AMD-070

Names

[ Name ]:
AMD-070

[Synonym ]:
1,4-Butanediamine, N-(1H-benzimidazol-2-ylmethyl)-N-[(8S)-5,6,7,8-tetrahydro-8-quinolinyl]-
N'-(1H-benzimidazol-2-ylmethyl)-N'-[(8S)-5,6,7,8-tetrahydroquinolin-8-yl]butane-1,4-diamine
N-(1H-Benzimidazol-2-ylmethyl)-N-[(8S)-5,6,7,8-tetrahydro-8-quinolinyl]-1,4-butanediamine
AMD-070

Biological Activity

[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.

[Related Catalog]:

Signaling Pathways >> Anti-infection >> HIV

Research Areas >> Infection

[Target]

125I-SDF-CXCR4:13 nM (IC50)

HIV-1 (NL4.3 strain):1 nM (IC50, in MT-4 cells)

HIV-1 (NL4.3 strain):9 nM (IC50, in PBMCs)

HIV-1 (NL4.3 strain):3 nM (IC90, in MT-4 cells)

HIV-1 (NL4.3 strain):26 nM (IC90, in PBMCs)

[In Vitro]

AMD-070 is a potent 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 shows no effect on other chemokine receptors (CCR1, CCR2b, CCR4, CCR5, CXCR1, and CXCR2)[1]. AMD-070 (6.6 µM) significantly suppresses the anchorage-dependent growth, the migration and matrigel invasion of the B88-SDF-1 cells[2].

[In Vivo]

AMD-070 (2 mg/kg, p.o.) significantly reduces the number of metastatic lung nodules in mice, and lowers the expression of human Alu DNA in mice, without body weight loss[2].

[Cell Assay]

Cells are seeded on a 96-well plate at 5 × 103 cells/well in DMEM containing 10% FCS. Twenty-four hours later, the cells are treated with or without 2 µM AMD3100 or 6.6 µM AMD-070. After 24 or 48 h, the number of cells is quantified by an assay using MTT[2].

[Animal admin]

Mice[2] BALB/c nude mice are maintained under pathogen-free conditions. The experiments are initiated when the mice are 8 weeks of age. Briefly, the cells are inoculated into the blood vessels of nude mice (1× 106). These mice are sacrificed at day 49. The presence or absence of distant metastases is confirmed by hematoxylin and eosin (H&E) staining. For experimental chemotherapy, the mice are treated by the daily oral administration of 0.2 mL of saline for a vehicle or the same volume of AMD-070 (2 mg/kg)[2].

[References]

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

[3]. Chow LN, et al. 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.

[Related Small Molecules]

Reparixin | AMG 487 | SCH 527123 | Cenicriviroc | SB 225002 | AZD-5069 | LY2510924 | Ebselen | Triciribine | Raltegravir (potassium salt) | Tipranavir | DELAVIRDINE MESYLATE | Bictegravir | SCH 546738 | TAK-779

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
597.0±50.0 °C at 760 mmHg

[ Melting Point ]:
108-110ºC

[ Molecular Formula ]:
C₂₁H₂₇N₅

[ Molecular Weight ]:
349.473

[ Flash Point ]:
314.9±30.1 °C

[ Exact Mass ]:
349.226654

[ PSA ]:
70.83000

[ LogP ]:
2.78

[ Vapour Pressure ]:
0.0±1.7 mmHg at 25°C

[ Index of Refraction ]:
1.656

Safety Information

[ HS Code ]:
2933990090

Customs

[ HS Code ]: 2933990090

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%