| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| Other Sizes |
|
Purity: ≥98%
Morphothiadin (formerly GLS-4; GLS4) is a novel, potent and selective inhibitor of HBV replication, effective against both wild-type and adefovir-resistant HBV with an IC50 of 12 nM. Morphothiadin demonstrated potent inhibitory activities in HBV HepG2.2.15 cell assay with an EC50 value of 1nM, and it also exhibited high potency against various drug-resistant HBV viral strains with EC50 values in the range of 10-20nM, more potent than the typical HBV polymerase inhibitors such as lamivudine, telbivudine, and entecavir. Pharmacokinetic profiles of GLS4 were favorable and safety evaluation including acute toxicity and repeated toxicity study indicated that GLS4 was safe enough to support clinical experiments in human.
| Targets |
HBV(IC50= 12 nM )
|
|---|---|
| ln Vitro |
With an IC50 of 12 nM, morphothiadin is a strong inhibitor of both adefovir-resistant and wild-type HBV replication. Up to 25 μM, morphothiadin (GLS4) exhibits no toxicity. For primary hepatocytes, the cytotoxic dose (CC50) at which 50% of cells die is 115 μM for morphothiadin (P<0.001). In HepAD38 cells, the CC90 for morphothiadin is 190 μM (P<0.01). At 25 nM to 100 nM, phothiadin significantly reduces the amount of virus that accumulates in the supernatant of HepAD38 cells (P<0.02). The core protein in cells treated with morphothiadin decreases in a concentration-dependent manner, according to the results[2].
|
| ln Vivo |
Morphothiadin (GLS4) has an area under the concentration-time curve (AUC0-24) of 556 h•ng/mL from 0 to 24 hours. Following the intravenous injection of 10 mg/kg of morphothiadin, the apparent volume distribution and total plasma clearance are 7.38 liters/kg and 4.2 liters/h/kg, respectively. Morphothiadin has a bioavailability of 25.5%. It is discovered that the mice treated with 3.75 mg/kg of morphothiadin per day had an increase in virus titers of 83.5 times, the mice treated with 7.5 mg/kg per day had an increase of 28.3 times, and the mice treated with the higher doses of morphothiadin had an increase of only 3 to 6 times.The amount of morphothiadin and the virus titer are generally inversely correlated; mice treated with 3.75 mg/kg of morphothiadin per day showed the largest rebound (540-fold), while mice treated with 60 mg/kg per day showed the smallest rebound (23-fold) (P<0.001). During the course of treatment, phothiadin doses exceeding 7.5 mg/kg per day significantly suppress the virus replication cycle. Moreover, phothiadin doses exceeding 15 mg/kg per day continue to suppress the virus for up to two weeks following the end of treatment[2].
|
| Enzyme Assay |
Dog and human liver microsomes and CYP3A4 were incubated with [(14)C]GLS4 for 15 min and then analyzed using a HPLC-dynamic online radio flow detection method. Two groups of beagle dogs were used for in vivo studies. Group A were orally administered a single dose of GLS4 (15 mg/kg) with or without ketoconazole pretreatment (100 mg/d for 8 consecutive days). Group B were orally administered a single dose of GLS4 (15 mg/kg) with or without rifampicin pretreatment (100 mg/d for 8 consecutive days). Plasma was sampled after GLS4 dosing. GLS4 concentrations were determined by HPLC-tandem mass spectrometry [1].
|
| Cell Assay |
Tetracycline (0.3 μg/mL) is used to grow HepAD38 cells to approximately 80% confluence. Following TET removal, the cells are either left untreated or given varying dosages of morphothiadin (GLS4). The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay is used to measure cell viability[2].
|
| Animal Protocol |
The pharmacokinetic (PK) characteristics of morphothiadin (GLS4) are assessed in ICR mice. Liquid chromatography-tandem mass spectrometry (LC/MS/MS) is used to measure the amount of morphothiadin in plasma after oral administration of 10 mg/kg (of body weight) to male mice. ICR mice are given morphothiadin by gavage over a 4-week period for toxicity studies, after which they are kept off medication for an additional 2-week period. Twenty male and twenty female mice per group are given a vehicle (1% methyl-2-hydroxyethyl cellulose) at doses of 35.7, 118.9, or 356.6 mg/kg daily in a volume equivalent to 20 mL/kg. Two weeks after the end of the drug treatment, ten mice per dose group are put to death. Serum albumin levels, body weight, food intake, and side effects are calculated[2].
|
| References |
|
| Molecular Formula |
C21H22BRFN4O3S
|
|---|---|
| Molecular Weight |
509.39178609848
|
| Exact Mass |
508.06
|
| Elemental Analysis |
C, 49.52; H, 4.35; Br, 15.69; F, 3.73; N, 11.00; O, 9.42; S, 6.29
|
| CAS # |
1092970-12-1
|
| Related CAS # |
1793065-08-3 (R-isomer);2093044-32-5 (S-isomer);1092970-12-1 (racemic);1646361-04-7 (mesylate);
|
| PubChem CID |
25144422
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
2.5
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
31
|
| Complexity |
719
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
SQGRDKSRFFUBBU-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C21H22BrFN4O3S/c1-2-30-21(28)17-16(12-27-6-8-29-9-7-27)25-19(20-24-5-10-31-20)26-18(17)14-4-3-13(23)11-15(14)22/h3-5,10-11,18H,2,6-9,12H2,1H3,(H,25,26)
|
| Chemical Name |
ethyl 4-[2-bromo-4-fluorophenyl]-6-[morpholino-methyl]-2-[2-thiazolyl]-1,4-dihydro-pyrimidine-5-carboxylate
|
| Synonyms |
Morphothiadine; GLS-4; GLS 4.
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~62.5 mg/mL (~122.70 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3 mg/mL (5.89 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 3 mg/mL (5.89 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9631 mL | 9.8157 mL | 19.6313 mL | |
| 5 mM | 0.3926 mL | 1.9631 mL | 3.9263 mL | |
| 10 mM | 0.1963 mL | 0.9816 mL | 1.9631 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| Cell Assay |
|---|
| Animal Admin |
|---|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA