murine hepatitis virus, delayed brain tumor cell ( EC50 = 30 nM ); SARS-CoV, HAE cell ( EC50 = 74 nM ); MERS-CoV, HAE cell ( EC50 = 74 nM ); SARS-CoV-2 ( IC50 = 3.3 μM ); SARS-CoV-2 alpha ( IC50 = 4.7 μM ); SARS-CoV-2 beta ( IC50 = 32 μM ); SARS-CoV-2 gamma ( IC50 = 3.7 μM ); SARS-CoV-2 delta ( IC50 = 9.2 μM )

GS-5734 demonstrates broad-spectrum antiviral activity against other pathogenic RNA viruses in vitro and antiviral activity against multiple EBOV variants in cell-based assays (EC50=0.06-0.14 μM).[1] With an EC50 of 0.03 μM for the murine hepatitis virus in delayed brain tumor cells and 0.074 μM for SARS-CoV and MERS-CoV in HAE cells, GS-5734 functions as a broad-spectrum therapeutic to protect against CoVs.[2]

The administration of 3 mg/kg GS-5734 results in improved survival regardless of the time at which the treatment is started. Following three days of viral exposure, all animals receiving 10 mg/kg GS-5734 treatments reach the end of their in-life phase. Animals given repeated doses of 10 mg/kg GS-5734, however, consistently exhibit stronger antiviral effects. Clinical disease signs and markers of coagulopathy and end organ pathophysiology related to EVD are associated with improvement when treated with the 10 mg/kg D3 regimen (starting 3 days after virus exposure).[1]

In vitro RSV RNA synthesis assay[1]
RNA synthesis by the RSV polymerase was reconstituted in vitro using purified RSV L/P complexes and an RNA oligonucleotide template (Dharmacon), representing nucleotides 1–14 of the RSV leader promoter31,32,33 (3′-UGCGCUUUUUUACG-5′). RNA synthesis reactions were performed as described previously, except that the reaction mixture contained 250 μM guanosine triphosphate (GTP), 10 μM uridine triphosphate (UTP), 10 μM cytidine triphosphate (CTP), supplemented with 10 μCi [α-32P]CTP, and either included 10 μM adenosine triphosphate (ATP) or no ATP. Under these conditions, the polymerase is able to initiate synthesis from the position 3 site of the promoter, but not the position 1 site. The NTP metabolite of GS-5734 was serially diluted in DMSO and included in each reaction mixture at concentrations of 10, 30, or 100 μM as specified in Fig. 1f. RNA products were analysed by electrophoresis on a 25% polyacrylamide gel, containing 7 M urea, in Tris–taurine–EDTA buffer, and radiolabelled RNA products were detected by autoradiography.

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RSV A2 polymerase inhibition assay[1]
Transcription reactions contained 25 μg of crude RSV RNP complexes in 30 μL of reaction buffer (50 mM Tris-acetate (pH 8.0), 120 mM potassium acetate, 5% glycerol, 4.5 mM MgCl2, 3 mM DTT, 2 mM EGTA, 50 μg ml−1 BSA, 2.5 U RNasin, 20 μM ATP, 100 μM GTP, 100 μM UTP, 100 μM CTP, and 1.5 μCi [α-32P]ATP (3,000 Ci mmol−1)). The radiolabelled nucleotide used in the transcription assay was selected to match the nucleotide analogue being evaluated for inhibition of RSV RNP transcription.
To determine whether nucleotide analogues inhibited RSV RNP transcription, compounds were added using a six-step serial dilution in fivefold increments. After a 90-min incubation at 30 °C, the RNP reactions were stopped with 350 μl of Qiagen RLT lysis buffer, and the RNA was purified using a Qiagen RNeasy 96 kit. Purified RNA was denatured in RNA sample loading buffer at 65 °C for 10 min and run on a 1.2% agarose/MOPS gel containing 2 M formaldehyde. The agarose gel was dried, exposed to a Storm phosphorimaging screen, and developed using a Storm phosphorimager.

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Inhibition of human RNA polymerase II[1]
For a 25 μl reaction mixture, 7.5 μl 1 × transcription buffer (20 mM HEPES (pH 7.2–7.5), 100 mM KCl, 0.2 mM EDTA, 0.5 mM DTT, 20% glycerol), 3 mM MgCl2, 100 ng CMV positive or negative control DNA, and a mixture of ATP, GTP, CTP and UTP was pre-incubated with various concentrations (0–500 μM) of the inhibitor at 30 °C for 5 min. The mixture contained 5–25 μM (equal to Km) of the competing 33P-labelled ATP and 400 μM of GTP, UTP, and CTP. The reaction was started by addition of 3.5 μl of HeLa and extract. After 1 h of incubation at 30 °C, the polymerase reaction was stopped by addition of 10.6 μl proteinase K mixture that contained final concentrations of 2.5 μg μl−1 proteinase K, 5% SDS, and 25 mM EDTA. After incubation at 37 °C for 3–12 h, 10 μl of the reaction mixture was mixed with 10 μl of the loading dye (98% formamide, 0.1% xylene cyanol and 0.1% bromophenol blue), heated at 75 °C for 5 min, and loaded onto a 6% polyacrylamide gel (8 M urea). The gel was dried for 45 min at 70 °C and exposed to a phosphorimager screen. The full length product, 363 nucleotide runoff RNA, was quantified using a Typhoon Trio Imager and Image Quant TL Software.

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Inhibition of human mitochondrial RNA polymerase[1]
Twenty nanomolar POLRMT was incubated with 20 nM template plasmid (pUC18-LSP) containing POLRMT light-strand promoter region and mitochondrial (mt) transcription factors TFA (100 nM) and mtTFB2 (20 nM) in buffer containing 10 mM HEPES (pH 7.5), 20 mM NaCl, 10 mM DTT, 0.1 mg ml−1 BSA, and 10 mM MgCl234. The reaction mixture was pre-incubated to 32 °C, and the reactions were initiated by addition of 2.5 μM of each of the natural NTPs and 1.5 μCi of [32P]GTP. After incubation for 30 min at 32 °C, reactions were spotted on DE81 paper and quantified.

EBOV assay in HeLa and HFF-1 cells[1]
Antiviral assays were conducted in BSL-4 at USAMRIID. HeLa or HFF-1 cells were seeded at 2,000 cells per well in 384-well plates. Ten serial dilutions of compound in triplicate were added directly to the cell cultures using the HP D300 digital dispenser in twofold dilution increments starting at 10 μM at 2 h before infection. The DMSO concentration in each well was normalized to 1% using an HP D300 digital dispenser. The assay plates were transferred to the BSL-4 suite and infected with EBOV Kikwit at a multiplicity of infection of 0.5 PFU per cell for HeLa cells and with EBOV Makona at a multiplicity of infection of 5 PFU per cell for HFF-1 cells. The assay plates were incubated in a tissue culture incubator for 48 h. Infection was terminated by fixing the samples in 10% formalin solution for an additional 48 h before immune-staining, as described in Supplementary Table 1.[1]

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EBOV human macrophage infection assay[1]
Antiviral assays were conducted in BSL-4 at USAMRIID. Primary human macrophage cells were seeded in a 96-well plate at 40,000 cells per well. Eight to ten serial dilutions of compound in triplicate were added directly to the cell cultures using an HP D300 digital dispenser in threefold dilution increments 2 h before infection. The concentration of DMSO was normalized to 1% in all wells. The plates were transferred into the BSL-4 suite, and the cells were infected with 1 PFU per cell of EBOV in 100 μl of media and incubated for 1 h. The inoculum was removed, and the media was replaced with fresh media containing diluted compounds. At 48 h post-infection, virus replication was quantified by immuno-staining as described in Supplementary Table 1.[1]

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RSV A2 antiviral assay[1]
For antiviral tests, compounds were threefold serially diluted in source plates from which 100 nl of diluted compound was transferred to a 384-well cell culture plate using an Echo acoustic transfer apparatus. HEp-2 cells were added at a density of 5 × 105 cells per ml, then infected by adding RSV A2 at a titer of 1 × 104.5 tissue culture infectious doses (TCID50) per ml. Immediately following virus addition, 20 μl of the virus and cells mixture was added to the 384-well cell culture plates using a μFlow liquid dispenser and cultured for 4 days at 37 °C. After incubation, the cells were allowed to equilibrate to 25 °C for 30 min. The RSV-induced cytopathic effect was determined by adding 20 μl of CellTiter-Glo Viability Reagent. After a 10-min incubation at 25 °C, cell viability was determined by measuring luminescence using an Envision plate reader.

Rhesus monkeys (Macaca mulatta)
3 mg/kg, 10 mg/kg
IV

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In vivo efficacy[1]
Rhesus monkeys (Macaca mulatta) were challenged on day 0 by intramuscular injection with a target dose of 1,000 PFU of EBOV Kikwit (Ebola virus H. sapiens-tc/COD/1995/Kikwit), which was derived from a clinical specimen obtained during an outbreak occurring in the Democratic Republic of the Congo (formerly Zaire) in 1995. Challenge virus was propagated from the clinical specimen using cultured cells (Vero or Vero E6) for a total of four passages. Animals (3–6 years old) were randomly assigned to experimental treatment groups, stratified by sex (with equal number of males and females per group) and balanced by body weight, using SAS statistical software. Study personnel responsible for assessing animal health (including euthanasia assessment) and administering treatments were experimentally blinded to group assignment of animals. The primary endpoint for efficacy studies was survival to day 28 following virus challenge. GS-5734 was formulated at Gilead Sciences in water with 12% sulfobutylether-β-cyclodextrin (SBE- β-CD), pH adjusted to 3.0 using HCl. Formulations were administered to anaesthetized animals by bolus intravenous injection at a rate of approximately 1 min per dose in the right or left saphenous vein. The volume of all vehicle or GS-5734 injections was 2.0 ml kg−1 body weight. Animals were anaesthetized using intramuscular injection of a solution containing ketamine (100 mg ml−1) and acepromazine (10 mg ml−1) at 0.1 ml kg−1 body weight.[1]
Animals were observed at least twice daily to monitor for disease signs, and animals that survived to day 28 were deemed to be protected. Study personnel alleviated unnecessary suffering of infected animals by euthanizing clinically moribund animals. The criteria used as the basis for euthanasia of moribund animals were defined before study initiation and included magnitude of responsiveness, reduced body temperature, and/or specified alterations to serum chemistry parameters35. Serum chemistry was analysed using a Vitros 350 Chemistry System, and coagulation parameters were evaluated using a Sysmex CA-1500 coagulation analyser. Haematology analysis was conducted using a Siemens Advia 120 Hematology System with multispecies software. On days in which GS-5734 or vehicle dosing were scheduled with blood sample collection for clinical pathology or viraemia analysis, blood samples were collected immediately before dose administration.[1]

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Pharmacokinetic evaluations[1]
Three uninfected male rhesus monkeys were used for the pharmacokinetic study. GS-5734 was formulated in solution at 5 mg ml−1 with 12% sulfobutylether-β-cyclodextrin in water, pH 3.5–4.0, and 2 ml kg−1 was administered by slow bolus (approximately 1 min) for a final dose of 10 mg kg−1. Blood samples for plasma and PBMCs were collected from a femoral vein/artery and were taken from each monkey over a 24-h period. Plasma samples were obtained at predose and at 0.083, 0.25, 0.5, 1, 2, 4, 8, and 24 h postdose. PBMC samples were obtained at 2, 4, 8, and 24 h. Blood samples for plasma were collected into chilled collection tubes containing sodium fluoride/potassium oxalate as the anticoagulant and were immediately placed on wet ice, followed by centrifugation to obtain plasma. Blood samples for PBMC isolation were collected at room temperature into CPT vacutainer tubes containing sodium heparin for isolation. Plasma and isolated PBMC samples were frozen immediately and stored at ≤60 °C until analysed.[1]
For plasma analysis, an aliquot of 25 μl of each plasma sample was treated with 100 μl of 90% methanol and acetonitrile mixture (1:1, v:v) and 10% water with 20 nM 5-(2-aminopropyl)indole as an internal standard. Then, 100 μl of samples were filtered through an Agilent Captiva 96 well 0.2 μm filter plate. Filtered samples were dried down completely for approximately 20 min and reconstituted with 1% acetonitrile and 99% water with 0.01% formic acid. An aliquot of 10 μl was injected for LC-MS/MS using a HTC Pal autosampler. Analytes were separated on a Phenomenex Synergi Hydro-RP 30A column (75 × 2.0 mM, 4.0 μm) using a Waters Acquity ultra performance LC, a flow rate of 0.26 ml min−1, and a gradient from Mobile phase A containing 0.2% formic acid in 99% water and 1% acetonitrile to mobile phase B containing 0.2% formic acid in 95% acetonitrile and 5% water over 4.5 min. For MS/MS analysis, we used a Waters Xevo TQ-S in positive multiple reaction monitoring mode using an electrospray probe. Plasma concentrations of GS-734, alanine metabolite and Nuc were determined using an 8-point calibration curve spanning a concentration range of over three orders of magnitude. Quality control samples were run at the beginning and end of the run to ensure accuracy and precision within 20%. Intracellular metabolites in PBMCs were quantified by LC-MS/MS as described above for in vitro activation studies.[1]

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Radiolabelled tissue distribution[1]
Six cynomolgus monkeys were administered a single dose of [14C]GS-5734 at 10 mg kg−1 (25 μCi kg−1) by intravenous administration (slow bolus). Tissues were collected from three animals at 4 and 168 h postdose. The tissues were excised, rinsed with saline, blotted dry, weighed, and placed on wet ice. Tissues (testes, epididymis, eyes and brain; following homogenization) and plasma were analysed by liquid scintillation counting. Concentrations were converted to ng equivalents of GS-5734 per gram of sample.

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Assessment of resistant virus virulence in vivo. [2]
Groups of 10 to 12 10-week old female BALB/c (Charles River, Inc.) mice were anesthetized with ketamine-xylazine and intranasally infected with either 104 or 103 PFU/50 µl wild-type mouse-adapted SARS-CoV expressing nanoluciferase (WT SARS-CoV) or SARS-MA15 NanoLuc engineered to harbor resistance mutations in nsp12 (F480L + V557L SARS-CoV). Animals were weighed daily to monitor virus-associated weight loss. On days 2 and 4 postinfection, 5 to 6 animals per group were sacrificed by isoflurane overdose and the inferior right lobe was harvested and frozen at −80°C until the titer was determined by plaque assay as described previously (38). A 5- to 6-animal cohort was monitored out to 7 days postinfection in order to compare the kinetics of recovery, after which lung samples were harvested and the titer determined as described for previous samples.

Absorption, Distribution and Excretion
Remdesivir is absorbed quickly; maximal plasma concentrations following a single 30-minute intravenous infusion are reached within 0.67-0.68 hours (Tmax). Repeated dosing yields a Cmax (coefficient of variation as a percent) of 2229 (19.2) ng/mL and an AUCtau of 1585 (16.6) ng\*h/mL. Remdesivir metabolite [GS-441524] has measured values: Tmax 1.51-2.00 hours, Cmax 145 (19.3) ng/mL, AUCtau 2229 (18.4) ng\*h/mL, and Ctrough 69.2 (18.2) ng/mL. Another metabolite, GS-704277, has measured values: Tmax 0.75 hours, Cmax 246 (33.9) ng/mL, AUCtau 462 (31.4) ng\*h/mL, and an undetermined Ctrough. A 10mg/kg intravenous dose given to cynomolgus monkeys distributes to the testes, epididymis, eyes, and brain within 4h.
Remdesivir is 74% eliminated in the urine and 18% eliminated in the feces. 49% of the recovered dose is in the form of the metabolite [GS-441524], and 10% is recovered as the unmetabolized parent compound. A small amount (0.5%) of the [GS-441524] metabolite is found in feces.
Data regarding the volume of distribution of remdesivir is not readily available.
Data regarding the clearance of remdesivir is not readily available.

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Metabolism / Metabolites
Remdesivir is a phosphoramidate prodrug that must be metabolized within host cells to its triphosphate metabolite to be therapeutically active. Upon cell entry, remdesivir is presumed to undergo first esterase-mediated hydrolysis to a carboxylate form followed by cyclization to eject the phenoxide moiety and finally hydrolysis of the cyclic anhydride to yield the detectable alanine metabolite (GS-704277). The alanine metabolite is subsequently hydrolyzed to yield the monophosphate form of remdesivir, which is either hydrolyzed again to yield the bare nucleoside metabolite [GS-441524] or phosphorylated by cellular kinases to yield the active triphosphate form.

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Biological Half-Life
Remdesivir has an elimination half-life of 1 hour following a single 30-minute intravenous infusion. Under the same conditions, the elimination half-lives of the remdesivir metabolites [GS-441524] and GS-704277 are 27 hours and 1.3 hours, respectively. A 10mg/kg intravenous dose in non-human primates has a plasma half-life of 0.39h. The nucleoside triphosphate metabolite has a half-life of 14h in non-human primates. The nucleoside triphosphate metabolite has a half-life of approximately 20 hours in humans.

Hepatotoxicity
In human volunteer studies, remdesivir therapy given for 7 to 14 days was associated with minor serum aminotransferase elevations (less than 5 times ULN) but without other evidence of hepatic injury. In controlled trials of remdesivir in patients hospitalized with COVID-19, rates of serum ALT elevations were similar or lower in patients receiving remdesivir than in those on placebo. Nevertheless, in most uncontrolled studies and case series, between 10% and 50% of patients treated with remdesivir developed transient, mild-to-moderate serum ALT and AST elevations within 1 to 5 days of starting therapy without changes in serum bilirubin or alkaline phosphatase levels. Elevations above 5 times ULN were reported in up to 9% of patients in several clinical trials, but the abnormalities resolved with discontinuation and were not associated with clinically apparent injury. With more widespread use of remdesivir for COVID-19, rare instances of marked ALT elevations with jaundice have been reported, but largely in patients who were critically ill with multi-organ failure or sepsis, or who had received other potentially hepatotoxic agents such as intravenous amiodarone (Case 2). Confounding the issue is that serum aminotransferase elevations are common during symptomatic SARS-CoV-2 infection (Case 1), present in up to 60% of patients and being more frequent in patients with severe disease and in those with the known risk factors for COVID-19 severity such as male sex, older age, higher body mass index and diabetes. Thus, serum aminotransferase elevations are common during remdesivir therapy but are generally asymptomatic, fully reversible and not associated with jaundice. With more widespread use of this antiviral in patients without severe or critical illness and with longer courses of therapy, features of hepatotoxicity may become more evident.
Likelihood score: D (possible uncommon cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Information from 5 patients indicate that milk levels of remdesivir and its active metabolite are very low in milk. Additionally, remdesivir is poorly absorbed orally, and the metabolite is only partially absorbed orally, so infants are not likely to absorb clinically important amounts of the drug from milk. Newborn infants have received intravenous remdesivir therapy for Ebola and for COVID-19 with no serious adverse drug reactions and it is FDA approved for use in infants of at least 28 days and weighing 3 kg. Infants exposed via breastmilk have also not had any reported adverse reactions. Given this information, mothers receiving remdesivir do not need to avoid nursing, but until more data are available, remdesivir should be used with careful infant monitoring during breastfeeding. The most common adverse effects reported after intravenous infusion include elevated aminotransferase and bilirubin levels and other liver enzyme elevations, diarrhea, rash, renal impairment and hypotension.
◉ Effects in Breastfed Infants
The manufacturer reports that 11 breastfed infants were exposed to remdesevir in breastmilk from pharmacovigilance reports. The reports do not indicate adverse effects on breastfed infants from exposure to remdesivir and its metabolite through breastmilk.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.
◈ What is remdesivir?
Remdesivir is an antiviral medication approved to treat SARS-CoV-2 virus, which causes COVID-19. Remdesivir may also be used to treat Ebola virus infections. Remdesivir is sold under the brand name Veklury®. For more information about COVID-19, please see the MotherToBaby fact sheet at https://mothertobaby.org/fact-sheets/covid-19/.Sometimes when people find out they are pregnant, they think about changing how they take their medication, or stopping their medication altogether. However, it is important to talk with your healthcare providers before making any changes to how you take this medication. Your healthcare providers can talk with you about the benefits of treating your condition and the risks of untreated illness during pregnancy.
◈ I take remdesivir. Can it make it harder for me to get pregnant?
Studies have not been done to see if remdesivir could make it harder to get pregnant.
◈ Does taking remdesivir increase the chance for miscarriage?
Miscarriage can occur in any pregnancy. Studies have not been done to see if remdesivir increases the chance for miscarriage.
◈ Does taking remdesivir increase the chance of birth defects?
Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk. Based on the studies reviewed, it is not known if remdesivir increases the chance for birth defects above the background risk. Animal studies have not shown an increased chance for birth defects. There are no human studies looking at the chance for birth defects with remdesivir use in pregnancy.
◈ Does taking remdesivir in pregnancy increase the chance of other pregnancy related problems?
Based on reports of 70 people who were treated with remdesivir for COVID-19 infections in the second and third trimesters of pregnancy, there was a higher chance for preterm delivery (birth before week 37), low birth weight (weighing less than 5 pounds, 8 ounces [2500 grams] at birth), and cesarean section. However, these people were also very ill with COVID-19. Pregnancy related problems, including preterm birth, have also been associated with COVID-19 infection in pregnancy. Based on these reports, it is not yet clear if these outcomes were due to the COVID-19 illness, the medication, or a combination of both.One study looked at 39 people who were pregnant and treated with remdesivir for COVID-19 infections and compared them to 56 people who were pregnant but were not treated with remdesivir for their COVID-19 infections. This study showed that the rate of preterm delivery was similar between those two groups. This suggests that the COVID-19 illness is what might increase the chance for preterm delivery, not the medication.
◈ Does taking remdesivir in pregnancy affect future behavior or learning for the child ?
Studies have not been done to see if remdesivir causes long-term behavior or learning problems. There are reports of newborns diagnosed with Ebola and COVID-19 who were treated directly with remdesivir. These babies had no reported serious reactions to remdesivir. The child who was treated with remdesivir for Ebola was reported to have appropriate weight and development at one year of age.
◈ Breastfeeding while taking remdesivir:
Based on 1 case report, levels of remdesivir in milk seem to be very low. Remdesivir is also poorly absorbed when given by mouth (orally). This means nursing infants are not likely to absorb large amounts of the medication from milk. Reports from two newborn babies that were given remdesivir after birth to treat Ebola and COVID-19 did not have any reactions to the medications.Because there is very limited information about remdesivir use during breastfeeding, if remdesivir is used during breastfeeding, a healthcare provider may watch for issues with the way the baby’s liver and kidneys works, the baby’s blood pressure, and for diarrhea or rash. If you suspect the baby has any reaction or symptoms, contact the child’s healthcare provider. If a person wants to breastfeed but cannot due to feeling very ill from COVID-19, they can work with their healthcare provider or lactation consultant to help establish or keep up their milk supply for breastfeeding once they feel better. Be sure to talk to your healthcare provider about all of your breastfeeding questions.
◈ If a male takes remdesivir, could it affect fertility (ability to get partner pregnant) or increase the chance of birth defects?
Studies have not been done to see if remdesivir affects fertility. In general, exposures that fathers or sperm donors have are unlikely to increase risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.

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Protein Binding
Remdesivir is 88-93.6% bound to human plasma proteins while its metabolites [GS-441524] and GS-704277 are 2% and 1% bound, respectively.

[1]. Nature . 2016 Mar 17;531(7594):381-5.

[2]. mBio . 2018 Mar 6;9(2):e00221-18.

Pharmacodynamics
Remdesivir is a nucleoside analog used to inhibit the action of RNA polymerase. The duration of action is moderate, as it is given once daily. Due to much higher selectivity of mammalian DNA and RNA polymerases, including human mitochondrial RNA polymerase, for ATP over remdesivir triphosphate, remdesivir is not a significant inhibitor of these enzymes, which contributes to its overall tolerability and safety profile. Despite this, remdesivir carries risks for hypersensitivity reactions, including anaphylaxis and other infusion-related reactions, elevated transaminase levels, and potential decreased efficacy when combined with [hydroxychloroquine] or [chloroquine].

C27H35N6O8P

602.5760

602.225

C, 53.82; H, 5.85; N, 13.95; O, 21.24; P, 5.14

1809249-37-3

1355149-45-9 [GS443902 (GS-441524 triphosphate)]; 1809249-37-3 (Remdesivir); 1191237-69-0 (GS-441524, an active metabolite of Remdesivir); 1191237-80-5 (Remdesivir O-desphosphate acetonide impurity); 1911578-74-9 (Remdesivir nucleoside monophosphate); 2250110-53-1;1911579-04-8 (GS-704277)

121304016

Off-white to yellow solid powder

1.5±0.1 g/cm3

1.652

2.1

4

13

14

42

1010

6

[P@@](N([H])[C@@]([H])(C([H])([H])[H])C(=O)OC([H])([H])C([H])(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])[H])(=O)(OC1C([H])=C([H])C([H])=C([H])C=1[H])OC([H])([H])[C@]1([H])[C@]([H])([C@]([H])([C@](C#N)(C2=C([H])C([H])=C3C(N([H])[H])=NC([H])=NN23)O1)O[H])O[H]

RWWYLEGWBNMMLJ-YSOARWBDSA-N

InChI=1S/C27H35N6O8P/c1-4-18(5-2)13-38-26(36)17(3)32-42(37,41-19-9-7-6-8-10-19)39-14-21-23(34)24(35)27(15-28,40-21)22-12-11-20-25(29)30-16-31-33(20)22/h6-12,16-18,21,23-24,34-35H,4-5,13-14H2,1-3H3,(H,32,37)(H2,29,30,31)/t17-,21+,23+,24+,27-,42-/m0/s1

2-ethylbutyl (2S)-2-[[[(2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxyoxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate

GS-5734; GS 5734; Prodrug of GS441524; Prodrug of GS441524; Remdesivir; GS5734; Prodrug of GS-441524; 3QKI37EEHE; GS 5734; GS 5734 [WHO-DD]; GS-5734; GS5734; Remdesivir; REMDESIVIR [INN];

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~100 mg/mL (~166 mM)
Ethanol: ~100 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.15 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.17 mg/mL (3.60 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.17 mg/mL (3.60 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 21.7 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 5%DMSO+ 40%PEG300+ 5%Tween 80+ 50%ddH2O: 5.0mg/ml (8.30mM)

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 (Please use freshly prepared in vivo formulations for optimal results.)