Valganciclovir-d5 (TFA) is the deuterium labeled Valganciclovir TFA[1]. Valganciclovir, the L-valyl ester of ganciclovir, is actually a prodrug for ganciclovir. Valganciclovir is an antiviral medication used to treat cytomegalovirus infections[2][3][4].
Ganciclovir (INN) is an antiviral medication used to treat or prevent cytomegalovirus (CMV) infections. Ganciclovir is a synthetic analogue of 2′-deoxy-guanosine. It is first phosphorylated to ganciclovir monophosphate by a viral kinase encoded by the cytomegalovirus (CMV) gene UL97 during infection. Subsequently, cellular kinases catalyze the formation of ganciclovir diphosphate and ganciclovir triphosphate, which is present in 10-fold greater concentrations in CMV or herpes simplex virus (HSV)-infected cells than uninfected cells. A prodrug form with improved oral bioavailability (valganciclovir) has also been developed.
Valganciclovir-d8 (hydrochloride) is the deuterium labeled Valganciclovir hydrochloride[1]. Valganciclovir hydrochloride, the L-valyl ester of ganciclovir, is actually a prodrug for ganciclovir[2][3][4].
Valganciclovir (hydrochloride), the L-valyl ester of ganciclovir, is actually a prodrug for ganciclovir. Valganciclovir is an antiviral medication used to treat cytomegalovirus infections.IC50 Value: Target: CMVin vitro: In cell culture model systems using Caco-2 cells for PEPT1 and SKPT cells for PEPT2, valganciclovir inhibited glycylsarcosine transport mediated by PEPT1 and PEPT2 with K(i) values (inhibition constant) of 1.68+/-0.30 and 0.043+/- 0.005 mM, respectively. The inhibition by valganciclovir was competitive in both cases [1].in vivo: 37 patients were enrolled; 19 patients received treatment with VGV and 18 patients received treatment with GCV. The VGV was not inferior in efficacy to GCV as pre-emptive therapy, with rates of viral clearance at 28 days of 89.5% and 83%, respectively (P-value for non-inferiority = 0.030). Toxicities were similar between the 2 arms. No patients developed CMV disease [2]. Patients being treated with an alemtuzumab-containing regimen received prophylaxis with either valaciclovir 500 mg orally daily orvalganciclovir 450 mg orally twice daily. None of the 20 patients randomized to valganciclovir experienced CMV reactivation (P = .004) [3].
Regavirumab (MCA C23) is a human monoclonal antibody against cytomegalovirus (CMV), human serum albumin (HSA) and amino acetic acid[1].
FIT-039 is a selective, ATP-competitive and orally active CDK9 inhibitor with an IC50 of 5.8 μM for CKD9/cyclin T1. FIT-039 does not inhibit other CDKs and other kinases. FIT-039 inhibits replication of HSV-1 (IC50 of 0.69 μM), HSV-2, human adenovirus, and human CMV. FIT-039 is a promising antiviral agent for inhibiting drug-resistant HSVs and other DNA viruses.
Braco-19 is a potent telomerase/telomere inhibitor, preventing the capping and catalytic action of telomerase. Braco-19 acts as G-quadruplex (GQ) binding ligand, stabilizing G-quadruplexes formation at the 3V telomeric DNA overhang and produce rapid senescence or selective cell death. Braco-19 is also a HAdV virus replication inhibitor[1][2].
Cidofovir dehydrate is an injectable antiviral medication for the treatment of cytomegalovirus (CMV) retinitis, which suppresses virus replication by selective inhibition of viral DNA synthesis.Target: CMV DNA polymeraseCidofovir is an injectable antiviral medication for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. It suppresses CMV replication by selective inhibition of viral DNA polymerase and therefore prevention of viral replication and transcription. It is an acyclic nucleoside phosphonate, and is therefore independent of phosphorylation by viral enzymes, unlike acyclovir.Cidofovir was discovered at the Institute of Organic Chemistry and Biochemistry, Prague, by Antonín Hol?, and developed by Gilead Sciences and is marketed with the brand name Vistide by Gilead in the USA, and by Pfizer elsewhere. Maintenance therapy with cidofovir involves an infusion only once every two weeks, making it a convenient treatment option. Because dosing is relatively infrequent, a permanent catheter is not necessary for infusions.
Maribavir is a potent inhibitor of histone phosphorylation catalyzed by wild-type pUL97 in vitro, with an IC50 of 3 nM. Maribavir has potent antiviral activity against HCMV and Epstein-Barr virus (EBV).
Cyclic HPMPC is a potent antiviral agent. Cyclic HPMPC can increase arterial oxygen saturation levels in lethal vaccinia virus (IHD strain)-infected mice. Cyclic HPMPC improves the outcome of congenital guinea pig cytomegalovirus (GPCMV) infection and decreases viral replication in guinea pig model[1][2].
Ganciclovir (BW 759) sodium, a nucleoside analogue and an orally active antiviral agent, shows activity against CMV. Ganciclovir sodium also has activity in vitro against members of the herpes group and some other DNA viruses. Ganciclovir sodium inhibits the in vitro replication of human herpes viruses (HSV 1 and 2, CMV) and adenovirus serotypes 1, 2, 4, 6, 8, 10, 19, 22 and 28. Ganciclovir sodium has an IC50 of 5.2 μM for feline herpesvirus type-1 (FHV-1)[1][2][3].
Triacetyl-ganciclovir is a Ganciclovir derivative. Ganciclovir is an orally active antiviral agent with activity against cytomegalovirus (CMV)[1].
Calcium trinatrium diethylenetriaminepentaacetic acid hydrate (Ca-DTPA trisodium salt hydrate) is a metal chelator and a useful antidote (such as acute cadmium intoxication). Diethylenetriaminepentaacetic acid calcium trisodium salt hydrate is a nontoxic inhibitor of CMV replication[1][2].
Tricin is a natural flavonoid present in large amounts in rice bran. Tricin can inhibit human cytomegalovirus (HCMV) replication by inhibiting CDK9. Tricin inhibits the proliferation and invasion of C6 glioma cells via the upregulation of focal-adhesion-finase (FAK)-targeting microRNA-7[1][2][3].
Brivudine is a thymidine analogue with antiviral activity, indicated for the early treatment of acute herpes zoster.
Bisindolylmaleimide IV (Arcyriarubin A) is a potent protein kinase C (PKC) inhibitor, with IC50s ranging from 0.1 to 0.55 μM. Bisindolylmaleimide IV also inhibits PKA (IC50=3.1-11.8μM)[1]. Bisindolylmaleimide IV is a potent, selective inhibitor of human cytomegalovirus (HCMV) replication in cell culture with an IC50 of 0.2 μM[2].
pUL89 Endonuclease-IN-2 (Compound 15k) is a potent inhibitor of human cytomegalovirus (HCMV) pUL89 endonuclease with the IC50 of 3.0 μM. Antiviral activities[1].
pUL89 Endonuclease-IN-1 (Compound 13d) is a potent inhibitor of human cytomegalovirus (HCMV) pUL89 endonuclease with the IC50 value of 0.88 μM and has antiviral activitiy[1].
SIRT1-IN-1 is a selective SIRT1 inhibitor with an IC50 of 0.205 μM. SIRT1-IN-1 inhibits SIRT2 with an IC50 of 11.5 μM[1]. SIRT1-IN-1, a indole, is a cytomegalovirus (CMV) inhibitors and has antiviral activity[2].
Fomivirsen (ISIS-2922 free base) is an antisense 21 mer phosphorothioate oligonucleotide. Fomivirsen is an antiviral agent that is used cytomegalovirus retinitis (CMV) research, incluiding in AIDs. Fomivirsen binds to and degrades the mRNAs encoding CMV immediate-early 2 protein, thus inhibiting virus proliferation[1][2].
PMEDAP is a potent inhibitor of human immunodeficiency virus (HIV) replication. PMEDAP has anti-murine cytomegalovirus (MCMV) activity. PMEDAP is a very potent inhibitor of Moloney murine sarcoma virus (MSV)-induced tumor formation and associated mortality[1][2].
SB-734117 is a human cytomegalovirus (HCMV) replication inhibitor that prevents CREB and histone H3 post-translational modifications[1].
Cyclopropavir (Filociclovir; ZSM-I-62; MBX-400) is a broad-spectrum anti-herpesvirus compound, has good antiviral activity against cytomegalovirus (CMV), herpes simplex virus (HHV)-6 and HHV-8 with EC50s of 0.7 μM to 8 μM[1].
Cidofovir is an anti-CMV drug which can suppress CMV replication by selective inhibition of viral DNA polymerase and therefore prevention of viral replication and transcription.IC50 Value:Target: CMV DNA polymerasein vitro: The minimum concentrations of (S)-HPMPC required to inhibit CMV plaque formation by 50% was microgram/ml. The selectivity indices of (S)-HPMPC, as determined by the ratio of the 50% inhibitory concentration for cell growth to the 50% inhibitory concentration for plaque formation for CMV (AD-169 strain), was 1,500 [1]. The time course of uptake of HPMPC into Vero cells was linear between 10 and 75 min and proportional to the concentration in the medium from 10(-6) to 10(-2) M. HPMPC uptake was temperature sensitive and the rate of uptake was considerably lower at 27 degrees than at 37 degrees and almost totally inhibited at 4 degrees [2]. in vivo: Levels of cidofovirin serum following intravenous infusion were dose proportional over the dose range of 1.0 to 10.0 mg/kg of body weight and declined biexponentially with an overall mean +/- standard deviation terminal half-life of 2.6 +/- 1.2 h (n = 25). Approximately 90% of the intravenous dose was recovered unchanged in the urine in 24 h. The overall mean +/- standard deviation total clearance of the drug from serum (148 +/- 25 ml/h/kg; n = 25) approximated renal clearance (129 +/- 42 ml/h/kg; n = 25), which was significantly higher (P < 0.001) than the baseline creatinine clearance in the same patients (83 +/- 21 ml/h/kg; n = 12) [3]. Positive CMV urine cultures reverted to negative in 2 of 8 patients receiving doses of < or = 1.5 mg/kg twice weekly and 11 of 13 patients receiving higher doses. Cidofovir has in vivo anti-CMV activity demonstrated by prolonged clearing of CMV viruria, although this observation is tempered by the fact that clearance of viremia could not be demonstrated [4].Toxicity: Patients receiving 0.5 or 1.5 mg/kg twice weekly experienced no serious toxicity. The first two patients who received 5 mg/kg twice weekly developed glycosuria and 2+ proteinuria. Subsequent patients received concomitant probenecid to attempt to ameliorate renal toxicity [4].Clinical trial: FDA approved drug
Fiztasovimab (NPC-21; EV2038) is a fully human IgG1λ mAb against human cytomegalovirus (hCMV). Fiztasovimab acts neutralizing activity by binding to the antigenic domain 1 of glycoprotein B on hCMV envelope. Fiztasovimab inhibits cell-to-cell transmission of hCMV[1].
BRACO-19 is a potent small molecule Telomerase inhibitor (IC50=115 nM) that inhibits expression of human telomerase reverse transcriptase (hTERT); induces cellular senescence and inhibits growth of uterine cancer cells in vitro, inhibits growth of uterine tumor xenografts in vivo.
Soyasaponin II is a saponin with antiviral activity. Soyasaponin II inhibits the replication of HSV-1, HCMV, influenza virus, and HIV-1. Soyasaponin II shows potent inhibition on HSV-1 replication. Soyasaponin II serves as a inhibitor for YB-1 phosphorylation and NLRP3 inflammasome priming and could protect mice against LPS/GalN induced acute liver failure[1][2].
B220 is an antiviral agent which can inhibit the growth of HSV-1, HSV-2 and human cytomegalovirus (CMV).
Sevirumab (MSL-109) is a human IgG1 neutralizing monoclonal antibody against cytomegalovirus (CMV). Sevirumab recognizes CMV gH complexes and inhibits CMV replication with an EC50 of 0.3 μg/mL[1][2].
Fomivirsen sodium is an antisense 21 mer phosphorothioate oligonucleotide. Fomivirsen is an antiviral agent that is used cytomegalovirus retinitis (CMV) research, incluiding in AIDs. Fomivirsen sodium binds to and degrades the mRNAs encoding CMV immediate-early 2 protein (required for viral replication), thus providing bioactive effects for CMV retinitis by inhibition of virus proliferation[1].