UCN-01
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| Category | Antineoplastic |
| Catalog number | BBF-01897 |
| CAS | 112953-11-4 |
| Molecular Weight | 482.53 |
| Molecular Formula | C28H26N4O4 |
| Purity | >99% by HPLC |
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Description
KRX-0601, also known as UCN-01, is a synthetic derivative of staurosporine with antineoplastic activity. It inhibits many phosphokinases, including the serine/threonine kinase AKT, calcium-dependent protein kinase C, and cyclin-dependent kinases. This agent arrests tumor cells in the G1/S of the cell cycle and prevents nucleotide excision repair by inhibiting the G2 checkpoint kinase chk1, resulting apoptosis.
Specification
| Synonyms | Antibiotic UCN 01; UCN01; Staurosporine; 7-hydroxystaurosporine; KW-2401; KW 2401; KW2401; (3R,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; (+)-UCN-01; KRX 0601; NSC 638850 |
| Storage | Store at -20°C |
| IUPAC Name | (2S,3R,4R,6R,18R)-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-HQCWYSJUSA-N |
| Source | Streptomyces sp. |
Properties
| Appearance | Pale Yellow Crystal |
| Application | Antineoplastic Agents |
| Antibiotic Activity Spectrum | Neoplastics (Tumor) |
| Boiling Point | 705.7±60.0°C (Predicted) |
| Melting Point | 314.42°C (Predicted) |
| Density | 1.63±0.1 g/cm3 (Predicted) |
| Solubility | Soluble in Ethanol, Methanol, DMF, DMSO |
Reference Reading
1.Lipopolysaccharide and the glycoside ring of staurosporine induce CD14 expression on bone marrow granulocytes by different mechanisms.
Pedron T;Girard R;Inoue K;Charon D;Chaby R Mol Pharmacol. 1997 Oct;52(4):692-700.
We established previously that lipopolysaccharide (LPS) can induce the expression of LPS-binding sites on bone marrow cells (BMC). We now report that staurosporine (STP), a glycosylated indolocarbazole alkaloid with potent inhibitory activity for various protein kinases, can induce the same effect. With both agents, the newly expressed LPS receptor was found to be CD14. The STP-induced effect was independent of its protein kinase inhibitory activity because several other protein kinase inhibitors, such as the indolocarbazole K-252a, the bisindolylmaleimide RO-31-8220, the perylenequinone calphostin C, and the isoquinolinesulfonamide H7, did not induce CD14 expression. The observation that the STP analog K-252a with an identical polyaromatic aglycon moiety was inactive yet the analog UCN-01 with an identical glycoside ring was active suggests that the induction of CD14 expression is triggered by the sugar moiety of STP. Three lines of evidence show that the mechanism of CD14 expression induced by STP differs from that induced by LPS: (i) unlike LPS, STP can stimulate BMC from LPS-unresponsive C3H/HeJ mice, (ii) LPS and STP effects are additive at a saturating dose of LPS, and (iii) the protein kinase inhibitor K-252a inhibits the LPS-induced but not STP-induced stimulation.
2.Interruption of the Ras/MEK/ERK signaling cascade enhances Chk1 inhibitor-induced DNA damage in vitro and in vivo in human multiple myeloma cells.
Dai Y;Chen S;Pei XY;Almenara JA;Kramer LB;Venditti CA;Dent P;Grant S Blood. 2008 Sep 15;112(6):2439-49. doi: 10.1182/blood-2008-05-159392. Epub 2008 Jul 9.
The role of the Ras/MEK/ERK pathway was examined in relation to DNA damage in human multiple myeloma (MM) cells exposed to Chk1 inhibitors in vitro and in vivo. Exposure of various MM cells to marginally toxic concentrations of the Chk1 inhibitors UCN-01 or Chk1i modestly induced DNA damage, accompanied by Ras and ERK1/2 activation. Interruption of these events by pharmacologic (eg, the farnesyltransferase inhibitor R115777 or the MEK1/2 inhibitor PD184352) or genetic (eg, transfection with dominant-negative Ras or MEK1 shRNA) means induced pronounced DNA damage, reflected by increased gammaH2A.X expression/foci formation and by comet assay. Increased DNA damage preceded extensive apoptosis. Notably, similar phenomena were observed in primary CD138(+) MM cells. Enforced MEK1/2 activation by B-Raf transfection prevented R115777 but not PD184352 from inactivating ERK1/2 and promoting Chk1 inhibitor-induced gammaH2A.X expression. Finally, coadministration of R115777 diminished UCN-01-mediated ERK1/2 activation and markedly potentiated gammaH2A.X expression in a MM xenograft model, associated with a striking increase in tumor cell apoptosis and growth suppression. Such findings suggest that Ras/MEK/ERK activation opposes whereas its inhibition dramatically promotes Chk1 antagonist-mediated DNA damage.
3.UCN-01 (7-hydroxystaurosporine) and other indolocarbazole compounds: a new generation of anti-cancer agents for the new century?
Akinaga S;Sugiyama K;Akiyama T Anticancer Drug Des. 2000 Feb;15(1):43-52.
UCN-01 (7-hydroxystaurosporine) is a protein kinase inhibitor which is under development as an anti-cancer agent in the USA and Japan. Although UCN-01 was originally isolated from the culture broth of Streptomyces sp. as a protein kinase C-selective inhibitor, its ultimate target as an anti-cancer agent remains elusive. As a single agent, UCN-01 exhibits two key biochemical effects, namely accumulation of cells in the G1 phase of the cell cycle and induction of apoptosis. Both these effects may be important for its anti-cancer activity. As a modulator, UCN-01 enhances the cytotoxicity of other anti-cancer drugs such as DNA-damaging agents and anti-metabolite drugs through putative abrogation of G2 and/or S phase accumulation induced by these anti-cancer agents. Currently, in addition to UCN-01, four other indolocarbazole anti-cancer drugs-two protein kinase inhibitors, CGP 41251, CEP-751, and two DNA-damaging agents, NB-506 and a Rebeccamycin analog-are undergoing clinical investigations in the USA, Europe or Japan. In this review, we would like to address the differences and similarities of these indolocarbazole compounds as anti-cancer agents with regard to their mechanism(s) of action, the effects on cell cycle progression, induction of apoptosis and modulation of drug sensitivity.
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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 ╳
