Synonym
Mezerein; CCRIS4674; CCRIS-4674; CCRIS 4674
IUPAC/Chemical Name
(3aR,3bS,3cS,5S,5aS,8aR,8bR,9R,10R,10aS)-5,5a-dihydroxy-4a-(hydroxymethyl)-7,9-dimethyl-6-oxo-2-phenyl-10a-(prop-1-en-2-yl)-3a,3b,3c,4a,5,5a,8a,9,10,10a-decahydro-6H-2,8b-epoxyoxireno[2'',3'':6',7']azuleno[5',4':3,4]benzo[1,2-d][1,3]dioxol-10-yl (2E,4E)-5-phenylpenta-2,4-dienoate
InChi Key
DLEDLHFNQDHEOJ-CSWXFLMBSA-N
InChi Code
InChI=1S/C38H38O10/c1-21(2)36-30(44-27(40)18-12-11-15-24-13-7-5-8-14-24)23(4)37-26-19-22(3)29(41)35(26,43)33(42)34(20-39)31(45-34)28(37)32(36)46-38(47-36,48-37)25-16-9-6-10-17-25/h5-19,23,26,28,30-33,39,42-43H,1,20H2,2-4H3/b15-11+,18-12+/t23-,26-,28+,30-,31+,32-,33-,34?,35-,36+,37+,38?/m1/s1
SMILES Code
C[C@@H]1[C@H]([C@]2(C(C)=C)OC3(c4ccccc4)O[C@@H]2[C@@H]5[C@@H]6OC6([C@H]([C@]7([C@H]([C@@]15O3)C=C(C7=O)C)O)O)CO)OC(/C=C/C=C/c8ccccc8)=O
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
To be determined
Shelf Life
>2 years if stored properly
Drug Formulation
to be determined
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
Mezerein is a PKC activator that exhibits antileukemic properties.
In vitro activity:
Yeast samples expressing each of the mammalian PKC isoforms tested were incubated with daphnetoxin or mezerein. Mezerein inhibited the growth of yeast expressing PKC alpha (IC(50) = 1190 +/- 237 nM; n = 20), PKC beta I (IC(50) = 908 +/- 46 nM; n = 20), and PKC delta (IC(50) = 141 +/- 25 nM; n = 20) but not of yeast expressing PKC zeta.
Reference: Planta Med. 2001 Dec;67(9):787-90. https://pubmed.ncbi.nlm.nih.gov/11745011/
In vivo activity:
Promotion of MNNG-initiated skin with mezerein induced the appearance of very rapidly-growing papillomas within 5 wk, 3 wk earlier than the first TPA-promoted papillomas. Surprisingly, 41% of the papillomas arising in the first 11 wk in MNNG-initiated, mezerein-promoted mice bore mutations in codon 12 of the Ki-ras oncogene.
Reference: Mol Carcinog. 2000 Apr;27(4):298-307. https://pubmed.ncbi.nlm.nih.gov/10747294/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| To be determined |
0.0 |
100.00 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
654.71
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Wu SH, Liu B, Dong L, Wu HJ. NF-kappaB is involved in inhibition of lipoxin A4 on dermal inflammation and hyperplasia induced by mezerein. Exp Dermatol. 2010 Aug;19(8):e286-8. doi: 10.1111/j.1600-0625.2009.00981.x. PMID: 20100194.
2. Saraiva L, Fresco P, Pinto E, Portugal H, Gonçalves J. Differential activation by daphnetoxin and mezerein of PKC-isotypes alpha, beta I, delta and zeta. Planta Med. 2001 Dec;67(9):787-90. doi: 10.1055/s-2001-18843. PMID: 11745011.
3. Rehman I, Lowry DT, Adams C, Abdel-Fattah R, Holly A, Yuspa SH, Hennings H. Frequent codon 12 Ki-ras mutations in mouse skin tumors initiated by N-methyl-N'-nitro-N-nitrosoguanidine and promoted by mezerein. Mol Carcinog. 2000 Apr;27(4):298-307. PMID: 10747294.
4. Chen LC, Tarone R, Huynh M, De Luca LM. High dietary retinoic acid inhibits tumor promotion and malignant conversion in a two-stage skin carcinogenesis protocol using 7,12-dimethylbenz[a]anthracene as the initiator and mezerein as the tumor promoter in female SENCAR mice. Cancer Lett. 1995 Aug 16;95(1-2):113-8. doi: 10.1016/0304-3835(95)03868-w. PMID: 7656218.
In vitro protocol:
1. Wu SH, Liu B, Dong L, Wu HJ. NF-kappaB is involved in inhibition of lipoxin A4 on dermal inflammation and hyperplasia induced by mezerein. Exp Dermatol. 2010 Aug;19(8):e286-8. doi: 10.1111/j.1600-0625.2009.00981.x. PMID: 20100194.
2. Saraiva L, Fresco P, Pinto E, Portugal H, Gonçalves J. Differential activation by daphnetoxin and mezerein of PKC-isotypes alpha, beta I, delta and zeta. Planta Med. 2001 Dec;67(9):787-90. doi: 10.1055/s-2001-18843. PMID: 11745011.
In vivo protocol:
1. Rehman I, Lowry DT, Adams C, Abdel-Fattah R, Holly A, Yuspa SH, Hennings H. Frequent codon 12 Ki-ras mutations in mouse skin tumors initiated by N-methyl-N'-nitro-N-nitrosoguanidine and promoted by mezerein. Mol Carcinog. 2000 Apr;27(4):298-307. PMID: 10747294.
2. Chen LC, Tarone R, Huynh M, De Luca LM. High dietary retinoic acid inhibits tumor promotion and malignant conversion in a two-stage skin carcinogenesis protocol using 7,12-dimethylbenz[a]anthracene as the initiator and mezerein as the tumor promoter in female SENCAR mice. Cancer Lett. 1995 Aug 16;95(1-2):113-8. doi: 10.1016/0304-3835(95)03868-w. PMID: 7656218.
1: Ewing MW, Conti CJ, Phillips JL, Slaga TJ, DiGiovanni J. Further characterization of skin tumor promotion and progression by mezerein in SENCAR mice. J Natl Cancer Inst. 1989 May 3;81(9):676-82. doi: 10.1093/jnci/81.9.676. PMID: 2496233.
2: Saraiva L, Fresco P, Pinto E, Portugal H, Gonçalves J. Differential activation by daphnetoxin and mezerein of PKC-isotypes alpha, beta I, delta and zeta. Planta Med. 2001 Dec;67(9):787-90. doi: 10.1055/s-2001-18843. PMID: 11745011.
3: Kupchan SM, Baxter RL. Mezerein: antileukemic principle isolated from Daphne mezereum L. Science. 1975 Feb 21;187(4177):652-3. doi: 10.1126/science.1114315. PMID: 1114315.
4: Ewing MW, Crysup SE, Phillips JL, Slaga TJ, DiGiovanni J. Enhancement of mezerein-promoted papilloma formation by treatment with 12-O-tetradecanoylphorbol-13-acetate or mezerein prior to initiation. Carcinogenesis. 1988 Mar;9(3):405-10. doi: 10.1093/carcin/9.3.405. PMID: 3125993.
5: Jin YX, Shi LL, Zhang DP, Wei HY, Si Y, Ma GX, Zhang J. A Review on Daphnane- Type Diterpenoids and Their Bioactive Studies. Molecules. 2019 May 13;24(9):1842. doi: 10.3390/molecules24091842. PMID: 31086098; PMCID: PMC6540581.
6: Miller ML, Andringa A, Baxter CS. Critical comparison of histological and morphometric changes in SENCAR mouse epidermis in response to n-dodecane, 12-O-tetradecanoylphorbol-13-acetate and mezerein. Carcinogenesis. 1988 Nov;9(11):1959-65. doi: 10.1093/carcin/9.11.1959. PMID: 3180333.
7: Riaz M, Saleem A, Siddique S, Khan BA, Nur-e-Alam M, Shahzad-ul-Hussan S, Miana GA, Khan MQ. Phytochemistry of Daphne oleoides. Nat Prod Res. 2016;30(8):880-97. doi: 10.1080/14786419.2015.1092146. Epub 2015 Nov 14. PMID: 26567755.
8: Barton K, Randall G, Sagone AL Jr. The effects of the anti-tumor agent mezerein on the cytotoxic capacity and oxidative metabolism of human blood cells. Invest New Drugs. 1989 Jul;7(2-3):179-88. doi: 10.1007/BF00170855. PMID: 2793370.
9: Ronlán A, Wickberg B. The structure of mezerein, a major toxic principle of Daphne mezereum L. Tetrahedron Lett. 1970 Oct;(49):4261-4. doi: 10.1016/s0040-4039(00)89459-9. PMID: 5495053.
10: Ohmura E, Tsushima T, Emoto N, Obuchi E, Shizume K. Effects of tumor promoters (mezerein, teleocidin and palytoxin) on growth hormone secretion from rat anterior pituitary cells cultured in monolayer. Life Sci. 1987 Aug 10;41(6):691-6. doi: 10.1016/0024-3205(87)90448-6. PMID: 2886871.
