| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg | |||
| Other Sizes |
| Targets |
GSK-3β 10.2 μM (IC50) Plasmodium CDK5 1.5 μM (IC50) vacuolar ATPases Malaria HSV-1
Manzamine A hydrochloride targets multiple biological targets, contributing to its diverse pharmacological activities. It inhibits GSK-3beta (IC₅0 = 10.2 microM) and CDK-5 (IC₅0 = 1.5 microM), two kinases involved in cell signaling, neuronal function, and cancer. The compound also targets vacuolar ATPases (V-ATPases), which are proton pumps essential for acidifying intracellular compartments and regulating autophagy. By inhibiting V-ATPases, Manzamine A hydrochloride blocks autophagic flux, leading to the accumulation of autophagosomes and induction of cell death in pancreatic cancer cells. Its antiviral activity against HSV-1 is mediated through an unknown mechanism. |
|---|---|
| ln Vitro |
Manzamine A (5-50 µM, 18 h) hydrochloride reduces tau phosphorylation as determined by ELISA[1]. Manzamine A (10 µM) hydrochloride inhibits 30% of the development of yeast S. cerevisiae[2]. In yeast, manzamine A hydrochloride exhibits a few expanded vacuoles[2]. Pancreatic cancer cells and non-malignant Vero cells exhibit increased acidity in response to manzamine A (2.5-10 µM, 24 h) hydrochloride[2]. In SIRC cells, HSV-1 infection is inhibited by manzamine A (1 µM, 24 h) hydrochloride[4]. The antimalarial activity of manzamine A hydrochloride is demonstrated by IC50 values of 8.0 nM (D6 clone) and 11 nM (W2 clone)[5].
In vitro studies demonstrate that Manzamine A hydrochloride is a potent inhibitor of GSK-3beta and CDK-5 with IC₅0 values of 10.2 microM and 1.5 microM, respectively. The compound inhibits autophagy in pancreatic cancer cells by targeting vacuolar ATPases. It exhibits antimalarial activity and anticancer activity against various cancer cell lines. Manzamine A hydrochloride also shows potent activity against HSV-1. Its in vitro activity is assessed using enzyme assays for kinase inhibition, cell viability assays, autophagy flux assays (LC3-II accumulation), and antiviral plaque reduction assays. |
| ln Vivo |
Infected mice treated with manzamine A (50 and 100 mol/kg, po or ip) hydrochloride do not develop the rodent malaria parasite Plasmodium berghei [6]. Swine survival is extended to 20 days with manzamine A (8 mg/kg, ip, daily for 8 consecutive days) hydrochloride[7].
In vivo studies demonstrate that Manzamine A hydrochloride is orally active. It exhibits antimalarial activity in animal models and anticancer efficacy in xenograft studies. The compound also shows antiviral activity in vivo, though detailed data are limited. Its ability to inhibit autophagy and target V-ATPases contributes to its anticancer activity. The compound's oral bioavailability makes it a promising lead for drug development. In vivo efficacy is typically assessed by measuring tumor growth inhibition, parasite clearance, or viral load reduction in appropriate animal models. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for Manzamine A hydrochloride involve measuring its inhibition of GSK-3beta and CDK-5 kinase activity. The assay typically uses purified recombinant kinases, a peptide substrate, and ATP. The compound is incubated with the enzyme and substrates at 30degC, and phosphorylation is quantified by scintillation counting using radiolabeled ATP or by ELISA. IC₅0 values are calculated from dose-response curves. V-ATPase inhibition is assessed by measuring proton pump activity using isolated membrane fractions or purified V-ATPase, with ATPase activity measured colorimetrically.
|
| Cell Assay |
Cell Viability Assay[4]
Cell Types: SIRC cell Tested Concentrations: 0.1, 0.5, 1, 2, 3, 5, and 10 µM Incubation Duration: 72 h Experimental Results: Inhibited SIRC cell viability with an IC50 of 5.6 µM. Cellular assays for Manzamine A hydrochloride are conducted using cancer cell lines, particularly pancreatic cancer cells, to evaluate its effects on autophagy, cell viability, and apoptosis. Cells are treated with varying concentrations of the compound (typically 0.1-100 microM) for 24-72 hours. Autophagy is assessed by measuring LC3-II accumulation, p62 degradation, and autophagosome formation using Western blotting or immunofluorescence microscopy. Cell viability is assessed using MTT or similar assays. Apoptosis is evaluated by Annexin V/PI staining or caspase activity. Antiviral activity against HSV-1 is assessed using plaque reduction assays in Vero cells. |
| Animal Protocol |
Animal/Disease Models: Plasmodium berghei in infected mice[6]
Doses: 50 or 100 mol/kg Route of Administration: intraperitoneal (ip)injection or oral administration (po) Experimental Results: Inhibited the growth of the rodent malaria parasite Plasmodium berghei. Prolonged the survival of highly parasitaemic mice. In vivo animal studies with Manzamine A hydrochloride are conducted in models of malaria, cancer, and viral infection. For antimalarial studies, mice infected with Plasmodium species are treated with the compound orally at various doses, and parasitemia is monitored. For anticancer studies, xenograft models using pancreatic cancer cell lines are employed, with tumor growth inhibition measured. For antiviral studies, animal models of HSV-1 infection may be used, though detailed protocols are limited. Pharmacokinetic studies are also performed to assess oral bioavailability and tissue distribution. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of Manzamine A hydrochloride demonstrate that the compound is orally active. Its molecular weight is 585.22 g/mol and its molecular formula is C3₆H4₅ClN4O. The hydrochloride salt enhances aqueous solubility. Following oral administration, the compound is absorbed and distributed to various tissues, including the brain. Its pharmacokinetic profile is characteristic of beta-carboline alkaloids, with potential for good bioavailability. Detailed PK parameters such as half-life, Cmax, and AUC are not extensively reported in the available literature.
|
| Toxicity/Toxicokinetics |
Toxicological data for Manzamine A hydrochloride are limited, as the compound is primarily used as a research tool. The compound is not intended for human therapeutic use and is supplied for research purposes only. In cell-based assays, the compound exhibits cytotoxic activity against cancer cells at micromolar concentrations, suggesting potential toxicity at higher doses. In animal studies, the compound is generally well-tolerated at standard dosing ranges, though specific toxicity profiles are not extensively reported. Standard safety precautions should be followed when handling this compound.
|
| References |
|
| Additional Infomation |
Manzamine A hydrochloride is an orally active beta-carboline alkaloid with diverse biological activities including antitumor, antimicrobial, antimalarial, and antiviral properties. It specifically inhibits GSK-3beta (IC₅0 = 10.2 microM) and CDK-5 (IC₅0 = 1.5 microM). The compound targets vacuolar ATPases and inhibits autophagy in pancreatic cancer cells. It also demonstrates potent activity against HSV-1. The compound is not an FDA-approved drug and has no clinical indications. It is available in high purity and is typically stored at -20degC.
|
| Molecular Formula |
C36H44N4O
|
|---|---|
| Molecular Weight |
548.761
|
| Exact Mass |
584.328
|
| CAS # |
104264-80-4
|
| Related CAS # |
Manzamine A;104196-68-1
|
| PubChem CID |
49797386
|
| Appearance |
Light yellow to brown solid powder
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
42
|
| Complexity |
1050
|
| Defined Atom Stereocenter Count |
5
|
| SMILES |
C123C([H])([H])C4(C(=C(C(C(C(C([H])([H])N4C1(C1(C(=C(c4c5[n]([H])c6c(c(c(c([H])c6c5c([H])c([H])n4)[H])[H])[H])C2([H])C([H])([H])C([H])([H])N(C(C(C(C(C(=C(C(C1([H])[H])([H])[H])[H])[H])([H])[H])([H])[H])([H])[H])([H])[H])C3([H])[H])[H])O[H])[H])([H])[H])([H])[H])([H])[H])[H])[H])[H]
|
| InChi Key |
DIVWQABXFSWTEF-YTGAITGWSA-N
|
| InChi Code |
InChI=1S/C36H44N4O.ClH/c41-36-18-10-4-1-2-5-11-20-39-22-17-30(35(25-39)23-26-13-7-3-6-12-21-40(26)34(35)36)29(24-36)32-33-28(16-19-37-32)27-14-8-9-15-31(27)38-33;/h1,4,7-9,13-16,19,24,26,30,34,38,41H,2-3,5-6,10-12,17-18,20-23,25H2;1H/b4-1-,13-7-;/t26-,30-,34+,35-,36-;/m0./s1
|
| Chemical Name |
(1R,2R,4R,5Z,12R,13S,16Z)-25-(9H-pyrido[3,4-b]indol-1-yl)-11,22-diazapentacyclo[11.11.2.12,22.02,12.04,11]heptacosa-5,16,25-trien-13-ol;hydrochloride
|
| 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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 : 5.88 mg/mL (10.05 mM)
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8223 mL | 9.1115 mL | 18.2229 mL | |
| 5 mM | 0.3645 mL | 1.8223 mL | 3.6446 mL | |
| 10 mM | 0.1822 mL | 0.9111 mL | 1.8223 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
