2. Anti-infection
  3. Arenavirus
  4. ARN-75039

ARN-75039 is an orally active arenavirus inhibitor. ARN-75039 binds to sites on the GP2 subunit of the mammarenavirus glycoprotein complex, stabilizes prefusion conformation, and blocks viral entry and endosomal membrane fusion to inhibit viral replication and spread. ARN-75039 can be used for the research of lassa fever, arenaviral hemorrhagic fever, and lethal Junín virus infection.

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ARN-75039

ARN-75039 Chemical Structure

CAS No. : 2436472-47-6

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Description

ARN-75039 is an orally active arenavirus inhibitor. ARN-75039 binds to sites on the GP2 subunit of the mammarenavirus glycoprotein complex, stabilizes prefusion conformation, and blocks viral entry and endosomal membrane fusion to inhibit viral replication and spread. ARN-75039 can be used for the research of lassa fever, arenaviral hemorrhagic fever, and lethal Junín virus infection[1][2][3].

In Vitro

ARN-75039 (1 h pretreatment) potently inhibits WT LASV and GPA LASV replication in Vero E6 cells with EC90 values ranging from 1.26 to 46 nM, is noncytotoxic at concentrations up to 25 μM, and has high selectivity indices for both viruses[1].
ARN-75039 (24 h) potently inhibits entry of pGTOV (EC50 = 0.13 nM), pCHAPV (EC50 = 4.3 nM), and pTCRV (EC50 = 0.22 nM) into Vero cells[2].
ARN-75039 (5 days) potently inhibits native TCRV replication in Vero cells with an EC50 of 0.75 nM and a selectivity index of 11,150[2].
ARN-75039 (24 h) inhibits wild-type pTCRV entry into Vero cells with an EC50 of 0.2 nM, while TCRV GP2 mutations E411K/H438R, I418N, and S433G/H438R confer complete resistance, and the T434I mutation confers partial resistance to ARN-75039[2].
ARN-75039 (5 days) has a CC50 of 8362 nM in Vero cells, resulting in a high selectivity index of 11,150 relative to its anti-TCRV activity[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

ARN-75039 Related Antibodies
In Vivo

ARN-75039 (3.75-60 mg/kg; p.o.; once daily for 14 days) provides 100% survival protection against lethal guinea pig-adapted Lassa virus infection in outbred Hartley guinea pigs, with minimal clinical signs and substantial viral load reduction[1].
ARN-75039 (60 mg/kg loading dose; 7.5-30 mg/kg maintenance dose; p.o.; single loading dose at 7 dpe, twice daily maintenance doses for 13 days) provides 100% survival protection against lethal guinea pig-adapted Lassa virus infection in outbred Hartley guinea pigs, with minimal clinical signs and complete viral clearance by study end[1].
ARN-75039 (10-35 mg/kg; p.o.; daily; 12 days) administered prophylactically provides 100% survival protection against lethal TCRV infection in AG129 mice and completely clears viral infection from serum and tissues[2].
ARN-75039 (20-50 mg/kg; p.o.; daily; 12 days) administered therapeutically provides up to 100% survival protection against lethal TCRV infection in AG129 mice, even when treatment starts up to 7 days post-infection, and completely clears viral infection from serum and tissues[2].
ARN-75039 (60 mg/kg; p.o.; daily; starting 2 days post-challenge) administered starting 2 or 5 days post-JUNV challenge provides 100% survival in Hartley guinea pigs[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: outbred Hartley (6-week-old; male and female; inoculated intraperitoneally with 10,000 PFU of guinea pig-adapted Lassa virus)[1]
Dosage: 3.75 mg/kg; 7.5 mg/kg; 15 mg/kg; 30 mg/kg; 60 mg/kg
Administration: p.o.; once daily; 14 days
Result: Achieved 100% survival across the 3.75 to 60 mg/kg dose range (excluding one animal in the 15 mg/kg group with suspected unrelated comorbidities).
Maintained clinical scores of 0 or showed only temporary mild clinical signs (score of 1 for ~4 days).
Rendered plasma viremia undetectable.
Reduced infectious virus titers in spleen by 4 to 5 logs compared with placebo-treated animals, with undetectable infectious virus in all other tissues.
Reduced viral genomic RNA copies in tissues by 2 to 5 logs compared with placebo-treated animals.
Showed no LASV-related pathological lesions in most treated animals, with minimal severity in those that had lesions compared with placebo-treated animals.
Animal Model: outbred Hartley (6-week-old; male and female; inoculated intraperitoneally with 10,000 PFU of guinea pig-adapted Lassa virus)[1]
Dosage: 7.5 mg/kg; 15 mg/kg; 30 mg/kg; 60 mg/kg
Administration: p.o.; single loading dose at 7 dpe, twice daily maintenance doses for 13 days; total 14 days
Result: Achieved 100% survival at the 7.5 mg/kg twice-daily dose.
Showed only mild clinical signs (score of 1) for 3 to 5 days before returning to 0, with no weight loss in the 7.5 mg/kg twice-daily group.
Rendered plasma viremia undetectable.
Reduced infectious virus titers in spleen (up to 6.4 × 104 PFU/mL) compared with placebo-treated animals, with undetectable infectious virus in most tissues.
Reduced viral genomic RNA copies in tissues significantly (P ≤ 0.003) compared with placebo-treated animals.
Detected no infectious virus in any plasma or tissue samples from surviving treated animals at terminal necropsy, with minimal or absent pathological lesions compared with placebo-treated animals.
Animal Model: AG129 (IFN-α/β and γ receptor-deficient; 6 to 8-week-old; male and female; Tacaribe virus challenge)[2]
Dosage: 10 mg/kg; 35 mg/kg
Administration: p.o.; daily; 12 days
Result: Provided 100% survival protection against TCRV-associated mortality.
Showed little to no weight loss during acute infection.
Achieved undetectable TCRV titers in serum, liver, and spleen samples on day 9 post-infection.
Resulted in undetectable TCRV titers in serum, liver, spleen, and brain at study termination, indicating complete clearance of infection.
Animal Model: Hartley (4- to 6-week-old, equal numbers of male and female)[3]
Dosage: 60 mg/kg
Administration: p.o.; daily; starting 2/5 days post-challenge
Result: Provided complete protection (100% survival) against lethal JUNV disease.
Molecular Weight

414.54

Formula

C27H30N2O2
CAS No.
Appearance

Solid

SMILES

CC1=CC2=NC=C(N2C=C1C3=CC=C(C=C3)OC(C)C)C4=CC=C(C=C4)OC(C)(C)C
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Store at room temperature 3 years

In solvent -80°C 2 years
-20°C 1 year
Purity & Documentation
References
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ARN-75039 Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

ARN-750392436472-47-6ARN75039ARN 75039ArenavirusTacaribe virusMachupo virusChapare virusmammarenavirusVero E6 cellsGuanarito virusLassa virusGP2 subunitJunín virusHartley guinea pigsInhibitorinhibitorinhibit

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