half-life

Ceftriaxone sodium hydrate is a broad-spectrum cephalosporin antibiotic with a very long half-life and high penetrability to meninges, eyes and inner ears.

(R)-5-Oxopyrrolidine-2-carboxylic acid (D-Pyroglutamic acid) is a cyclic derivative of glutamic acid, physiologically present in mammalian tissues. It releases GABA from the cerebral cortex and exhibits anti-anxiety effects in a simple approach-avoidance conflict situation in rats. In clinical pharmacology experiments, it significantly shortens the plasma half-life of ethanol during acute intoxication.

Torsemide (AC-4464) is an anilinopyridine sulfonylurea belonging to the class of loop diuretics. Torsemide has a prolonged duration of action compared to other loop diuretics, is extensively protein bound in plasma and has a relatively long half-life.

Secnidazole (PM-185184) is a second-generation 5-nitroimidazole antimicrobial that is structurally related to other 5-nitroimidazoles including [DB00916] and [DB00911], but displays improved oral absorption and longer terminal elimination half-life than antimicrobial agents in this class [A27210]. Secnidazole is selective against many anaerobic Gram-positive and Gram-negative bacteria and protozoa.

PF-03635659 is a potent and long dissociative half-life muscarinic M3 antagonist (Ki: 0.2 nM) that shows potential for the treatment of chronic obstructive pulmonary disease (COPD).

KYL acetate is an EphA4 receptor tyrosine kinase inhibitor (Kd = 0.8 μM); inhibits EphA4-EphrinA5 interactions (IC50 = 6.34 μM). Prevents AβO induced synaptic damage, dendritic spine loss and prevents the blocking of LTP in hippocampal CA3-CA1 transmissions. Exhibits a long half life in cell culture media (8 and 12 hours in PC3 and C2C12 media respectively). Neuroprotective.

Minamestane is a novel irreversible aromatase inhibitor.Minamestane induces time-dependent inhibition of human placental aromatase with a half-life of 4 minutes and a K of 59 nM.Minamestane has antitumor activity.

GS-829845 is a JAK1 inhibitor, the main component of the active metabolite of Filgotinib, which is approximately 10-fold less potent and has a longer half-life than the parent.

Didesmethyl cariprazine, a metabolite of Cariprazine, is the major cyclic active part. Didesmethyl cariprazine has a long half-life of 1-3 weeks. Cariprazine is a potent D3 preference D3/D2 receptor partial agonist of dopamine for the treatment of schizophrenia, bipolar mania, and depression, with a high affinity for d3 and d2 receptors and a moderate affinity for 5-HT 1A receptors.

Exendin-4 (Exenatide) is a glucagon-like peptide-1 receptor (GLP-1) agonist (IC50: 3.22 nM). Exenatide is a 39 amino acid peptide. Compared to GLP-1, exenatide has a longer half-life of 2.4 hours.

Clevudine (Levovir) is a synthetic pyrimidine analogue with activity against hepatitis B virus (HBV). Intracellularly, clevudine is phosphorylated to its active metabolites, clevudine monophosphate and triphosphate. The triphosphate metabolite competes with thymidine for incorporation into viral DNA, thereby causing DNA chain termination and inhibiting the function of HBV DNA polymerase (reverse transcriptase). Clevudine has a long half-life and shows significant reduction of covalently closed circular DNA (cccDNA), therefore the patient is less likely to have a relapse after treatment is discontinued.

Fluorofenidone (AKF-PD) attenuates the progression of renal interstitial fibrosis partly by suppressing NADPH oxidase and extracellular matrix (ECM) deposition via the PI3K/Akt signalling pathway. Fluorofenidone is an analogue of AMR69. Which displays equivalent lower toxicity, antifibrotic activity, and longer half-life.

Aspoxicillin, a broad-spectrum antimicrobial agent, demonstrates efficacy against 68 isolates of Actinobacillus pleuropneumoniae, with a minimum inhibitory concentration (MIC90) of <= 0.05 μg/ml. It exhibits a prolonged half-life of 55 minutes in mouse serum.

Regadenoson (CVT-3146) is an adenosine derivative and selective A2A adenosine receptor agonist with coronary vasodilating activity. Upon administration, regadenoson selectively binds to and activates the A2A adenosine receptor, which induces coronary vasodilation. This leads to an increase in coronary blood flow and enhances myocardial perfusion. Compared to adenosine, regadenoson has a longer half-life and shows higher selectivity towards the A2A adenosine receptor. This agent is a very weak agonist for the A1 adenosine receptor and has negligible affinity for the A2B and A3 adenosine receptors.

Spirorenone is an androstadienone derivative as a highly effective aldosterone antagonist. Spirorenone is 8.6 times as potent as spironolactone, but showed a lower affinity for the mineralocorticoid receptors. In phase I clinical trials Spirorenone was absorbed with a half-life of 20-30 min, achieving maximum concentrations of about 100 ng/ml (10 mg) and 260 ng/ml (40 mg) after 1-2 h. Disposition of the parent drug was biphasic with half-lives of 50-60 min (distribution) and 5-6 h (elimination). Neither significant accumulation nor enzyme induction was observed after prolonged treatment.

Prostaglandin D2 (PGD2) is a primary enzymatic prostaglandin derived from PGH2 and is abundantly produced in the cerebrospinal fluid (CSF) by the lipocalin-type PGD synthase, and peripherally by myeloid cells such as mast cells and basophils via a hematopoietic-type PGD synthase. PGD2 is chemically unstable and presents challenges for use and analysis due to its brief in vivo half-life. Δ12-PGD2, an initial decomposition product of PGD2, acts as an intermediate in the pathway to Δ12-PGJ2, a cyclopentenone prostaglandin known for its antimitotic and carcinogenic properties. The metabolism of Δ12-PGD2 involves the addition of thiol nucleophiles, a common pathway for many cyclopentenone prostaglandins.

TG11-77 HCl is a novel, Potent, Selective, Water Soluble, Brain-Permeable EP2 Receptor Antagonist. TG11-77 HCl has a Schild KB of 9.7 nM on EP2, a water solubility of 2.5 mM, a brain-to-plasma ratio of 0.4, and a plasma half-life of 2.4 h in mice. TG11-77 HCl are representative second generation EP2 antagonists with improved pharmacodynamic and pharmacokinetic properties.

Bupranolol is a non-selective beta blocker without intrinsic sympathomimetic activity (ISA), but with strong membrane stabilizing activity. Its potency is similar to propranolol. Bupranolol is quickly and completely absorbed from the gut. Over 90% undergo first-pass metabolism. Bupranolol has a plasma half life of about two to four hours, with levels never reaching 1 µg/l in therapeutic doses. The main metabolite is carboxybupranolol, 4-chloro-3-[3-(1,1-dimethylethylamino)-2-hydroxy-propyloxy]benzoic acid – that is, the methyl group at the benzene ring is oxidized to a carboxyl group –, of which 88% are eliminated renally within 24 hours.

Etozolin HCl is a safe and effective diuretic agent in the treatment of acute cardiac failure. In isolated rings of guinea-pig aorta not responding to acetylcholine, the diuretic dexetozoline did not influence basal vascular tone but inhibited noradrenaline- and histamine-induced contractions. Dexetozoline has a very high bioavailability after oral administration and is fairly lipohilic. The half-life of etozolin is 2.5 h. Dexetozoline accumulates in cirrhosis.

(±)-4-hydroxy Propranolol β-D-glucuronide is a metabolite of (±)-4-hydroxy propranolol , which is a metabolite of propranolol. The apparent half-life of (±)-4-hydroxy propranolol β-D-glucuronide is similar to propranolol and 4-hydroxy propranolol. Propranolol is a β-adrenergic antagonist, and the active enantiomer, (S)-(-)-propranolol , has log Kd values of -8.16, -9.08, and -6.93 for β1, β2, and β3, respectively.

TG11-77 free base is a novel, Potent, Selective, Water Soluble, Brain-Permeable EP2 Receptor Antagonist. TG11-77 free base has a Schild KB of 9.7 nM on EP2, a water solubility of 2.5 mM, a brain-to-plasma ratio of 0.4, and a plasma half-life of 2.4 h in mice. TG11-77 free base are representative second generation EP2 antagonists with improved pharmacodynamic and pharmacokinetic properties.

SD-254 is a deuterium analog of Effexor, with fewer side effects and a longer half-life.

S-Nitrosothiols (RSNOs) are a class of molecules that function as exogenous and endogenous nitric oxide (NO) donors. RSNOs found in vivo include proteins such as S-nitrosohemoglobin and S-nitrosoalbumin, as well as low molecular weight species such as S-nitrosoglutathione (GSNO) and S-nitrosocysteine (CysNO). CAY10565 is a member of a new class of S-nitrosothiol species that act as NO donors under acidic conditions. It decomposes with a half-life of 130 minutes in 0.1 M phosphate buffer, pH 5.0, at 37°C and relaxes phenylephrine-constricted rat aortic strips 71% and 44% at pH 6.0 and 7.4, respectively.

OPC-167832 is a potent and orally active dprE1 Inhibitor with an IC50 of 0.258 μM. OPC-167832 has antituberculosis activity and can be used for the research of tuberculosis caused by Mycobacterium tuberculosis[1]. OPC-167832 exhibits very low MICs against laboratory strains of M. tuberculosis H37Rv (MIC: 0.0005 μg/ml) and Kurono (MIC: 0.0005 μg/ml) and strains with monoresistance to rifampin (RIF), isoniazid (INH), ethambutol (EMB), streptomycin (STR), and pyrazinamide (PZA) (MIC: 0.00024-0.001 μg/ml). However, OPC-167832 has minimal or no activity against standard strains of nonmycobacterial aerobic and anaerobic bacteria[1].The IC90 values of OPC-167832 against intracellular M. tuberculosis strains H37Rv and Kurono are 0.0048 and 0.0027 μg/ml, respectively. OPC-167832 shows bactericidal activity against intracellular M. tuberculosis at a low concentration, and the bactericidal activity is saturated at concentrations of 0.004 μg/ml or higher[1]. OPC-167832 (oral administration; 0.625-10 mg/kg) exhibits a good pharmacokinetic characteristic. The plasma reaches peak at 0.5 h to 1.0 h (tmax) and is eliminated with a half-life (t1/2) of 1.3 h to 2.1 h OPC-167832 distribution in the lungs is approximately 2 times higher than that in plasma, and the Cmax and AUCt of OPC-167832 in plasma and the lungs shows dose dependency[1].OPC-167832 (oral administration; 0.625-10 mg/kg; 4 weeks) significantly reduces lung CFU compared to the vehicle group. The dose-dependent decrease of lung CFU is observed from 0.625 mg/kg to 2.5 mg/kg. In a M. tuberculosis Kurono-infected ICR female mice model. OPC-167832 combines with DMD, BDQ, or LVX via oral gavage exhibits significantly higher efficacies than each single agent alone[1].[1].OPC-167832 (oral gavage; 2.5 mg/kg; combination with DCMB; 12 weeks) demonstrates the most potent efficacy when compares with DC, DCB. The lung CFU count after 6 weeks of treatment is below the detection limit, and at the end of just 8 weeks of treatment, the bacteria in the lungs of all the evaluated mice had already been eradicate[1]. [1]. Norimitsu Hariguchi, et al. OPC-167832, a Novel Carbostyril Derivative with Potent Antituberculosis Activity as a DprE1 Inhibitor.Antimicrob Agents Chemother. 2020 May 21;64(6):e02020-19.

MeOIstPyrd is an anti-skin cancer agent that inhibits cell proliferation, migration, and spheroid formation by activating the mitochondrial intrinsic apoptotic pathway. It induces DNA damage, activates p53, increases its half-life, and stabilizes p53 via ser15 phosphorylation. Additionally, MeOIstPyrd interfaces with MDM2 within the p53 sub-pocket, preventing the p53-MDM2 interaction [1].

Angeli’s salt is regarded as a classical nitroxyl (NO-) donor, but under certain conditions evolution of NO is also observed.1 It spontaneously dissociates in a pH-dependent, first-order process with a half-life of 2.3 minutes at 37°C (pH 7.4) to liberate 0.54 moles of NO per mole of parent compound.[1],[2]

BIO5192 hydrate is a selective and potent integrin α4β1 (VLA-4) inhibitor (Kd < 10 pM). The compound selectively binds to α4β1 (IC50 = 1.8 nM) over various other integrins and results in a 30-fold increase in mobilization of murine hematopoietic stem and progenitors (HSPCs) over basal levels[1][2].

9-deoxy-9-methylene-16,16-dimethyl Prostaglandin E2 (Meteneprost) is a potent analog of prostaglandin E2 with an extended half-life in vivo. In combination with various other prostaglandin derivatives, it results in the termination of first trimester pregnancy in monkeys. A single intramuscular injection containing 0.5 mg of meteneprost and 7.5 mg of 17-phenyl trinor PGF1α is very effective in terminating early pregnancy. This prostaglandin mixture is ineffective on monkeys in their third trimester of pregnancy. Meteneprost, when compared to PGE2 and PGF1α, in monkey and rat, does not result in unwanted side effects such as fever or gastrointestinal problems.

NOD1/2 Antagonist-1 is a potent dual inhibitor of nucleotide-binding oligomerization domain-like receptors 1 and 2 (NOD1/2), displaying inhibitory concentrations (IC50) of 1.13 μM for NOD1 and 0.77 μM for NOD2. It exhibits an acceptable half-life (T1/2) of 67.6 minutes. Additionally, NOD1/2 Antagonist-1 enhances the antitumor efficiency of Paclitaxel (PTX).

Pavurutamab (AMG-701) is a bispecific T-cell engager targeting CD3 and B-cell maturation antigens (BCMA), with an extended half-life derived from Pacanalotamab. Its Fc region is engineered for improved pharmacokinetics, offering potential in immune regulation and treatment of multiple myeloma (MM) [1] [2] [3] [4].

Taccalonolide AJ is a microtubule stabilizer; it has excellent and highly persistent antitumor efficacy when administered directly to the tumor, suggesting that the lack of antitumor efficacy seen with systemic administration of AJ is likely due to its sh

KYL peptide is an EphA4 receptor tyrosine kinase inhibitor (Kd = 0.8 μM); inhibits EphA4-EphrinA5 interactions (IC50 = 6.34 μM). Prevents AβO induced synaptic damage, dendritic spine loss and prevents the blocking of LTP in hippocampal CA3-CA1 transmissions. Exhibits a long half life in cell culture media (8 and 12 hours in PC3 and C2C12 media respectively). Neuroprotective.

(+)-Cevimeline hydrochloride hemihydrate ((+)-SNI-2011), a potent muscarinic receptor agonist, shows promise as a therapeutic candidate for xerostomia in Sjogren's syndrome. It exhibits a broad pharmacological profile across various systems in animal models including mice, rats, guinea pigs, rabbits, and dogs. Metabolism studies using rat and dog liver microsomes reveal rapid absorption with peak plasma concentrations (Cmax) within one hour post-oral administration and a half-life (t1 2) between 0.4 to 1.1 hours. Bioavailability is 50% in rats and 30% in dogs. Metabolic analysis shows species-specific differences: rats produce S- and N-oxidized metabolites, while dogs produce only N-oxidized metabolites. Sex-based pharmacokinetic differences were noted in rats but not in dogs. In vitro studies indicate cytochrome P450 (CYP) and flavin-containing monooxygenase (FMO) involvement in the sulfoxidation and N-oxidation of SNI-2011, with CYP2D and CYP3A mainly responsible for sulfoxidation in rat liver microsomes.

PGI3 is synthesized from EPA by COX and PGI synthase. PGI3 has a short in vivo half-life and is hydrolyzed to δ17-6-keto PGF1α. The platelet and vascular activity of PGI3 is equivalent to that of PGI2.

SARS-CoV-2-IN-14 is a potent and oral inhibitor of SARS-CoV-2 (IC50:0.39 μM), which is an analogue of niclosamide. SARS-CoV-2-IN-14 was more stable than niclosamide in the determination of human plasma and liver S9 enzyme. Oral administration of SARS-CoV-2-IN-14 can improve its bioavailability and half-life.

Dasiglucagon acetate is a novel glucagon analog for diabetic hypoglycemia therapy. Dasiglucagon acetate has demonstrated established solubility and stability in an aqueous formulation. Pharmacokinetics studies have shown dasiglucagon acetate to exhibit hi

WAY-639872 is an active molecule exhibiting (in vivo) efficacy. This compound selectively targets (enzyme X), demonstrating inhibition with an IC50 of 2 nM. Importantly, it possesses a (high level) of specificity, showing minimal interaction with related enzymes. WAY-639872 maintains stability (under physiological pH), and its pharmacokinetic profile indicates an (excellent oral bioavailability) of 90%. Furthermore, the molecule remains unmetabolized for an extended period, with a half-life exceeding 24 hours. Its safety profile reveals no significant (adverse effects), and it has successfully completed Phase I clinical trials.

Antimalarial agent 33 (compound 5g) exhibits antiplasmodial activity targeting both erythrocytic and hepatic stages of Plasmodium, with an effective concentration (EC50) of 1.1 μM against the K1 strain of P. falciparum. It demonstrates improved microsomal stability with a half-life (T1 2) of 29 minutes and displays no significant cytotoxicity against primary hepatocytes [1].

Gresonitamab (AMG 910), a half-life extended (HLE) bispecific T-cell engager (BiTE) antibody, specifically targets CD3-positive T cells and CLDN18.2-expressing tumor cells, offering potential research applications in adenocarcinoma [1].

Efruxifermin, an Fc-FGF21 fusion protein consisting of a human IgG1 Fc domain linked to modified human FGF21, exhibits a prolonged half-life and enhanced receptor affinity compared to its native counterpart. It is utilized in researching non-alcoholic steatohepatitis [1].

S1P1 agonist 4 exhibits enhanced potency with an EC 50 value of less than 0.05 mg/kg and a predicted human half-life (t1/2) of approximately 5 days, indicating a favorable pharmacological profile.

Delimotecan is a DNA topoisomerase I inhibitor. Delimotecan had a long terminal half-life of 109 h, and relatively high exposures to T-2513 and SN-38 were obtained. The percentage decrease in WBC and absolute neutrophil count significantly correlated with

SNJ-1945 is a calpain inhibitor with more favorable retinal penetration, high oral bioavailability, and long half-life. SNJ1945 rescued defective function in lissencephaly. SNJ-1945 protects SH-SY5Y cells against MPP(+) and rotenone. SNJ-1945 reduces murine retinal cell death in vitro and in vivo. SNJ-1945 has good aqueous solubility, can prevents the heart from KCl arrest-reperfusion injury associated with the impairment of total Ca(2+) handling by inhibiting the proteolysis of alpha-fodrin as a cardioplegia.

Prostacyclin (PGI2) is a cyclooxygenase metabolite with antithrombotic properties found in vascular endothelial cells. The half-life is short both in vivo and in vitro, ranging from 30 seconds to a few minutes. CG 4305 is a stable carbacyclic analog of PGI2 that inhibits ADP-induced platelet aggregation 25% at a concentration of 50 nM. Doses of 10 mg/kg (oral) or 1 mg/kg (intraduodenal) have been shown to prevent rabbit carotid artery thrombosis.

S-Nitrosothiols (RSNOs) are a class of molecules that function as exogenous and endogenous nitric oxide (NO) donors. RSNOs found in vivo include proteins such as S-nitrosohemoglobin and S-nitrosoalbumin, as well as low molecular weight species such as S-nitrosoglutathione (GSNO) and S-nitrosocysteine (CysNO). CAY10563 is a member of a new class of S-nitrosothiol species that act as an NO donors under acidic conditions. It decomposes with a half-life of one minute in 0.1 M phosphate buffer, pH 5.0, at 37°C and relaxes phenylephrine-constricted rat aortic strips 59% and 16% at pH 6.0 and 7.4, respectively.

16,16-dimethyl PGA2 is a metabolism-resistant analog of PGA2 with a prolonged in vivo half-life. It inhibits the proliferation of Sendai virus in cultured African green monkey kidney cells by >90% at a concentration of 4 μg/ml. Daily infusion of 10 μg of 16,16-dimethyl PGA2 methyl ester into mice infected with influenza A virus increased survival by 40%. Similar treatment of mice inoculated with erythroleukemia cells delayed tumor growth and increased survival time.

OX2R-IN-1 is an OX2R antagonist (a potential OX2R binding agent) that exhibits low cytotoxicity (IC50: 484 μM). oX2R-IN-1 has blood-brain barrier permeability and a short drug half-life.

Sotrovimab (VIR 7831), a human IgG1κ pan-sarbecovirus monoclonal antibody (mAb), effectively neutralizes SARS-CoV-2, SARS-CoV-1, and various other sarbecoviruses. Developed from S309, it possesses a prolonged half-life and excellent bioavailability within the respiratory mucosa. Its mechanism potentially facilitates immune-mediated viral elimination, thereby averting the advancement of Covid-19 during the disease's early stages [1][2].

Phosphoramide mustard cyclohexanamine is the major metabolite for Cyclophosphamide , with anticancer activitiy. Phosphoramide mustard cyclohexanamine induces DNA adduct formation in ovarian granulosa cells, induces DNA damage and elicits the ovarian DNA repair response[1][2]. Phosphoramide mustard cyclohexanamine causes cytotoxicity through forming cross-linked DNA adducts which inhibit DNA strand separation during replication[1].Phosphoramide mustard cyclohexanamine destroys rapidly dividing cells by forming NOR-G-OH, NOR-G and G-NOR-G adducts with DNA, potentially leading to DNA damage[1].Phosphoramide mustard cyclohexanamine (3-6 μM; 48 hours) reduces cell viability in rat spontaneously immortalized granulosa cells (SIGCs)[1].Phosphoramide mustard cyclohexanamine (3-6 μM; 24-48 hours) induces DNA adduct formation[1].Phosphoramide mustard cyclohexanamine (3-6 μM; 24-48 hours) induces ovarian DNA damage in rat ovaries[1].Phosphoramide mustard cyclohexanamine increases DNA damage responses (DDR) gene (Atm, Parp1, Prkdc, Xrcc6, Brca1, Rad51) mRNA expression level[1].Phosphoramide mustard cyclohexanamine (3-6 μM; 24-48 hours) increased DDR proteins[1]. Cell Viability Assay[1] Cell Line: SIGCs Phosphoramide mustard cyclohexanamine (2.1-20.7 mg kg; i.p.; daily; for 5 days) inhibits subcutaneous tumor growth in rats[2].Phosphoramide mustard cyclohexanamine (86.0 mg kg; i.v.) has a plasma disappearance half-life of 15.1 minutes[2]. Animal Model: Rat, subcutaneously implanted Walker 256 carcinosarcoma tumor[2] [1]. Shanthi Ganesan, et al. Phosphoramide mustard exposure induces DNA adduct formation and the DNA damage repair response in rat ovarian granulosa cells. Toxicol Appl Pharmacol. 2015 Feb 1; 282(3): 252-258. [2]. S Genka, et al. Brain and plasma pharmacokinetics and anticancer activities of cyclophosphamide and phosphoramide mustard in the rat. Cancer Chemother Pharmacol. 1990;27(1):1-7.

Methylcarbamyl PAF C-16 is a stable analog of PAF C-16 with a half-life greater than 100 minutes in platelet poor plasma due to its resistance to degradation by PAF-AH. It is nearly equipotent with PAF C-16 in its ability to induce platelet aggregation both in isolated platelets and in platelet-rich plasma. In NRK-49 cells overexpressing the PAF receptor, both PAF C-16 and methylcarbamyl PAF C-16 cause the induction of c-myc and c-fos and the activation of mitogen-activated protein kinase. Methylcarbamyl PAF C-16 induces G1 phase cell cycle arrest, suggesting a potential role for PAF in the inhibition of oncogenic transformation.