets the CXCR4 chemokine receptor on host immune cells, blocking viral binding and preventing infection by CXCR4-using HIV strains. By inhibiting the interaction between the viral envelope glycoprotein and CXCR4, AMD-070 disrupts viral entry and fusion processes critical for HIV replication. This mechanism addresses strains resistant to existing therapies by preventing the virus from entering healthy cells. |
|---|---|
| Mechanism of action | Chemokine receptors expressed on the surface of immune cells are known to play a critical role in virus infection and transmission. CXCR4, and another chemokine receptor CCR5, are involved in HIV infection. The process of HIV entry begins with binding of the viral envelope glycoprotein to both the CD4 receptor and one of only two chemokine receptors, and ends with fusion of viral and cell membranes. Viral entry provides novel therapeutic targets against HIV. To date, at least 3 sub classes of HIV viral entry/fusion inhibitors have emerged: 1. CD4 binding or attachment - targets initial recognition and binding of the viral glycoprotein gp120 to the cell-surface CD4 antigen. 2. Chemokine co-receptor binding - targets binding of virus to the CCR5 or CXCR4 co-receptor. 3. Fusion Inhibition - targets the viral glycoprotein gp41 inhibiting the fusion of virus with the cell. Different strains of HIV prefer one receptor or the other, or may use either receptor to infect cells. * 35% of strains use both CXCR4 and CCR5 * 5% of strains are pure CXCR4 using * 60% of strains are pure CCR5 using * An infected individual may harbor different levels of both CXCR4 and CCR5 using virus * CXCR4 using virus independently predicts CD4 decline and HIV clinical progression and is associated with earlier mortality |
| Pharmacodynamics | AMD-070 is a small molecule drug candidate that belongs to a new investigational class of anti-HIV drugs known as entry (fusion) inhibitors. Approximately 76% of HIV-patients with measurable viral load are infected with a strain of virus that is resistant to one or more classes of antiretroviral agents, thus reducing treatment options. Unlike many existing HIV drugs that target the virus after it has infected a healthy cell, AMD-070 blocks the virus from entering a healthy cell, thus preventing the replication process. AMD-070 targets the CXCR4 receptor on HIV and prevents the virus from entering and infecting healthy cells. * AMD-070 is specific for the CXCR4 receptor and does not interact with any other chemokine receptors in vitro * AMD-070 strongly inhibits viral infection by all CXCR4 using virus (including virus using CXCR4 alone and/or virus using CXCR4 and CCR5) in vitro * AMD-070 is orally bioavailable in animals * Suitable PK and toxicity profile for oral dosing * AMD-070 shows additive or synergistic effects in vitro in combination with other known anti-HIV agents * AMD-070 is active against CXCR4 using HIV strains that are resistant to existing antiretroviral therapies in vitro * Potent anti-HIV activity against CXCR4-using laboratory strains and clinical isolates |
Targets
| Target | Organism | Actions |
|---|---|---|
| C-X-C chemokine receptor type 4 | Humans | antagonist, inhibitor |
| C-C chemokine receptor type 5 | Humans |
Formulation & handling
- Mavorixafor is a small molecule compound suitable for oral administration given its physicochemical properties. Limited water solubility suggests formulation strategies may require solubilizers or alternative delivery technologies. Stability considerations should include protection from moisture due to its solid state and low aqueous solubility.
Regulatory status
Mavorixafor is a type of Additives
Additives in the pharmaceutical API category refer to a group of chemical substances that are incorporated into pharmaceutical products to enhance their stability, functionality, or performance. These additives play a crucial role in ensuring the quality, safety, and efficacy of medications.
One common type of additive used in pharmaceuticals is preservatives. Preservatives are added to prevent microbial growth and maintain the integrity of the product throughout its shelf life. They help to safeguard against contamination and maintain the potency of the active pharmaceutical ingredient (API). Some commonly used preservatives include benzyl alcohol, phenol, and parabens.
Another important group of additives is antioxidants. Antioxidants are added to pharmaceutical formulations to prevent or delay the oxidation of APIs, which can lead to degradation and loss of potency. Examples of antioxidants commonly used in pharmaceuticals include ascorbic acid (vitamin C) and tocopherols (vitamin E).
In addition to preservatives and antioxidants, other additives like flavorings, colorants, and sweeteners may be incorporated into pharmaceutical products to improve their palatability and patient acceptability.
It is crucial to note that the use of additives in pharmaceuticals is strictly regulated by health authorities to ensure their safety and efficacy. Manufacturers must comply with stringent quality control standards and guidelines to guarantee the proper use and appropriate levels of additives in pharmaceutical products.
Overall, additives play a vital role in the pharmaceutical industry by enhancing the stability, functionality, and patient acceptability of medications. Their careful selection and incorporation contribute to the overall quality and effectiveness of pharmaceutical products.
