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Presatovir

Names

[ CAS No. ]:
1353625-73-6

[ Name ]:
Presatovir

[Synonym ]:
UNII-9628AJ27JA
GS-5806
presatovir
N-(2-{[(2S)-2-{5-[(3S)-3-Amino-1-pyrrolidinyl]-6-methylpyrazolo[1,5-a]pyrimidin-2-yl}-1-piperidinyl]carbonyl}-4-chlorophenyl)methanesulfonamide
Methanesulfonamide, N-[2-[[(2S)-2-[5-[(3S)-3-amino-1-pyrrolidinyl]-6-methylpyrazolo[1,5-a]pyrimidin-2-yl]-1-piperidinyl]carbonyl]-4-chlorophenyl]-
9628AJ27JA

Biological Activity

[Description]:

Presatovir (GS-5806) is a novel, orally bioavailable RSV fusion inhibitor with a mean EC50 value of 0.43 nM.

[Related Catalog]:

Signaling Pathways >> Anti-infection >> RSV
Research Areas >> Infection

[Target]

EC50: 0.43 nM (RSV)[1]


[In Vitro]

Presatovir is a novel, orally bioavailable RSV fusion inhibitor discovered following a lead optimization campaign on a hit originated from a phenotypic RSV antiviral high-throughput screen. Presatovir exhibits potent activity against a wide range of RSV A and B clinical isolates with a mean EC50 value of 0.43 nM[1]. GS-5806 inhibits pre to post triggered conformational changes of RSV F protein, suggesting a possible mechanism for antiviral activity[2].

[In Vivo]

Presatovir demonstrates dose-dependent (0-30 mg/kg) antiviral efficacy in a cotton rat model of RSV infection. Oral bioavailability in preclinical species ranges from 46 to 100%, with penetration of the compound into the lung tissue demonstrated in Sprague-Dawley rats. Multidose oral treatment of Presatovir appears safe in adults, and in healthy human volunteers experimentally infected with RSV, a potent antiviral effect and reduction in disease severity is observed in the high dose group. A group treated with a lower dose of Presatovir allows for a PK-PD relationship to be established to help guide future dose selections[1].

[Cell Assay]

GS-5806 are diluted in 100% DMSO. To conduct the cytopathic antiviral assay, 0.4 μL of 100×concentrated 3-fold serially diluted drug is added to 20 μL of cell culture medium in a 384-well plate. HEp-2 cells are then suspended in MEM plus 10% FBS at a density of 1×105 cells/mL, are infected in bulk with RSV A2 at a titer of approximately 1×104.5 tissue culture infectious doses/mL. Immediately following infection, 20 μL of RSV-infected cells are added to each well. The cells are then cultured for 4 days at 37 °C. Following this incubation the cells are allowed to equilibrate to 25°C. The RSV-induced cytopathic effect is determined by adding 40 μL of Cell-Titer Glo viability reagent. Following a 10 min incubation at 25 °C, cell viability is determined[1].

[References]

[1]. Mackman RL, et al. Discovery of an oral respiratory syncytial virus (RSV) fusion inhibitor (GS-5806) and clinical proof of concept in a human RSV challenge study. J Med Chem. 2015 Feb 26;58(4):1630-1643.

[2]. Samuel D, et al. GS-5806 inhibits pre- to postfusion conformational changes of the respiratory syncytial virus fusion protein. Antimicrob Agents Chemother. 2015 Nov;59(11):7109-12.


[Related Small Molecules]

ALS-8112 | TMC353121 | Ac-CoA Synthase Inhibitor1 | RSV-604 | RSV-IN-1 | PC786 | RD3-0028

Chemical & Physical Properties

[ Density]:
1.5±0.1 g/cm3

[ Molecular Formula ]:
C24H30ClN7O3S

[ Molecular Weight ]:
532.058

[ Exact Mass ]:
531.181946

[ LogP ]:
1.79

[ Index of Refraction ]:
1.735

[ Storage condition ]:
2-8℃

Related Compounds