UCN-02
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| Category | Enzyme inhibitors |
| Catalog number | BBF-01898 |
| CAS | 121569-61-7 |
| Molecular Weight | 482.53 |
| Molecular Formula | C28H26N4O4 |
| Purity | >95% by HPLC |
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Description
UCN-02 is an indolocarbazole isolated from a high staurosporine-producing Streptomyces culture with antineoplastic activity. It inhibits many phosphokinases, including the serine/threonine kinase AKT, calcium-dependent protein kinase C, and cyclin-dependent kinases.
Specification
| Synonyms | Antibiotic UCN 02; UCN02; GNF-Pf-3072; 7-hydroxy-staurosporine; 7-epi-Hydroxystaurosporine; (3S,9S,10R,11R,13R)-2,3,10,11,12,13-Hexahydro-3-hydroxy-10-methoxy-9-methyl-11-(methylamino)-9,13-epoxy-1H,9H-diindolo[1,2,3-gh:3',2',1'-lm]pyrrolo[3,4-j][1,7]benzodiazonin-1-one; [3S-(3α,9α,10β,11β,13α)]-2,3,10,11,12,13-Hexahydro-3-hydroxy-10-methoxy-9-methyl-11-(methylamino)-9,13-epoxy-1H,9H-diindolo[1,2,3-gh:3',2',1'-lm]pyrrolo[3,4-j][1,7]benzodiazonin-1-one |
| Storage | Store at -20°C |
| IUPAC Name | (2S,3R,4R,6R,18S)-18-hydroxy-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one |
| Canonical SMILES | CC12C(C(CC(O1)N3C4=CC=CC=C4C5=C6C(=C7C8=CC=CC=C8N2C7=C53)C(NC6=O)O)NC)OC |
| InChI | InChI=1S/C28H26N4O4/c1-28-25(35-3)15(29-2)12-18(36-28)31-16-10-6-4-8-13(16)19-21-22(27(34)30-26(21)33)20-14-9-5-7-11-17(14)32(28)24(20)23(19)31/h4-11,15,18,25,27,29,34H,12H2,1-3H3,(H,30,33)/t15-,18-,25-,27+,28+/m1/s1 |
| InChI Key | PBCZSGKMGDDXIJ-KRUBCLEUSA-N |
| Source | Streptomyces sp. |
Properties
| Appearance | Pale Yellow Crystal |
| Antibiotic Activity Spectrum | Neoplastics (Tumor) |
| Boiling Point | 705.7±60.0°C (Predicted) |
| Melting Point | 245-250°C |
| Density | 1.63±0.1 g/cm3 (Predicted) |
| Solubility | Soluble in Ethanol, Methanol, DMF, DMSO |
Reference Reading
1. 7-hydroxy-staurosporine, UCN-01, induces DNA damage response, and autophagy in human osteosarcoma U2-OS cells
Wei-Chih Lien, Chung-Hsing Yu, Chia-Yih Wang, Bu-Miin Huang, Ting-Yu Chen, Tzu-Chien Lin, Fu-Chi Kang, Shi-Yuan Sheu, Ta-Shen Kuan J Cell Biochem . 2018 Jun;119(6):4729-4741. doi: 10.1002/jcb.26652.
Human osteosarcoma (bone cancer) is a highly malignant and the most prevalent bone tumor affecting children. Despite recent advances in the understanding of the molecular mechanism by which anticancer drugs kill osteosarcoma or block its growth, however, the mortality rate has declined only modestly. Thus, a new therapeutic approach is needed to be established. 7-hydroxystaurosporine, UCN-01, abrogates the G2 checkpoint thus enhancing the cytotoxicity of chemotherapeutic agents. In addition, it has been evaluated in clinical trials as a single antineoplastic agent in treating several cancers. However, the effects of UCN-01 on treating bone cancer has never been tested. In this study, we found that UCN-01 induced cell cycle arrest and apoptosis in the human osteosarcoma, U2-OS cells. In addition, the migration ability was also reduced, suggesting UCN-01 inhibited cell growth and migration. When U2-OS cells were treated with UCN-01, DNA damage response was triggered. The ataxia telangiectasia mutated (ATM) and the non-canonical downstream effector, ERK, was activated by UCN-01. In addition, depletion of ATM or inhibition of ERK deteriorated the cell viability in UCN-01-treated U2-OS cells. Furthermore, UCN-01 induced autophagy activation for protecting cells from apoptosis. Thus, UCN-01 might function as a single antineoplastic agent in treating human osteosarcoma.
2. UCN-01 and UCN-02, new selective inhibitors of protein kinase C. I. Screening, producing organism and fermentation
T Tamaoki, H Nakano, I Kawamoto, I Takahashi, K Asano J Antibiot (Tokyo) . 1989 Apr;42(4):564-70. doi: 10.7164/antibiotics.42.564.
In the course of continued screening program for new selective inhibitors of protein kinase C (PKC), fermentation broths from over 5,000 soil isolates were screened for their inhibitory activity of PKC. HPLC analysis of active cultures revealed that five different strains (N-71, N-115, N-126, N-128 and N-139) of Streptomyces isolated from various local soil samples were found to produce staurosporine and related compounds. Of these strains, N-126, a high producing strain, was found to produce new selective inhibitors of PKC, UCN-01 and its stereoisomer, UCN-02. The pH control of fermentation resulted in an increase of the production of UCN-01 and UCN-02.
3. UCN-01-mediated G1 arrest in normal but not tumor breast cells is pRb-dependent and p53-independent
M Lowe, K Keyomarsi, X Chen Oncogene . 1999 Oct 7;18(41):5691-702. doi: 10.1038/sj.onc.1202948.
In this study we investigated the growth inhibitory effects of UCN-01 in several normal and tumor-derived human breast epithelial cells. We found that while normal mammary epithelial cells w were very sensitive to UCN-01 with an IC(50) of 10nM tumor cells displayed little to no inhibition of growth with any measurable IC(50) at low UCN-01 concentrations (i.e. 0-80 nM). The UCN-01 treated normal cells arrested in G1 phase and displayed decreased expression of most key cell cycle regulators examined, resulting in inhibition of CDK2 activity due to increased binding of p27 to CDK2. Tumor cells on the other hand displayed no change in any cell cycle distribution or expression of cell cycle regulators. Examination of E6- and E7-derived strains of normal cells revealed that pRb and not p53 function is essential for UCN-01-mediated G1 arrest. Lastly, treatment of normal and tumor cells with high doses of UCN-01 (i.e. 300 nM) revealed a necessary role for a functional G1 checkpoint in mediating growth arrest. Normal cells, which have a functional G1 checkpoint, always arrest in G1 even at very high concentrations of UCN-01. Tumor cells on the other hand have a defective G1 checkpoint and only arrest in S phase with high concentrations of UCN-01. The effect of UCN-01 on the cell cycle is thus quite different from staurosporine, a structural analogue of UCN-01, which arrests normal cells in both G1 and G2, while tumor cells arrest only in the G2 phase of the cell cycle. Our results show the different sensitivity to UCN-01 of normal compared to tumor cells is dependent on a functional pRb and a regulated G1 checkpoint.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
