Mavorixafor (AMD-070; AMD11070, AMD070, X4P-001) is an orally bioavailable CXCR4 antagonist with an IC50 value of 13 nM in a CXCR4 125I-SDF inhibition binding assay, it inhibits the replication of T-tropic HIV-1 (NL4.3 strain) in MT-4 cells and PBMCs. The proliferation and progression of tumor cells are facilitated by the upregulation of the CXC chemokine receptor CXCR2 in a range of distinct tumor cell types. Reduced tumorigenesis and metastasis were the results of CXCR2 inhibition. SX-682 has the ability to treat cancer because it is a CXCR2 antagonist. AMD-070 has been assessed in phase I/II trials by X4 Pharmaceuticals in various solid tumor types. There may be a further application for this substance in the management of HIV-1 infection.

Physicochemical Properties

Molecular Formula	C₂₁H₂₇N₅
Molecular Weight	349.47
Exact Mass	349.226
Elemental Analysis	C, 72.17; H, 7.79; N, 20.04
CAS #	558447-26-0
Related CAS #	Mavorixafor trihydrochloride; 2309699-17-8
PubChem CID	11256587
Appearance	White to gray solid powder
Density	1.2±0.1 g/cm3
Boiling Point	597.0±50.0 °C at 760 mmHg
Melting Point	108-110ºC
Flash Point	314.9±30.1 °C
Vapour Pressure	0.0±1.7 mmHg at 25°C
Index of Refraction	1.656
LogP	2.78
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	7
Heavy Atom Count	26
Complexity	431
Defined Atom Stereocenter Count	1
SMILES	NCCCCN(CC1=NC2=C(N1)C=CC=C2)[C@@H]3C4=C(CCC3)C=CC=N4
InChi Key	WVLHHLRVNDMIAR-IBGZPJMESA-N
InChi Code	InChI=1S/C21H27N5/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)/t19-/m0/s1
Chemical Name	N'-(1H-benzimidazol-2-ylmethyl)-N'-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine
Synonyms	AMD 11070; AMD-070; X4P-001; AMD-11070; AMD 070; X4P 001; X4P001; AMD11070; AMD070; mavorixafor
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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.
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 )
ln Vitro	In vitro activity: 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].
ln Vivo	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].
Enzyme Assay	The compounds are first preincubated in SUP-T1 T cells for 30 minutes on ice, with 1 serving as a control. Following this, the cells are washed with PBS containing 2% FCS and then incubated with PE-conjugated anti-CXCR4 mAb for an additional 30 minutes on ice. The cell samples are first fixed with 1% paraformaldehyde in PBS and then examined using an FACS Calibur flow cytometer after being cleaned in PBS. The average fluorescence intensity values are used to calculate the compounds' dose-dependent inhibitory effects on mAb binding.
Cell Assay	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].
Animal Protocol	Mice: In a pathogen-free environment, BALB/c nude mice are raised. As soon as the mice reach eight weeks of age, the experiments begin. In summary, 1×106 nude mice have their blood vessels inoculated with the cells. Day 49 is the time of the mice's sacrifice. H&E staining is used to determine whether distant metastases are present or absent. The mice are given 0.2 mL of saline as a vehicle or the same volume of Mavorixafor (AMD-070) (2 mg/kg) orally every day as part of their experimental chemotherapy treatment[2].
References	[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]. Impact of a CXCL12/CXCR4 Antagonist in Bleomycin (BLM) Induced Pulmonary Fibrosis and Carbon Tetrachloride (CCl4) Induced Hepatic Fibrosis in Mice. PLoS One. 2016 Mar 21;11(3):e0151765. [3]. Effect of a novel orally bioavailable CXCR4 inhibitor, AMD070, on the metastasis of oral cancer cells. Oncol Rep. 2018 Jul;40(1):303-308.
Additional Infomation	AMD 070 is an aminoquinoline. Mavorixafor is a small molecule drug candidate that belongs to a new investigational class of anti-HIV drugs known as entry (fusion) inhibitors. Currently there is only one FDA-approved entry inhibitor, enfuvirtide (Fuzeon), that is available for the treatment of HIV infection. Several experimental entry inhibitors are now in early stage testing, including mavorixafor. Mavorixafor is a selective allosteric antagonist of the CXCR4 receptor on HIV, preventing the virus from entering and infecting healthy cells. 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. Drug Indication Investigated for use/treatment in HIV infection. 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

Solubility Data

Solubility (In Vitro)	DMSO: ~70 mg/mL (~200.3 mM) Water: NA Ethanol: ~70 mg/mL
Solubility (In Vivo)	5%DMSO + 40%PEG300 + 5%Tween 80 + 50%ddH2O: 3.5mg/ml (10.02mM) (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.8615 mL	14.3074 mL	28.6148 mL
	5 mM	0.5723 mL	2.8615 mL	5.7230 mL
	10 mM	0.2861 mL	1.4307 mL	2.8615 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.