Letermovir

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Cat Number

API917389323

CAS Number

917389-32-3

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CAS Number

917389-32-3

EINECS

805-689-9

Storage

Store at room temperature

Synonyms

Prevymis; AIC246; MK-8228; 1H09Y5WO1F

Molecular Formula

C29H28F4N4O4

Molecular Weight

572.5

Smiles

COC1=C(C=C(C=C1)C(F)(F)F)N2[C@H](C3=C(C(=CC=C3)F)N=C2N4CCN(CC4)C5=CC(=CC=C5)OC)CC(=O)O

Appearance

Solid powder

Boiling Point

706.5±70.0°C (Predicted)

Relative Density

1.37±0.1 (Predicted)

General Description

Letermovir is a novel, small‑molecule antiviral agent with a unique chemical structure, characterized by a quinazoline core and a piperazine ring. It is specifically designed to inhibit the viral terminase complex of cytomegalovirus (CMV), distinguishing it from all other anti‑CMV drugs which target the viral DNA polymerase.

Mechanism of Action

Letermovir targets the CMV terminase complex, specifically the pUL51, pUL56, and pUL89 subunits, preventing the cleavage and packaging of viral DNA into capsids. By inhibiting this essential late‑stage step in viral replication, the drug blocks the formation of infectious virions without interfering with viral DNA synthesis or host cell polymerases. The binding is non‑competitive and specific to CMV.

Application

Letermovir is indicated for the prophylaxis of CMV reactivation and disease in adult CMV‑seropositive recipients of allogeneic hematopoietic stem cell transplantation (HSCT). It is also used for the treatment of CMV infection in patients refractory or resistant to standard therapies. The drug has a favorable safety profile, with minimal myelosuppression or nephrotoxicity compared to ganciclovir.

In 64 CMV-seropositive patients undergoing HLA-mismatched allo-HCT with post-transplant cyclophosphamide, letermovir prophylaxis reduced the 180-day incidence of CMV infection requiring therapy from 68.8% to 21.9% (HR 0.19, 95% CI 0.08–0.47, P<0.001). Persistent CMV infection (>28 days therapy) was more common without letermovir (31.2% vs 6.2%).

Fig. 1 Cumulative incidence of treatment-related mortality (A) and Kaplan-Meier estimates of overall survival (B) in subjects. (Lin A, et al., 2021)

References

Lin A, et al. Letermovir for Prevention of Cytomegalovirus Reactivation in Haploidentical and Mismatched Adult Donor Allogeneic Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide for Graft-versus-Host Disease Prophylaxis. Transplant Cell Ther. 2021;27(1):85.e1-85.e6.

In a prospective cohort of allogeneic HCT recipients, letermovir prophylaxis was associated with decreased polyfunctional CMV‑specific T‑cell responses (to IE‑1 and pp65) at 3 months compared to controls receiving preemptive therapy, even after adjustment for donor serostatus, lymphocyte count, and steroid use. Among letermovir recipients, greater CMV DNAemia correlated with stronger CD8+ responses. Letermovir may delay CMV‑specific immune reconstitution due to reduced antigen exposure.

Fig. 2 Multivariable linear regression of CMV kinetics with polyfunctional CMV-specific T-cell immunity in letermovir recipients only. (Zamora D, et al., 2021)

References

Zamora D, et al. Cytomegalovirus-specific T-cell reconstitution following letermovir prophylaxis after hematopoietic cell transplantation. Blood. 2021;138(1):34-43.

Does Letermovir require protection from light during long-term storage?

Yes, it is photosensitive. UV exposure can cause photodegradation and discoloration. Store in light-resistant containers, preferably original opaque packaging.

What is the recommended storage temperature for Letermovir?

Store at controlled room temperature (15-25°C). Avoid temperatures above 30°C, which can soften the powder and accelerate oxidative degradation.

Is Letermovir hygroscopic, and how is this managed?

It is slightly hygroscopic. Under high humidity (>70% RH), it may absorb moisture and clump. Storage in tightly sealed containers with desiccant is recommended.

How is the impurity letermovir N-oxide (an oxidative degradation product) monitored?

This degradation product is quantified using a stability-indicating HPLC method, ensuring it remains within ICH qualification thresholds.