Structure of Letermovir
CAS No.: 917389-32-3
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Letermovir (AIC246) is a potent inhibitor of CMV that targets the viral terminase complex and remains effective against virus strains resistant to DNA polymerase inhibitors.
Synonyms: AIC246; MK-8228; Prevymis
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Mulder, Lance ; da Sá, Renata Vieira ; Korsten, Joep ; Freeze, Eline ; Schotting, Amber J ; Koen, Gerrit , et al.
Abstract: Human cytomegalovirus (CMV) infections can cause severe neurological complications, particularly in newborns and immunocompromised patients. Children affected with congenital CMV infection may develop long-term neurological damage and intellectual disabilities. Currently, postnatal antiviral therapies are limited and there are no prenatal options available. Research on antivirals against congenital CMV infections is, at least partly, restricted due to the lack of physiologically relevant models and the use of lab-adapted CMV strains with limited clinical relevance. In this study, we evaluated the toxicity and antiviral efficacy of three FDA-approved anti-CMV drugs against two CMV strains, a clinical and a lab-adapted strain, using two human induced pluripotent stem cell (iPSC-)derived central nervous system models, viz. neural progenitor cells (NPCs) and dorsal forebrain regionalized neural organoids (RNOs). We found iPSC line-dependent differences in antiviral toxicity. We observed that antiviral treatment restored NPCs and RNOs gene expression after CMV infection and reduced CMV copy numbers. Infection of NPCs and RNOs with the clinical CMV strain, but not with the lab-adapted strain, led to an impaired expression of cortical development markers. Our findings highlight the value of using physiologically relevant human models and clinical CMV strains to understand the neuropathogenesis of congenital CMV and to test therapeutic strategies.
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CAS No. : | 917389-32-3 |
Formula : | C29H28F4N4O4 |
M.W : | 572.55 |
SMILES Code : | FC1=C(N=C(N2CCN(C3=CC=CC(OC)=C3)CC2)N(C4=CC(C(F)(F)F)=CC=C4OC)[C@H]5CC(O)=O)C5=CC=C1 |
Synonyms : |
AIC246; MK-8228; Prevymis
|
MDL No. : | MFCD22572725 |
InChI Key : | FWYSMLBETOMXAG-QHCPKHFHSA-N |
Pubchem ID : | 45138674 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Clinical Trial:
NCT Number | Conditions | Phases | Recruitment | Completion Date | Locations |
NCT05362916 | People Living with HIV | ACTIVE_NOT_RECRUITING | 2025-12-31 | Mcgill University Health Cente... More >>r, Montreal, Quebec, H4A 3J1, Canada Less << | |
NCT06575374 | Cell Therapy | RECRUITING | 2027-08-01 | MD Anderson Cancer Center, Hou... More >>ston, Texas, 77030, United States Less << | |
NCT06449586 | Hematologic Malignancy | RECRUITING | 2026-06-01 | Tongji Hospital of Huazhong Un... More >>iversity of Science and Technology, Wuhan, Wuhan, Hubei, China|Ruijin Hospital of Shanghai Jiaotong University, Shanghai, Shanghai, China|The First Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China|Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China|Shanghai Liquan Hospital, Shanghai, China Less << | |
NCT05763823 | Cytomegalovirus Infection | PHASE3 | COMPLETED | 2024-04-18 | Anhui Provincial Hospital ( Si... More >>te 0024), Hefei, Anhui, 230071, China|Peking University First Hospital ( Site 0009), Beijing, Beijing, 100034, China|Peking University People's Hospital-Hematology ( Site 0033), Beijing, Beijing, 100034, China|The Second Affiliated Hospital of Third Military Medical University-Oncology Department ( Site 0002), Chongqing, Chongqing, 400037, China|Southwest Hospital of Third Military Medical University ( Site 0005), Chongqing, Chongqing, 400038, China|The Second Affiliated Hospital Chongqing Medical University ( Site 0013), Chongqing, Chongqing, 400072, China|Guangzhou First People's Hospital-Hematology Department ( Site 0001), Guangzhou, Guangdong, 510180, China|Southern Medical University Nanfang Hospital ( Site 0003), Guangzhou, Guangdong, 510515, China|Shenzhen Second People's Hospital-Hematology Department ( Site 0006), Shenzhen, Guangdong, 518035, China|Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 0028), Wuhan, Hubei, 430022, China|Tongji Hospital Tongji Medical,Science & Technology ( Site 0032), Wuhan, Hubei, 430030, China|The First Affiliated Hospital of Soochow University-hematology department ( Site 0029), Suzhou, Jiangsu, 215006, China|The Affiliated Hospital of Xuzhou Medical College ( Site 0022), Xuzhou, Jiangsu, 221006, China|The First affiliated hospital of Nanchang University (Xianghu campus) ( Site 0021), Nanchang, Jiangxi, 330209, China|The First Hospital of Jilin University-Hematology ( Site 0023), Changchun, Jilin, 130021, China|The 2nd Affiliated Hospital of Dalian Medical University ( Site 0019), Dalian, Liaoning, 116023, China|Shanghai General Hospital ( Site 0018), Shanghai, Shanghai, 200080, China|West China Hospital, Sichuan University ( Site 0008), Chengdu, Sichuan, 610041, China|The General Hospital of Western Theater Command ( Site 0007), Chengdu, Sichuan, 610083, China|Institute of hematology&blood disease hospital-Hematology ( Site 0030), Tianjin, Tianjin, 300020, China|The First Affiliated Hospital, Zhejiang University ( Site 0025), Hangzhou, Zhejiang, 310003, China Less << |
NCT06441669 | Cytomegalovirus Infection Reac... More >>tivation Less << | RECRUITING | 2026-05-20 | Anhui Provincial Hospital, Hef... More >>ei, Anhui, China Less << | |
NCT04732260 | Pregnant Women Undergoing TOP|... More >>TOP - Failed Attempted Termination of Pregnancy Less << | COMPLETED | 2021-11-12 | H?pital Necker - Enfants malad... More >>es, Paris, 75015, France Less << | |
NCT04904614 | Cytomegalovirus Disease|Cytome... More >>galovirus Infections|Heart Transplant Infection|Antiviral Toxicity|Neutropenia Less << | PHASE4 | ACTIVE_NOT_RECRUITING | 2025-12-30 | Tufts Medical Center, Boston, ... More >>Massachusetts, 02111, United States Less << |
NCT06118515 | Congenital Cytomegalovirus Inf... More >>ection Less << | PHASE1 | RECRUITING | 2025-08-31 | Children's of Alabama Child He... More >>alth Research Unit (CHRU), Birmingham, Alabama, 35233-0011, United States|Children's National Medical Center - Sheikh Zayed Campus - Infectious Disease, Washington, District of Columbia, 20010-2916, United States|Emory University School of Medicine, Atlanta, Georgia, 30322-1014, United States|University of Louisville School of Medicine - Norton Children's Hospital - Infectious Diseases, Louisville, Kentucky, 40202, United States|Louisiana State University Health Shreveport - Infectious Diseases, Shreveport, Louisiana, 71101, United States|University of Minnesota - Pediatric Infectious Disease, Minneapolis, Minnesota, 55454, United States|SUNY Upstate Medical University Hospital - Pediatrics, Syracuse, New York, 13210-2342, United States|Nationwide Children's Hospital - Neonatology - Center for Perinatal Research, Columbus, Ohio, 43205-2664, United States|University of Texas Southwestern Medical Center - Pediatrics, Dallas, Texas, 75390-9063, United States|Medical College of Wisconsin, Milwaukee, Wisconsin, 53226-3522, United States Less << |
NCT05656599 | CMV Infection|Hematopoietic St... More >>em Cell Transplantation Less << | ENROLLING_BY_INVITATION | 2025-12-25 | Department of Hematology, Peki... More >>ng University People's Hospital, Beijing, Beijing, 100044, China|People's Hospital of Peking University, Beijing, China Less << | |
NCT05914675 | The Incidence of Peripheral Bl... More >>ood CMV Activation and Confirmed Clinically Significant CMV Infection Within 24 Weeks After Transplantation Less << | PHASE4 | NOT_YET_RECRUITING | 2024-12-31 | - |
NCT06407232 | Cytomegalovirus Infections|Kid... More >>ney Transplant Infection|Pancreas Transplant Less << | PHASE3 | RECRUITING | 2025-09-26 | UW Hospital and Clinics, Madis... More >>on, Wisconsin, 53792, United States Less << |
NCT04312841 | B-Cell Prolymphocytic Leukemia... More >>|Chronic Lymphocytic Leukemia|Peripheral T-Cell Lymphoma|Primary Cutaneous T-Cell Non-Hodgkin Lymphoma|Sezary Syndrome|T-Cell Prolymphocytic Leukemia Less << | PHASE2 | ACTIVE_NOT_RECRUITING | 2024-12-31 | Ohio State University Comprehe... More >>nsive Cancer Center, Columbus, Ohio, 43210, United States Less << |
NCT05626530 | Cytomegalovirus Infections|Inf... More >>ection in Solid Organ Transplant Recipients|Neutropenia|Antiviral Toxicity Less << | PHASE4 | RECRUITING | 2025-12-15 | Tufts Medical Center-Division ... More >>of Geographic Medicine and Infectious Diseases, Boston, Massachusetts, 02111, United States Less << |
NCT06626555 | HIV | PHASE2 | NOT_YET_RECRUITING | 2025-03-26 | - |
NCT05789615 | CMV Infection|Hematopoietic St... More >>em Cell Transplantation Less << | RECRUITING | 2024-12-31 | The First Affiliated Hospital ... More >>of Soochow university, Suzhou, Jiangsu, China Less << | |
NCT06306989 | Letemovir for the Prevention o... More >>f CMV Infection After Allo-HSCT Less << | RECRUITING | 2025-12-01 | Cao, Weijie, Zhengzhou, Henan,... More >> 450000, China Less << | |
NCT05969743 | Graft-versus-host-disease|CMV | PHASE2 | NOT_YET_RECRUITING | 2025-07-31 | - |
NCT03728426 | Cytomegalovirus Infections | PHASE2 | COMPLETED | 2022-03-28 | Brigham and Women's Hospital, ... More >>Boston, Massachusetts, 02115, United States|Massachusetts General Hospital Cancer Center, Boston, Massachusetts, 02214, United States|Boston Children's Hospital, Boston, Massachusetts, 02215, United States|Dana-Farber Cancer Institute, Boston, Massachusetts, 02215, United States Less << |
Tags: Letermovir | AIC246 | MK-8228 | AIC 246 | AIC-246 | MK8228 | MK 8228 | MK-8228 | CMV | Cytomegalovirus | CMV inhibitor | viral terminase complex | antiviral agent | DNA polymerase resistance | HCMV inhibitor | 917389-32-3
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