fostemsavir   Click here for help

GtoPdb Ligand ID: 11100

Abbreviated name: FTR
Synonyms: BMS-663068 | BMS663068 | compound 35 [PMID: 29271653] | GSK-3684934 | GSK3684934 | Rukobia®
Approved drug
fostemsavir is an approved drug (FDA (2020), EMA (2021))
Compound class: Synthetic organic
Comment: Fostemsavir is a phosphonooxymethyl prodrug of temsavir (BMS-626529) [4-5]. It is classified as an attachment inhibitor [2]. Temsavir binds to HIV envelope glycoprotein 120 (gp120) and thereby blocks viral attachment to the host CD4 molecule on T-lymphocytes. Naturally ocurring HIV-1 gp120 polymorphisms that could impart resistance to fostemsavir are uncommon [1].
2D Structure
Click here for help

2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

✖
Hydrogen bond acceptors 12
Hydrogen bond donors 2
Rotatable bonds 10
Topological polar surface area 191.5
Molecular weight 583.16
XLogP 0.13
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
Click here for help

SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

✖
Canonical SMILES COc1cnc(c2c1c(cn2COP(=O)(O)O)C(=O)C(=O)N1CCN(CC1)C(=O)c1ccccc1)n1cnc(n1)C
Isomeric SMILES COc1cnc(c2c1c(cn2COP(=O)(O)O)C(=O)C(=O)N1CCN(CC1)C(=O)c1ccccc1)n1cnc(n1)C
InChI InChI=1S/C25H26N7O8P/c1-16-27-14-32(28-16)23-21-20(19(39-2)12-26-23)18(13-31(21)15-40-41(36,37)38)22(33)25(35)30-10-8-29(9-11-30)24(34)17-6-4-3-5-7-17/h3-7,12-14H,8-11,15H2,1-2H3,(H2,36,37,38)
InChI Key SWMDAPWAQQTBOG-UHFFFAOYSA-N
References
1. Bouba Y, Berno G, Fabeni L, Carioti L, Salpini R, Aquaro S, Svicher V, Perno CF, Ceccherini-Silberstein F, Santoro MM. (2020)
Identification of gp120 polymorphisms in HIV-1 B subtype potentially associated with resistance to fostemsavir.
J Antimicrob Chemother, 75 (7): 1778-1786. [PMID:32160290]
2. Cahn P, Fink V, Patterson P. (2018)
Fostemsavir: a new CD4 attachment inhibitor.
Curr Opin HIV AIDS, 13 (4): 341-345. [PMID:29771694]
3. Kozal M, Aberg J, Pialoux G, Cahn P, Thompson M, Molina JM, Grinsztejn B, Diaz R, Castagna A, Kumar P et al.. (2020)
Fostemsavir in Adults with Multidrug-Resistant HIV-1 Infection.
N Engl J Med, 382 (13): 1232-1243. [PMID:32212519]
4. Lagishetty C, Moore K, Ackerman P, Llamoso C, Magee M. (2020)
Effects of Temsavir, Active Moiety of Antiretroviral Agent Fostemsavir, on QT Interval: Results From a Phase I Study and an Exposure-Response Analysis.
Clin Transl Sci, 13 (4): 769-776. [PMID:32027457]
5. Meanwell NA, Krystal MR, Nowicka-Sans B, Langley DR, Conlon DA, Eastgate MD, Grasela DM, Timmins P, Wang T, Kadow JF. (2018)
Inhibitors of HIV-1 Attachment: The Discovery and Development of Temsavir and its Prodrug Fostemsavir.
J Med Chem, 61 (1): 62-80. [PMID:29271653]