Inactive form of colchine

Colchicine and Lumicolchicine as triggers of Mallory bodies (MBs)[1]
After administration of colchicine to 2.5 months DDC- or 4 months GF-primed and recovered mice necrotic, apoptotic but also mitotic hepatocytes were dispersed throughout the lobule. Hepatocytes with vacuolated cytoplasm predominated in the centrilobular area. In GF-primed mice the colchicine-induced damage was less pronounced than in the DDC animals. Small granular MBs occured mostly in cells with loosely arranged IF bundles in both groups (Fig. 4a). In many enlarged cells clumps of MB material were seen at the cell periphery and in association with the canalicular membrane suggesting appositional growth of residual MBs.

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Keratin mRNA and protein expression during DDC and GF intoxication [1]
Intoxication with DDC rapidly led to a five-fold overexpression of keratins 8 and 18 mRNA, which persisted for 2.5 months and returned to control levels within 1 month of recovery (Fig. 8a). DDC reintoxicaton for 3 days resulted in an even more pronounced (eight-fold) keratin mRNA overexpression. GF treatment had a similar effect. Colchicine also stimulated keratin mRNA expression in primed mice whereas Lumicolchicine was only marginally effective. Keratin protein rose in DDC- (Fig. 8b) and GF-intoxicated mice reaching a maximum after 1 week. In livers of mice intoxicated for 2 and 2.5 months keratin protein levels were still significantly elevated yet lower than in short-term intoxicated animals. It is noteworthy that the increase of keratin 8 exceeded that of keratin 18. In the recovery phase keratins returned to control levels and rose again upon refeeding. [1]

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Duration of pretreatment was important for the efficiency of MB triggering. Rapid increase of keratin 8/18 mRNA and proteins was found in all reintoxicated mice concomitant with MB formation, whereby keratin 8 prevailed over keratin 18. Keratins and a protein with heat shock characteristics (M(M) 120-1 antigen) were the earliest detectable MB components, whereas ubiquitination and phosphorylation followed later. Conclusions: Overproduction of keratins is a major but not the only step responsible for MB formation. Additional components (e.g. M(M) 120-1 antigen) and excess of keratin 8 over keratin 18 are essential [1].

Male Swiss Albino mice (35 g body weight; strain Him OF1 SPF) received a standard diet containing 2.5% GF (Sigma, St.Louis, MO) for 1, 4 and 5 months and 0.1% DDC for 1, 2, 2.5 and 5.5 months, respectively. Thereafter the animals recovered on standard diet for 1 month (‘priming’). They were reintoxicated with GF (2.5%) or DDC (0.1%) for 1, 2, 3 and 7 days. Normal mice were also treated with GF or DDC for 1, 2, 3 and 7 days. Primed animals also received DDC intraperitoneally (10 mg/day) for 2 days, colchicine (4×10 μg, subcutaneous injections within 2 days) or Lumicolchicine (same schedule). Lumicolchicine was prepared by irradiation of 1 mM colchicine in 95% ethanol at 366 nm for 1 h. GF-pre-treated mice were also reintoxicated with DDC and vice versa. Animals on normal diet served as controls. Mice (at least three at each time point) were decapitated and pieces of liver were snap-frozen in methylbutane precooled with liquid nitrogen for immunohistochemistry, or frozen in liquid nitrogen for RNA preparation and immunoblotting. For light microscopy, 4% paraformaldehyde-fixed specimens were embedded in paraffin; 4 μm thick sections were stained with hematoxylin-eosin and chromotrope aniline blue, respectively. [1]

[1]. Sequence of events in the assembly of Mallory body components in mouse liver: clues to the pathogenesis and significance of Mallory body formation. J Hepatol. 2001 May;34(5):665-75.

LSM-4236 is a carbotricyclic compound, a member of acetamides and an alkaloid.
beta-Lumicolchicine has been reported in Colchicum arenarium, Colchicum autumnale, and other organisms with data available.
Three, alpha, beta, and gamma isomers of ultraviolet degradation products of colchicine that lack many of the physiological actions of the parent; used as experimental control for colchicine actions.
See also: gamma-Lumicolchicine (annotation moved to).

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Background/aims: Chronic intoxication of mice with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) or griseofulvin (GF) results in appearance of Mallory bodies (MBs) and alterations of the keratin cytoskeleton, which are reversible upon drug withdrawal but recur after readministration within 2-3 days. Methods: DDC- or GF-treated and recovered mice were reintoxicated with the original drugs but also colchicine and lumicolchicine. Cytoskeletal alterations of hepatocytes and MB formation were monitored by immunofluorescence microscopy using keratin, MB-specific antibodies, antibodies to phosphoepitopes and to HSP70. Keratin 8/18 mRNA expression and protein levels were determined by competitive reverse transcription-polymerase chain reaction, in situ-hybridization and western blotting. Results: Duration of pretreatment was important for the efficiency of MB triggering. Rapid increase of keratin 8/18 mRNA and proteins was found in all reintoxicated mice concomitant with MB formation, whereby keratin 8 prevailed over keratin 18. Keratins and a protein with heat shock characteristics (M(M) 120-1 antigen) were the earliest detectable MB components, whereas ubiquitination and phosphorylation followed later. Conclusions: Overproduction of keratins is a major but not the only step responsible for MB formation. Additional components (e.g. M(M) 120-1 antigen) and excess of keratin 8 over keratin 18 are essential. [1]

C22H25NO6

399.443

399.168

C, 66.15; H, 6.31; N, 3.51; O, 24.03

6901-13-9

6901-13-9; 6901-14-0

244898

Typically exists as solid at room temperature

1.3g/cm3

623.2ºC at 760mmHg

177-180ºC

330.7ºC

1.596

2.666

1

6

5

29

758

3

CC(=O)NC1CCC2=CC(=C(C(=C2C3=C1C4C3C=C(C4=O)OC)OC)OC)OC

VKPVZFOUXUQJMW-FHSNZYRGSA-N

InChI=1S/C22H25NO6/c1-10(24)23-13-7-6-11-8-15(27-3)21(28-4)22(29-5)16(11)17-12-9-14(26-2)20(25)18(12)19(13)17/h8-9,12-13,18H,6-7H2,1-5H3,(H,23,24)/t12-,13+,18-/m1/s1

N-[(10S,12R,16S)-3,4,5,14-tetramethoxy-13-oxo-10-tetracyclo[9.5.0.02,7.012,16]hexadeca-1(11),2,4,6,14-pentaenyl]acetamide

Lumicolchicine; 6901-13-9; beta-Lumicolchicine; gamma-Lumicolchicine; Lumicolchicine gamma; [7S-(7alpha,7bbeta,10abeta)]-N-(5,6,7,7b,8,10a-hexahydro-1,2,3,9-tetramethoxy-8-oxobenzo[a]cyclopenta[3,4]cyclobuta[1,2-c]cyclohepten-7-yl)acetamide; .beta.-Lumicolchicine; beta-Lumi (-)-Colchicine;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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

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.

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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 : 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).

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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 : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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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

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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.

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 (Please use freshly prepared in vivo formulations for optimal results.)