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AMD 070

AMD 070 structure

CAS No:
558447-26-0
Formula:
C21H27N5
Chemical Name:
AMD 070
Synonyms:
AMD 070;N-(1H-benzimidazol-2-ylmethyl)-N-[(8S)-5,6,7,8-tetrahydro-8-quinolinyl]- (9CI);N'-(1H-Benzimidazol-2-ylmethyl)-N'-((S)-5,6,7,8-tetrahydroquinolin-8-yl)butane-1,4-diamine;AMD 070 N-(1H-benziMidazol-2-ylMethyl)-N-[(8S)-5,6,7,8-tetrahydro-8-quinolinyl]- (9CI);1,4-ButanediaMine, N-(1H-benziMidazol-2-ylMethyl)-N-[(8S)-5,6,7,8-tetrahydro-8-quinolinyl]-;(S)-N1-((1H-benzo[d]iMidazol-2-yl)Methyl)-N1-(5,6,7,8-tetrahydroquinolin-8-yl)butane-1,4-diaMine;AMD070/AMD-070;(S)-N1-((1H-Benzo[d]imidazol-2-yl)methyl)-N1-(5,6,7,8-tetrahydroquinolin-8-yl)butane-1,4-diami
Categories:
Organic Chemistry > Amides

Description

AMD-070 is a potent, selective and orally available CXCR4 antagonist, with an IC50 value of 13 nM against CXCR4 125I-SDF binding, and also 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.

AMD 070 is an aminoquinoline.|AMD-070 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 AMD-070, which targets the CXCR4 receptor on HIV and prevents the virus from entering and infecting healthy cells. Other entry inhibitors target the CCR5 receptor of HIV.These new agents are widely viewed as next generation anti-HIV drugs with the potential to significantly advance HIV therapeutics.|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.

AMD 070 Basic Attributes

Molecular Weight：

349.479

Exact Mass：

349.226654

UNII：

0G9LGB5O2W

NCI Thesaurus Code：

C126660

HScode：

2933990090

Characteristics

PSA：

70.8

XLogP3：

2.78

Density：

1.2±0.1 g/cm3

Melting Point：

108-110℃

Boiling Point：

597.0±50.0 °C at 760 mmHg

Flash Point：

314.9±30.1 °C

Refractive Index：

1.656

Drug Information

Drug Indication：

Investigated for use/treatment in HIV infection.

Pharmacology：

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

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

MeSH Entry Terms：

AMD 070

AMD 070 Use and Manufacturing

Use Classification：

Human drugs -> Rare disease (orphan)

Computed Properties

Molecular Weight:349.5
XLogP3:2.4
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:7
Exact Mass:349.22664588
Monoisotopic Mass:349.22664588
Topological Polar Surface Area:70.8
Heavy Atom Count:26
Complexity:431
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes