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Pathway Description
Ibalizumab Action Pathway
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2023-06-05
Last Updated: 2023-10-25
Ibalizumab, also known as Trogarzo, is a monoclonal antibody (mAb) that inhibits the viral-entry of HIV-1. It is mostly used to treat patients with HIV-1 infection in highly treatment-experienced adults with multidrug-resistant HIV-1 infection. This drug is a CD4 domain2-directed post-attachement HIV-1 inhibitor. Since CD4 cells are the main target for HIV-1, ibalizumab creates a barrier against HIV-1 entry, also, because it is specific to the domain 2, it does not cause immunosuppression. When bound, the drug block the gp120-CD4 complex from interacting with CCR5 or CXCR4, then the viral-entry can not happen. It is due to the fact that the viral-entry requires the sequential binding of the gp120 protein with the CD4 glycoprotein and a chemokine receptor on the cell surface. This drug is available as intravenous injections.
References
Ibalizumab Pathway References
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
Kuritzkes DR, Jacobson J, Powderly WG, Godofsky E, DeJesus E, Haas F, Reimann KA, Larson JL, Yarbough PO, Curt V, Shanahan WR Jr: Antiretroviral activity of the anti-CD4 monoclonal antibody TNX-355 in patients infected with HIV type 1. J Infect Dis. 2004 Jan 15;189(2):286-91. doi: 10.1086/380802. Epub 2004 Jan 8.
Pubmed: 14722894
Vermeire K, Schols D, Bell TW: CD4 down-modulating compounds with potent anti-HIV activity. Curr Pharm Des. 2004;10(15):1795-803. doi: 10.2174/1381612043384547.
Pubmed: 15180541
Silberman SL, Goldman SJ, Mitchell DB, Tong AT, Rosenstein Y, Diamond DC, Finberg RW, Schreiber SL, Burakoff SJ: The interaction of CD4 with HIV-1 gp120. Semin Immunol. 1991 May;3(3):187-92.
Pubmed: 1888898
Jacobson JM, Kuritzkes DR, Godofsky E, DeJesus E, Larson JA, Weinheimer SP, Lewis ST: Safety, pharmacokinetics, and antiretroviral activity of multiple doses of ibalizumab (formerly TNX-355), an anti-CD4 monoclonal antibody, in human immunodeficiency virus type 1-infected adults. Antimicrob Agents Chemother. 2009 Feb;53(2):450-7. doi: 10.1128/AAC.00942-08. Epub 2008 Nov 17.
Pubmed: 19015347
Iacob SA, Iacob DG: Ibalizumab Targeting CD4 Receptors, An Emerging Molecule in HIV Therapy. Front Microbiol. 2017 Nov 27;8:2323. doi: 10.3389/fmicb.2017.02323. eCollection 2017.
Pubmed: 29230203
Song R, Franco D, Kao CY, Yu F, Huang Y, Ho DD: Epitope mapping of ibalizumab, a humanized anti-CD4 monoclonal antibody with anti-HIV-1 activity in infected patients. J Virol. 2010 Jul;84(14):6935-42. doi: 10.1128/JVI.00453-10. Epub 2010 May 12.
Pubmed: 20463063
Vila-Coro AJ, Mellado M, Martin de Ana A, Lucas P, del Real G, Martinez-A C, Rodriguez-Frade JM: HIV-1 infection through the CCR5 receptor is blocked by receptor dimerization. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3388-93. doi: 10.1073/pnas.97.7.3388.
Pubmed: 10725362
Raport CJ, Gosling J, Schweickart VL, Gray PW, Charo IF: Molecular cloning and functional characterization of a novel human CC chemokine receptor (CCR5) for RANTES, MIP-1beta, and MIP-1alpha. J Biol Chem. 1996 Jul 19;271(29):17161-6. doi: 10.1074/jbc.271.29.17161.
Pubmed: 8663314
Kuhmann SE, Platt EJ, Kozak SL, Kabat D: Polymorphisms in the CCR5 genes of African green monkeys and mice implicate specific amino acids in infections by simian and human immunodeficiency viruses. J Virol. 1997 Nov;71(11):8642-56.
Pubmed: 9343222
Zhang L, Carruthers CD, He T, Huang Y, Cao Y, Wang G, Hahn B, Ho DD: HIV type 1 subtypes, coreceptor usage, and CCR5 polymorphism. AIDS Res Hum Retroviruses. 1997 Nov 1;13(16):1357-66. doi: 10.1089/aid.1997.13.1357.
Pubmed: 9359654
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