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AMD-070  Audio icon

Other Names: AMD-11070
Drug Class: Entry and Fusion Inhibitors
Molecular Formula: C21 H27 N5
Registry Number: 558447-26-0 (CAS)
Chemical Name: N'-(1H-benzimidazol-2-ylmethyl)-N'-(5,6,7,8-tetrahydroquinolin-8-yl)butane-1,4-diamine
Chemical Class: Benzimidazoles
Company: Genzyme Corporation
Phase of Development: II
Chemical Image:
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Molecular Weight: 349.4793
(Compound details obtained from ChemIDplus Advanced1 and NIAID Therapeutics Database2)
Patent Version Content


Mechanism of Action: HIV-1 entry inhibitor. AMD-070 is a selective, reversible, small molecule CXCR4 chemokine coreceptor antagonist.3,4 AMD-070 prevents CXCR4-mediated viral entry of T-cell tropic synctium-inducing HIV (associated with advanced stages of HIV-1 infection) by binding to transmembrane regions of the coreceptor, blocking the interaction of the CD4–gp120 complex with the ECL2 domain of the CXCR4 coreceptor.3,4,5

: In healthy participants, the median estimated terminal half-life ranged from 7.6 to 12.6 hours (single-dose cohorts, 50 to 400 mg) and from 11.2 to 15.9 hours (multiple-dose cohorts, 100 to 400 mg twice daily).6

Metabolism/Elimination: AMD-070 is primarily eliminated by metabolism, with less than 1% of the administered oral dose appearing unchanged in the urine. In vitro studies using human liver microsomes have demonstrated that AMD-070 is metabolized by cytochrome P450 (CYP) 3A4 and to a lesser extent, CYP2D6. AMD-070 is a substrate of P-glycoprotein (P-gp).3

Resistance: In a 10-day monotherapy study (XACT) of twice daily AMD-070 100 mg or 200 mg in 10 HIV-infected adults, 9 participants had dual/mixed-tropic virus and 1 had X4-tropic virus at screening (determined by Trofile assay). One participant was determined to be non-evaluable. Of 4 responders achieving a reduction in X4 virus population of greater than or equal to 1 log10 relative luminescence units (rlu), 3 participants demonstrated a shift from dual/mixed virus to R5 virus. The shift to R5 tropism reverted back to dual/mixed tropism following completion of treatment by Day 30. Of the nonresponders, all but 1 participant maintained tropism during the study period, with the latter participant showing a shift from X4 tropism to dual/mixed on Day 5 (reverting back to X4 by Day 17).7,8 

In another 10-day monotherapy study (ACTG A5210) of twice daily AMD-070 200 mg in 6 HIV-infected adults, all 6 study participants were dual/mixed-tropic at study entry. At Day 10, all participants remained dual/mixed-tropic except for 1, who was R5-tropic.9

Dosing in Clinical Trials

AMD-070 is administered orally and twice daily.8,9

Two 10-day Phase I/II studies (participants were off antiretroviral therapy for at least 14 days; the majority of participants had dual/mixed-tropic virus at study entry):

  • X4 Antagonist Concept Trial (XACT): 100 or 200 mg twice daily (participants receiving the 100-mg dose was due to a dosing error).8,10
  • ACTG Protocol A5210: 200 mg twice daily.9
Additional dose cohorts were planned; however, because of histologic changes to the liver in long-term animal studies, AMD-070 was placed on clinical hold.8 

Adverse Events

In the XACT study, a total of six study drug-related adverse events were reported by five study participants. All except one drug-related adverse event were of grade 1 severity. The most common adverse events were mild gastrointestinal symptoms (diarrhea and flatulence) and headache. Dizziness was reported in one participant. No drug-related serious adverse events occurred. No laboratory abnormalities of grade 1 or higher were reported. Hepatotoxicity was not observed during this study.7,8 

In ACTG A5210, no adverse events of grade 3 severity or higher were observed during the 10-day treatment period or 7 days following therapy.9

Drug Interactions

AMD-070 is a substrate of both CYP3A4 and P-gp and shows potential for inhibition of CYP2D6, CYP3A4, and CYP1A2 enzymes.3

Co-administration of low-dose ritonavir with AMD-070 has been shown to cause weak increases in the Cmax and AUC of AMD-070.3

When co-administered with CYP probe drugs—midazolam (CYP3A4 substrate) and dextromethorphan (CYP2D6 substrate)—AMD-070 caused a significant increase in the AUC for both probe drugs and in the Cmax for the CYP2D6 probe.11


1. United States National Library of Medicine. ChemIDplus Advanced

2. National Institute of Allergy and Infectious Diseases (NIAID). NIAID ChemDB, HIV Drugs in Development.

3. Cao YJ, Flexner CW, Dunaway S, et al. Effect of low-dose ritonavir on the pharmacokinetics of the CXCR4 antagonist AMD070 in healthy volunteers. Antimicrob Agents Chemother. 2008 May;52(5):1630-4.

4. Wong R, Bodart V, Metz M, Labrecque J, Bridger G, Fricker S. Understanding the Interactions Between CXCR4 and AMD11070, a First-in-Class Small Molecule Antagonist of the HIV Coreceptor. Poster presented at: 14th Conference on Retroviruses and Opportunistic Infections (CROI); February 25-28, 2007; Los Angeles, CA. Poster 495.

5. Poveda E, Soriano V. Resistance to entry inhibitors. In: Geretti AM, editor. Antiretroviral Resistance in Clinical Practice. London: Mediscript; 2006. Chapter 4.

6. Stone ND, Dunaway SB, Flexner C, et al. Multiple-dose escalation study of the safety, pharmacokinetics, and biologic activity of oral AMD070, a selective CXCR4 receptor inhibitor, in human subjects. Antimicrob Agents Chemother. 2007 Jul;51(7):2351-8.

7. Moyle G, DeJesus E, Boffito M, et al. CXCR4 Antagonism: Proof of Activity with AMD11070. Poster presented at: 14th Conference on Retroviruses and Opportunistic Infections (CROI); February 25-28, 2007; Los Angeles, CA. Poster 511.

8. Moyle G, DeJesus E, Boffito M, et al. Proof of activity with AMD11070, an orally bioavailable inhibitor of CXCR4-tropic HIV type 1. Clin Infect Dis. 2009 Mar 15;48(6):798-805.

9. Saag M, Rosenkranz S, Becker S, et al. Proof of Concept of Antiretroviral Activity of AMD11070 (an Orally Administered CXCR4 Entry Inhibitor): Results of the First Dosing Cohort A Studied in ACTG Protocol A5210. Paper presented at: 14th Conference on Retroviruses and Opportunistic Infections (CROI); February 25-28, 2007; Los Angeles, CA. Paper 512.

10. Genzyme. Multicenter, Dose-finding Safety and Activity Study of AMD11070 in HIV-infected Patients Carrying X4-tropic Virus. In: Bethesda (MD): National Library of Medicine (US). Registered on August 3, 2006. NLM Identifier: NCT00361101. Last accessed May 27, 2013.

11. Nyunt M, Becker S, MacFarland R, et al. Pharmacokinetic Interaction between AMD11070 and Substrates of CYP3A4 and 2D6 Enzymes in Healthy Volunteers. Paper presented at: 14th Conference on Retroviruses and Opportunistic Infections (CROI); February 25-28, 2007; Los Angeles. CA. Paper 569.

Last Reviewed: May 28, 2013

Last Updated: May 28, 2013

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