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Manumycin A

Cat No.:V13505 Purity: ≥98%
Manumycin A is an antibiotic.
Manumycin A
Manumycin A Chemical Structure CAS No.: 52665-74-4
Product category: New1
This product is for research use only, not for human use. We do not sell to patients.
Size Price Stock Qty
1mg
Other Sizes
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Product Description
Manumycin A is an antibiotic. Manumycin A works as a selective, competitive inhibitor of farnesyltransferase (FTase), related to farnesylpyrophosphate (Ki =1.2 μM), and as a noncompetitive inhibitor of Ras proteins. Manumycin A causes apoptosis and exerts anti-tumor effects. Manumycin A inhibits exosome biogenesis and secretion by targeting Ras/Raf/ERK1/2 signal transduction. Manumycin A is also an nSMase inhibitor (EC50=0.25 μM).
Biological Activity I Assay Protocols (From Reference)
References

[1]. Manumycin A downregulates release of proinflammatory cytokines from TNF alpha stimulated human monocytes. Immunol Lett. 2016 Jan;169:8-14.

[2]. Inhibition of the Heat Shock Protein A (HSPA) Family Potentiates the Anticancer Effects of Manumycin A. Cells. 2021 Jun 7;10(6):1418.

[3]. Manumycin A inhibits triple-negative breast cancer growth through LC3-mediated cytoplasmic vacuolation death. Cell Death Dis. 2013 Jan 17;4(1):e457.

[4]. Manumycin A suppresses exosome biogenesis and secretion via targeted inhibition of Ras/Raf/ERK1/2 signaling and hnRNP H1 in castration-resistant prostate cancer cells. Cancer Lett. 2017 Nov 1;408:73-81.

[5]. Manumycin A corrects aberrant splicing of Clcn1 in myotonic dystrophy type 1 (DM1) mice. Sci Rep. 2013;3:2142.

Additional Infomation
Manumycin A is a polyketide with formula C31H38N2O7 initially isolated from Streptomyces parvulus as a result of a random screening program for farnesyl transferase (FTase) inhibitors. It is a natural product that exhibits anticancer and antibiotic properties. It has a role as an EC 1.8.1.9 (thioredoxin reductase) inhibitor, an EC 2.5.1.58 (protein farnesyltransferase) inhibitor, an antineoplastic agent, an apoptosis inducer, an antimicrobial agent, a bacterial metabolite, an antiatherosclerotic agent and a marine metabolite. It is a polyketide, an enamide, an epoxide, an organic heterobicyclic compound, a secondary carboxamide and a tertiary alcohol.
Manumycin A has been reported in Streptomyces, Streptomyces griseoaurantiacus, and Streptomyces parvulus with data available.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C31H38N2O7
Molecular Weight
550.64262
Exact Mass
550.267
CAS #
52665-74-4
PubChem CID
6438330
Appearance
Yellow to orange solid powder
Density
1.3±0.1 g/cm3
Boiling Point
863.6±65.0 °C at 760 mmHg
Flash Point
476.1±34.3 °C
Vapour Pressure
0.0±0.6 mmHg at 25°C
Index of Refraction
1.605
LogP
3.04
Hydrogen Bond Donor Count
4
Hydrogen Bond Acceptor Count
7
Rotatable Bond Count
12
Heavy Atom Count
40
Complexity
1260
Defined Atom Stereocenter Count
4
SMILES
CCCC[C@@H](C)/C=C(\C)/C=C(\C)/C(=O)NC1=C[C@]([C@H]2[C@@H](C1=O)O2)(/C=C/C=C/C=C/C(=O)NC3=C(CCC3=O)O)O
InChi Key
TWWQHCKLTXDWBD-MVTGTTCWSA-N
InChi Code
InChI=1S/C31H38N2O7/c1-5-6-11-19(2)16-20(3)17-21(4)30(38)32-22-18-31(39,29-28(40-29)27(22)37)15-10-8-7-9-12-25(36)33-26-23(34)13-14-24(26)35/h7-10,12,15-19,28-29,34,39H,5-6,11,13-14H2,1-4H3,(H,32,38)(H,33,36)/b8-7+,12-9+,15-10+,20-16+,21-17+/t19-,28-,29-,31+/m1/s1
Chemical Name
(2E,4E,6R)-N-[(1S,5S,6R)-5-hydroxy-5-[(1E,3E,5E)-7-[(2-hydroxy-5-oxocyclopenten-1-yl)amino]-7-oxohepta-1,3,5-trienyl]-2-oxo-7-oxabicyclo[4.1.0]hept-3-en-3-yl]-2,4,6-trimethyldeca-2,4-dienamide
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, avoid exposure to moisture.
Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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
(e.g. IP/IV/IM/SC)
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution 50 μL Tween 80 850 μL Saline)
*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 : PEG300Tween 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).
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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)]
*Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO 100 μLPEG300 200 μL castor oil 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10: 10 : 80 (i.e. 100 μL Ethanol 100 μL Cremophor 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH 400 μLPEG300 50 μL Tween 80 450 μL 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).
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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders


Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 1.8161 mL 9.0803 mL 18.1607 mL
5 mM 0.3632 mL 1.8161 mL 3.6321 mL
10 mM 0.1816 mL 0.9080 mL 1.8161 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.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

  • Calculate the Mass of a compound required to prepare a solution of known volume and concentration
  • Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
  • Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume
An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
  • To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

  • Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
  • Click the “Calculate” button
  • The answer appears in the Volume (to add to vial) box
In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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.

Biological Data
  • NSCLC cell lines show different sensitivity to manumycin A (MA). (a) The basal levels of MA targets in NSCLC cells. Representative immunoblots are shown (n ≥ 3); actin or HSPA8 were used as a protein loading control. Numbers on the left or right side of the blots indicate molecular weight of a protein size marker. (b) Dose-response curves of MA in NSCLC cell lines. Cell viability was measured following 72 h treatment with MA (0–50 µM) using an MTS assay. Results (mean ± SD from at least four independent measurements, each in three technical replicates) are expressed relatively to untreated control.[2]. Inhibition of the Heat Shock Protein A (HSPA) Family Potentiates the Anticancer Effects of Manumycin A. Cells. 2021 Jun 7;10(6):1418.
  • Manipulations in the protein levels of HSPA1 and HSPA2 have limited effect on sensitivity of NSCLC cells to manumycin A (MA). (a,c) Immunoblots showing levels of HSPA1 and HSPA2 in wild-type (wt) and lentivirally-modified cells; sh-luc control cells were transduced with a non-targeting shRNA-luc sequence; sh-A1.N and sh-A1.S cell lines were transduced with HSPA1-targeting shRNA sequences; control p-LVX cells were transduced with lentiviruses bearing the “empty” pLVX-Puro vector; p-A2 cells were transduced with pLVX-Puro plasmid encoding HSPA2 protein under the control of the CMV promoter; sh-A2.3 and sh-A2.4 cell lines were transduced with HSPA2-targeting shRNA sequences. Representative immunoblots are shown (n ≥ 3); actin was used as a protein loading control. These model cell lines were described in detail previously [26,27]. (b,d) Cell viability was measured using MTS assay after 72 h treatment with MA (0–10 µM). Results are expressed as mean ± SD in relation to untreated control (n = 4, each in three technical replicates, * p < 0.05, statistical significance was determined by two-tailed t-test). The numbers on the right side of immunoblots indicate molecular weight of the protein size marker.[2]. Inhibition of the Heat Shock Protein A (HSPA) Family Potentiates the Anticancer Effects of Manumycin A. Cells. 2021 Jun 7;10(6):1418.
  • Effects of single or combined treatment (72 h) with (a,c,f,g) VER-155008 (VER) and manumycin A (MA) or (b,d,e) JG-98 and MA. Cell viability (a–e) was measured using MTS assay. Results are expressed in relation to the untreated control (mean ± SD, n ≥ 3, each in triplicate). Cytotoxicity (f,g) was evaluated using the CellTox™ cytotoxicity assay (mean ± SD, n ≥ 3, each in duplicate). Statistical significance was determined using two-tailed t-test; * p < 0.05, differences were considered significant if the value obtained for a double treatment was significantly different (p < 0.05) from the value obtained for each of the single treatments; # p < 0.05, statistical significance determined for single treatments (f,g).[2]. Inhibition of the Heat Shock Protein A (HSPA) Family Potentiates the Anticancer Effects of Manumycin A. Cells. 2021 Jun 7;10(6):1418.
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