Diazepinomicin

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 206008

CAS#: 733035-26-2

Description: Diazepinomicin, also known as TLN-4601, is a small-molecule inhibitor of the RAS/RAF/MAPK signaling pathway with potential antineoplastic activity. Diazepinomicin binds to and inhibits Ras kinase, thereby preventing the phosphorylation and activation of proteins downstream of the Ras signal transduction pathway, including serine/threonine kinase RAF (BRAF) and extracellular signal-regulated kinases 1 and 2 (ERK1 and ERK-2). This agent also selectively binds to the peripheral benzodiazepine receptor (PBR), a receptor highly expressed in certain tumor cell types cells, inducing cell cycle arrest and apoptosis in PBR-expressing cells. Diazepinomicin can cross the blood-brain barrier (BBB).


Price and Availability

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Diazepinomicin is not in stock, but may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 206008
Name: Diazepinomicin
CAS#: 733035-26-2
Chemical Formula: C28H34N2O4
Exact Mass: 462.25186
Molecular Weight: 462.58
Elemental Analysis: C, 72.70; H, 7.41; N, 6.06; O, 13.83


Synonym: ECO 4601; ECO-4601;ECO4601;ECO 04601;TLN4601; TLN 4601; TLN-4601; BU 4664L; Diazepinomicin.

IUPAC/Chemical Name: 4,6,8-trihydroxy-10-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)-5H-dibenzo[b,e][1,4]diazepin-11(10H)-one

InChi Key: SALVHVNECODMJP-GNUCVDFRSA-N

InChi Code: InChI=1S/C28H34N2O4/c1-18(2)8-5-9-19(3)10-6-11-20(4)14-15-30-23-16-21(31)17-25(33)27(23)29-26-22(28(30)34)12-7-13-24(26)32/h7-8,10,12-14,16-17,29,31-33H,5-6,9,11,15H2,1-4H3/b19-10+,20-14+

SMILES Code: O=C1C2=CC=CC(O)=C2NC3=C(O)C=C(O)C=C3N1C/C=C(C)/CC/C=C(C)/CC/C=C(C)\C


Technical Data

Appearance:
Solid powder

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:
Soluble in DMSO, not in water

Shelf Life:
>5 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


Additional Information

  
 
 
 


References

1: Abdelmohsen UR, Szesny M, Othman EM, Schirmeister T, Grond S, Stopper H, Hentschel U. Antioxidant and anti-protease activities of diazepinomicin from the sponge-associated Micromonospora strain RV115. Mar Drugs. 2012 Oct;10(10):2208-21. doi: 10.3390/md10102208. Epub 2012 Oct 8. PubMed PMID: 23170078; PubMed Central PMCID: PMC3497017.

2: Mason WP, Belanger K, Nicholas G, Vallières I, Mathieu D, Kavan P, Desjardins A, Omuro A, Reymond D. A phase II study of the Ras-MAPK signaling pathway inhibitor TLN-4601 in patients with glioblastoma at first progression. J Neurooncol. 2012 Apr;107(2):343-9. doi: 10.1007/s11060-011-0747-6. Epub 2011 Nov 3. PubMed PMID: 22048878.

3: Campbell PM, Boufaied N, Fiordalisi JJ, Cox AD, Falardeau P, Der CJ, Gourdeau H. TLN-4601 suppresses growth and induces apoptosis of pancreatic carcinoma cells through inhibition of Ras-ERK MAPK signaling. J Mol Signal. 2010 Nov 2;5:18. doi: 10.1186/1750-2187-5-18. PubMed PMID: 21044336; PubMed Central PMCID: PMC2990749.

4: Bertomeu T, Zvereff V, Ibrahim A, Zehntner SP, Aliaga A, Rosa-Neto P, Bedell BJ, Falardeau P, Gourdeau H. TLN-4601 peripheral benzodiazepine receptor (PBR/TSPO) binding properties do not mediate apoptosis but confer tumor-specific accumulation. Biochem Pharmacol. 2010 Nov 15;80(10):1572-9. doi: 10.1016/j.bcp.2010.07.018. Epub 2010 Jul 22. PubMed PMID: 20655882.

5: Boufaied N, Wioland MA, Falardeau P, Gourdeau H. TLN-4601, a novel anticancer agent, inhibits Ras signaling post Ras prenylation and before MEK activation. Anticancer Drugs. 2010 Jun;21(5):543-52. doi: 10.1097/CAD.0b013e328337f373. PubMed PMID: 20220516.

6: Ratnayake AS, Janso JE, Feng X, Schlingmann G, Goljer I, Carter GT. Evaluating indole-related derivatives as precursors in the directed biosynthesis of diazepinomicin analogues. J Nat Prod. 2009 Mar 27;72(3):496-9. doi: 10.1021/np800664u. PubMed PMID: 19199816.

7: Feng X, Ratnayake AS, Charan RD, Janso JE, Bernan VS, Schlingmann G, He H, Tischler M, Koehn FE, Carter GT. Probing natural product biosynthetic pathways using Fourier transform ion cyclotron resonance mass spectrometry. Bioorg Med Chem. 2009 Mar 15;17(6):2154-61. doi: 10.1016/j.bmc.2008.10.073. Epub 2008 Nov 5. PubMed PMID: 19028101.

8: McAlpine JB, Banskota AH, Charan RD, Schlingmann G, Zazopoulos E, Piraee M, Janso J, Bernan VS, Aouidate M, Farnet CM, Feng X, Zhao Z, Carter GT. Biosynthesis of diazepinomicin/ECO-4601, a Micromonospora secondary metabolite with a novel ring system. J Nat Prod. 2008 Sep;71(9):1585-90. doi: 10.1021/np800376n. Epub 2008 Aug 23. PubMed PMID: 18722414.

9: Gourdeau H, McAlpine JB, Ranger M, Simard B, Berger F, Beaudry F, Farnet CM, Falardeau P. Identification, characterization and potent antitumor activity of ECO-4601, a novel peripheral benzodiazepine receptor ligand. Cancer Chemother Pharmacol. 2008 May;61(6):911-21. Epub 2007 Jul 11. Erratum in: Cancer Chemother Pharmacol. 2009 Feb;63(3):569. Cancer Chemother Pharmacol. 2008 Oct 22. doi: 10.1007/s00280-008-0848-x. Farnet, Chris M [added]. PubMed PMID: 17622531.

10: Charan RD, Schlingmann G, Janso J, Bernan V, Feng X, Carter GT. Diazepinomicin, a new antimicrobial alkaloid from a marine Micromonospora sp. J Nat Prod. 2004 Aug;67(8):1431-3. PubMed PMID: 15332871.