Xolremdi (mavorixafor)
Research Synopsis
- - Recent research on Xolremdi (mavorixafor) highlights its role as a selective CXCR4 antagonist, crucial for targeting HIV-1 entry into host cells.
- - Studies show that mavorixafor demonstrates a strong efficacy against CXCR4-tropic HIV-1 strains, indicating its potential for expanding treatment options for HIV patients.
- - Clinical evaluations of mavorixafor have reported favorable pharmacokinetic profiles, revealing effective absorption and distribution in the body which supports its oral bioavailability.
- - Safety assessments indicate that mavorixafor has a good tolerability profile with mild side effects, including headaches and gastrointestinal discomfort observed in trials.
- - Research also suggests that mavorixafor can enhance the effectiveness of combination therapies, particularly in cases of drug-resistant cancers, by inhibiting the CXCR4-CXCL12 signaling pathway.
- - The drug's potential is emphasized in studies showing it can reduce the invasiveness of gemcitabine-resistant pancreatic cancer cells, showcasing its applicability beyond HIV treatment.
- - Molecular dynamics simulations and docking studies provide insights into the binding interactions of mavorixafor, aiding in the design of more effective CXCR4 inhibitors.
- - Preliminary findings suggest that the allosteric modulation mechanism of mavorixafor alters receptor function rather than outright blocking, paving the way for innovative therapeutic strategies.
- - Overall, mavorixafor's multifaceted actions against HIV-1 and its potential in oncology present it as a promising drug candidate in the ongoing search for advanced HIV therapeutics and cancer treatments.
Xolremdi (mavorixafor)
A novel transmembrane CXCR4 variant that expands the WHIM genotype-phenotype paradigm.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
HIV co-receptor drugs on the horizon.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Multiple-dose escalation study of the safety, pharmacokinetics, and biologic activity of oral AMD070, a selective CXCR4 receptor inhibitor, in human subjects.
London, UK
2 hours ago
1 Received
- AMD070 is an oral medication that blocks the CXCR4 receptor and shows promise against a specific strain of HIV, tested on healthy male volunteers with varying dosages.
- The drug was generally well tolerated, with mild side effects like headaches and gastrointestinal issues, and demonstrated a dose-dependent increase in white blood cell count, indicating its activity in the body.
- Food intake significantly reduced the drug's effectiveness; however, the pharmacokinetics suggested that it was still active at the highest doses tested, reaching effective levels against HIV.
$100 - $150
Hourly Rate
Pharmacokinetic effect of AMD070, an Oral CXCR4 antagonist, on CYP3A4 and CYP2D6 substrates midazolam and dextromethorphan in healthy volunteers.
London, UK
2 hours ago
1 Received
- Many antiretroviral drugs used for HIV treatment are impacted by the metabolism of CYP3A4 and CYP2D6 enzymes, which can lead to drug interactions, complicating patient care.
- A study with 12 healthy individuals assessed how AMD070, a new HIV entry inhibitor, affects the metabolism of midazolam and dextromethorphan when taken together.
- Results showed significant increases in the levels of dextromethorphan and midazolam when combined with AMD070, indicating potential drug interactions that need further investigation for their clinical relevance in HIV treatment.
$100 - $150
Hourly Rate
Effect of low-dose ritonavir on the pharmacokinetics of the CXCR4 antagonist AMD070 in healthy volunteers.
London, UK
2 hours ago
1 Received
- AMD070, a drug that fights HIV by blocking CXCR4, was tested to see how it's affected by ritonavir, which can influence drug metabolism.
- In a study with 23 male participants, AMD070 was given alone and then with ritonavir, revealing increased blood concentrations of AMD070 when combined with ritonavir.
- Results showed that after 14 days of ritonavir treatment, the levels of AMD070 in the bloodstream were significantly higher, suggesting that ritonavir enhances the effects of AMD070 in the body.
$100 - $150
Hourly Rate
Comparison of the potential multiple binding modes of bicyclam, monocylam, and noncyclam small-molecule CXC chemokine receptor 4 inhibitors.
London, UK
2 hours ago
1 Received
- CXCR4 is a key receptor involved in various biological processes and acts as a coreceptor for HIV, making it a potential target for new antiretroviral drugs.
- This study investigates the binding interactions of three different small-molecule inhibitors with CXCR4, particularly focusing on a specific nonmacrocyclic inhibitor, AMD11070.
- The findings reveal how specific mutations in the receptor affect inhibitor binding, suggesting that there is a larger binding pocket than previously thought, which could guide the design of more effective and safer CXCR4 inhibitors in the future.
$100 - $150
Hourly Rate
Proof of activity with AMD11070, an orally bioavailable inhibitor of CXCR4-tropic HIV type 1.
London, UK
2 hours ago
1 Received
- The X4 Antagonist Concept Trial evaluated the safety and effectiveness of AMD11070, an oral drug targeting X4-tropic HIV, in patients with high levels of HIV in their blood.
- Patients took AMD11070 for 10 days, and results showed that 4 out of 9 evaluable individuals experienced a decrease in X4 virus levels, with some showing a shift to a less aggressive form of the virus.
- Overall, AMD11070 was well tolerated without significant safety issues, but its use is currently on hold due to liver changes seen in long-term animal studies, pending further safety evaluations.
$100 - $150
Hourly Rate
Amine substituted N-(1H-benzimidazol-2ylmethyl)-5,6,7,8-tetrahydro-8-quinolinamines as CXCR4 antagonists with potent activity against HIV-1.
London, UK
2 hours ago
1 Received
- Researchers synthesized new amine-substituted compounds based on N-(1H-benzimidazol-2-ylmethyl)-5,6,7,8-tetrahydro-8-quinolinamines that show strong effectiveness against HIV-1.
- The synthesis methods used allowed for different variations in the chemical structure, which affected how well the compounds worked against the virus.
- This work resulted in the discovery of compounds with exceptional anti-HIV-1 activity, demonstrating effectiveness at low and sub-nanomolar concentrations.
$100 - $150
Hourly Rate
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.
London, UK
2 hours ago
1 Received
- - The study created new oral drugs that effectively block the CXCR4 chemokine receptor, which HIV-1 uses to enter cells, enhancing potential treatments for HIV-1 infections.
- - A specific compound, AMD070, was identified as a strong CXCR4 antagonist with low toxicity and effective in inhibiting T-tropic HIV-1 replication in lab tests.
- - The drug showed good absorption when given orally in tests on rats and dogs, marking it as the first small molecule CXCR4 antagonist suitable for treating HIV-1.
$100 - $150
Hourly Rate
HIV-1 tropism.
London, UK
2 hours ago
1 Received
$100 - $150
Hourly Rate
Ligand-guided optimization of CXCR4 homology models for virtual screening using a multiple chemotype approach.
London, UK
2 hours ago
1 Received
- - CXCR4 is a receptor involved in various critical biological processes, including HIV infection, cancer progression, immune cell movement, and WHIM syndrome, making it a significant target for drug development.
- - Without an X-ray crystal structure for CXCR4, researchers used theoretical modeling and experimental data to create better ligand-receptor models that help identify how small molecules bind and act as antagonists.
- - The study improved the binding pocket of CXCR4 to better differentiate between effective antagonists and random compounds, leading to enhanced methods for structure-based drug design and finding new CXCR4 antagonists.
$100 - $150
Hourly Rate
Synthesis and SAR of novel CXCR4 antagonists that are potent inhibitors of T tropic (X4) HIV-1 replication.
London, UK
2 hours ago
1 Received
- Researchers optimized an early lead from the AMD070 program to create new compounds with heterocyclic structures.
- They developed a structure-activity relationship to identify potent antagonists that target CXCR4, which are crucial for HIV-1 treatment.
- The new compounds demonstrated effective anti-HIV-1 activity, inhibited calcium ion (Ca²+) flux, and showed favorable pharmacokinetics in both rats and dogs.
$100 - $150
Hourly Rate
Design of novel CXCR4 antagonists that are potent inhibitors of T-tropic (X4) HIV-1 replication.
London, UK
2 hours ago
1 Received
- * These new compounds demonstrated strong effectiveness against HIV-1.
- * They also exhibited excellent pharmacokinetic properties in tests with rats and dogs, indicating good absorption and distribution in the body.
$100 - $150
Hourly Rate
Combination of drug therapy in acute lymphoblastic leukemia with a CXCR4 antagonist.
London, UK
2 hours ago
1 Received
- The bone marrow stromal niche can shield acute lymphoblastic leukemia (ALL) cells from chemotherapy, contributing to relapse risks.
- Researchers explored AMD11070, a drug that blocks the CXCR4 receptor, to see if it could enhance the effectiveness of ALL treatments.
- Tests showed that combining AMD11070 with traditional chemotherapy drugs improved survival in mice with ALL, indicating it might help eliminate leukemia cells that hide in the bone marrow stroma.
$100 - $150
Hourly Rate
The molecular pharmacology of AMD11070: an orally bioavailable CXCR4 HIV entry inhibitor.
London, UK
2 hours ago
1 Received
- To infect human cells, HIV binds to the CD4 receptor and either CXCR4 or CCR5; AMD11070 is the first oral small molecule that targets CXCR4 in this context.
- AMD11070 effectively inhibits various interactions related to CXCR4, including SDF-1α binding and SDF-1 induced cellular responses, showing its potency through several assays with low IC50 values.
- The compound is selective for CXCR4, meaning it does not affect other receptors like CXCR3 or CCR5, and operates as an allosteric inhibitor, suggesting it alters receptor function rather than blocking it outright.
$100 - $150
Hourly Rate
Inhibition of CXCR4-CXCL12 chemotaxis in melanoma by AMD11070.
London, UK
2 hours ago
1 Received
- There is currently no cure for metastatic melanoma, and CXCR4 is a key receptor that influences its spread to organs like the liver, but existing treatment options for blocking this receptor are limited.
- Researchers tested a new drug, AMD11070, against CXCR4 to see how well it could prevent melanoma cell movement compared to AMD3100, a previously known antagonist.
- The results showed that AMD11070 was much more effective at stopping melanoma cell migration, regardless of the presence of the B-RAF-V600E mutation, suggesting it could be a promising new treatment for different types of melanoma.
$100 - $150
Hourly Rate
Anti-HIV small-molecule binding in the peptide subpocket of the CXCR4:CVX15 crystal structure.
London, UK
2 hours ago
1 Received
- CXCR4 is a chemokine receptor that plays a role in cell movement and allows HIV-1 to enter cells, making it an important target for drug development.
- Recent research highlighted structural differences in CXCR4 when bound to different compounds, specifically the small molecule IT1t and the peptide CVX15, showing variability in how these molecules interact with the receptor.
- The study found that the binding of the antagonist AMD11070 to the CVX15 model is more consistent with experimental data, suggesting that this receptor structure may offer a better site for drug binding than the IT1t structure does.
$100 - $150
Hourly Rate
Hologram quantitative structure activity relationship, docking, and molecular dynamics studies of inhibitors for CXCR4.
London, UK
2 hours ago
1 Received
- * The study explores the activity of AMD11070 and its derivatives using techniques like HQSAR, docking, and molecular dynamics simulations, revealing AMD11070's strong antiretroviral effects.
- * Key amino acids Asp97 and Glu288 influence binding interactions, and the presence of a butyl amine group in AMD11070 is crucial for its effectiveness, providing insights for future drug development targeting CXCR4.
$100 - $150
Hourly Rate
Studying the binding interactions of allosteric agonists and antagonists of the CXCR4 receptor.
London, UK
2 hours ago
1 Received
- Recent studies have highlighted various allosteric modulators of GPCRs, particularly focusing on the CXCR4 receptor and how these compounds affect its activity.
- Pepducins like ATI-2341 serve as agonists through allosteric mechanisms, while small organic molecules such as AMD11070 and GSK812397 act as antagonists; however, the incomplete understanding of where these ligands bind complicates insights into their function.
- The research utilizes advanced modeling techniques, including blind docking and molecular dynamics, to propose two distinct binding sites for these modulators and identifies key binding residues for their interactions with the CXCR4 receptor.
$100 - $150
Hourly Rate
Enhancement of the CXCL12/CXCR4 axis due to acquisition of gemcitabine resistance in pancreatic cancer: effect of CXCR4 antagonists.
London, UK
2 hours ago
1 Received
- The study focuses on the CXCL12-CXCR4 signaling pathway, which is crucial for tumor growth and metastasis, particularly in pancreatic cancer (PaCa) that is resistant to the chemotherapy drug gemcitabine (GEM).
- Researchers created two GEM-resistant PaCa cell lines and assessed the expression of CXCR4 in these cells and CXCL12 in surrounding fibroblasts, discovering that CXCR4 levels were significantly higher in GEM-resistant cells.
- The use of CXCR4 antagonists was effective in reducing both the invasiveness and tumor formation of GEM-resistant PaCa cells, highlighting their potential as a treatment strategy to combat resistance to chemotherapy.
$100 - $150
Hourly Rate