BMS-378806, also known as BMS-806, is a type of medicine called an entry inhibitor. Entry inhibitors work by blocking HIV from entering human cells.
HIV/AIDS-Related Uses
BMS-378806 is an investigational medicine that is not yet approved by the FDA for use outside of clinical trials. It is being studied for the treatment and prevention of HIV infection. This medicine does not cure HIV infection or AIDS and is being studied to reduce the risk of passing the virus to other people.
Dosage Form/Administration
BMS-378806 has been studied in oral form to be taken by mouth and also comes in a vaginal gel.
Contraindications
Individuals should tell a doctor about any medical problems before taking this medicine.
Possible Side Effects
Along with its desired effects, BMS-378806 may cause some unwanted effects. More studies are needed to learn about BMS-378806's possible side effects.
Drug and Food Interactions
A doctor should be notified of any other medications being taken, including prescription, nonprescription (over-the-counter), or herbal medications.
Clinical Trials
Click here to search ClinicalTrials.gov for trials that use BMS-378806.
Manufacturer Information
BMS-378806
Bristol - Myers Squibb Co
PO Box 4500
Princeton, NJ 08543-4500
Phone: 800-321-1335
Last Updated: June 6, 2008
Drug Description
BMS-378806, or BMS-806, is a small molecule entry inhibitor of HIV-1 that targets the viral envelope protein. [1] [2]
References
[1] AIDS 2004 NOV 19;18:2327-30
[2] Antivir Ther 2002;7(Suppl 1):S1-251
HIV/AIDS-Related Uses
BMS-378806 is being investigated for the treatment of subtype B HIV-1 infection, including both CCR5 and CXR4 strains. [1] BMS-378806 is also being investigated in formulations for vaginal administration for the prevention of HIV-1 transmission when used in combination with other vaginal microbicides. [2]
References
[1] AIDS AIDS - 2004 NOV 19;18:2327-30
[2] Nature Nature - 2005 Nov 3;438(7064):99-102
Dosing Information
Mode of Delivery
Topical. [1]
Dosage Form
Vaginal gel for topical use. [2]
References
[1] Proc Natl Acad Sci USA 2003;100(19):11013-8
[2] Proc Natl Acad Sci USA 2003;100(19):11013-8
Pharmacology
BMS-378806 targets viral entry by inhibiting the binding of HIV-1 gp120 to the CD4 receptor. The affinity of BMS-378806 for the gp120 molecule is similar to that of soluble CD4 cells, and binding occurs close to the CD4 cell-binding pocket. [1] Binding of gp120 is the first step of HIV infection at the cellular level; BMS-378806 appears to be the first compound to block this binding. [2]
BMS-378806 shows good oral bioavailability in animals and has low protein binding. It is active against viral strains with both the CCR5 and the CXCR4 coreceptors and is selective for HIV-1, specifically subtype B. [3] [4]
BMS-378806 retains activity against HIV strains resistant to protease inhibitors and reverse transcriptase inhibitors. [5] Resistance maps to substitutions located primarily near the CD4 binding sites of gp120, including A204D, F423Y, M434/I/V/T, and M475I. Other reported mutations include M475I, M434I/V, M426L, D350K, D185N, K655E, 1595F, V68A, and S440R. [6]
BMS-378806 has recently been tested as a topically administered vaginal microbicide in combination with other investigational entry inhibitors. BMS-378806 and CMPD 167 appear to be synergistic in vitro, inhibiting different stages of the viral-cell attachment and entry process. [7] When combined in vitro, CMPD167, C52L, and BMS-378806 inhibited infection of T cells and cervical tissue explants. Significant protection was achieved in macaques when BMS-378806 was used alone and in combination, even when applied up to 6 hours before challenge. [8] [9]
References
[1] AIDS 2004 NOV 19;18:2327-30
[2] Proc Natl Acad Sci USA 2003;100(19):11013-8
[3] AIDS 2004 NOV 19;18:2327-30
[4] Proc Natl Acad Sci USA 2003;100(19):11013-8
[5] Antivir Ther 2002;7(Suppl 1):S1-251
[6] AIDS 2004 NOV 19;18:2327-30
[7] Nature 2005 Nov 3;438(7064):99-102
[8] Nature 2005 Nov 3;438(7064):99-102
[9] Bristol-Myers Squibb Merck and Bristol-Myers Squibb License New AIDS Drugs to IPM for Development as Microbicides to Protect Women from HIV [press release], October 31, 2005. Available at: http://newsroom.bms.com/article_display.cfm?article_id=5024. Accessed 06/06/08.
Adverse Events/Toxicity
BMS-378806 displayed an excellent safety profile in animal studies. [1] No significant cytotoxicity has been noted. [2]
References
[1] Proc Natl Acad Sci USA 2003;100(19):11013-8
[2] Antivir Ther 2002;7(Suppl 1):S1-251
Clinical Trials
Click here to search ClinicalTrials.gov for trials that use BMS-378806.
Chemistry
CAS Name
Piperazine, 4-benzoyl-1-(2-(4-methoxy-1H-pyrrolo(2,3-b) pyridin-3-yl)-1,2-dioxoethyl)-2-methyl-, (2R)- [1]
CAS Number
357263-13-9 [2]
Molecular Formula
C22-H22-N4-O4
Elemental Composition
C65%,H5.4%,N13.8%,O15.8%
Molecular Weight
406
References
[1] ChemIDplus Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp. Accessed 06/06/08.
[2] ChemIDplus Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp. Accessed 06/06/08.
Further Reading
Ketas TJ, Schader SM, Zurita J, Teo E, Polonis V, Lu M, Klasse PJ, Moore JP. Entry inhibitor-based microbicides are active in vitro against HIV-1 isolates from multiple genetic subtypes. Virology. 2007 Aug 1;364(2):431-40. Epub 2007 Apr 10.
Lin, PR. A Small Molecule HIV-1 Inhibitor That Targets the HIV-1 Envelope and Inhibits CD4 Receptor Binding. Proc Natl Acad Sci USA 2003;100(19):11013-8.
Veazey RS, Klasse PJ, Schader SM, Hu Q, Ketas TJ, Lu M, Marx PA, Dufour J, Colonno RJ, Shattock RJ, Springer MS, Moore JP. Protection of macaques from vaginal SHIV challenge by vaginally delivered inhibitors of virus-cell fusion. Nature 2005 Nov 3;438(7064):99-102.
Madani N, Hubicki A, Ng D, Smith A, Sodroski J. The road to finding potent HIV-1 entry inhibitors: Lessons learned from requirements for BMS-806 binding to HIV-1 envelope glycoprotein. 16th International AIDS Conference, Toronto, Canada, Abstract MOPE0001, 2006.
Manufacturer Information
BMS-378806
Bristol - Myers Squibb Co
PO Box 4500
Princeton, NJ 08543-4500
Phone: 800-321-1335
Last Updated: June 6, 2008