MedKoo Cat#: 201630 Name: Karenitecin (Cositecan) CAS#: 203923-89-1 Chemical Formula: C25H28N2O4Si Exact Mass: 448.18183 Molecular Weight: 448.59 Elemental Analysis: C, 66.94; H, 6.29; N, 6.24; O, 14.27; Si, 6.26

Synonym: MCC 12824, MCC-12824, MCC12824, DB 172, DB172, DB-172; BNP 1350, BNP1350, BNP-1350, Karenitecin; Cositecan, 7-Trimethylsilylethylcamptothecin

IUPAC/Chemical Name: (S)-4-ethyl-4-hydroxy-11-(2-(trimethylsilyl)ethyl)-1H-pyrano[3,4:6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione.

InChi Key: POADTFBBIXOWFJ-VWLOTQADSA-N

InChi Code: InChI=1S/C25H28N2O4Si/c1-5-25(30)19-12-21-22-17(13-27(21)23(28)18(19)14-31-24(25)29)15(10-11-32(2,3)4)16-8-6-7-9-20(16)26-22/h6-9,12,30H,5,10-11,13-14H2,1-4H3/t25-/m0/s1

SMILES Code: O=C1[C@](O)(CC)C2=C(CO1)C(N3CC4=C(CC[Si](C)(C)C)C5=CC=CC=C5N=C4C3=C2)=O

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: >2 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

     BioNumerik is currently developing Karenitecin® (also known as BNP1350) as an investigational new anti-tumor drug in the camptothecin class of chemotherapy drugs.  Karenitecin is  currently in an international Phase III clinical trial for  advanced ovarian cancer patients. Karenitecin has the potential for fewer side-effects, improved efficacy, less susceptibility to drug resistance mechanisms and an improved safety profile compared to the currently marketed camptothecin drugs. Based on prior studies, Karenitecin has a lower incidence of severe diarrhea than that caused by the marketed camptothecin drug irinotecan (Camptosar®, Pfizer), and a lower incidence and severity of anemia, neutropenia and thrombocytopenia than that caused by the marketed camptothecin drug topotecan (Hycamtin®, GlaxoSmithKline). Irinotecan and topotecan, the only FDA-approved camptothecins, are used for the treatment of patients with colorectal, small cell lung, ovarian and cervical cancers. Karenitecin® may have the some advantages over these drugs. For detail, please see BioNumerik \'s website.      

References

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2: Daud AI, Dawson J, DeConti RC, Bicaku E, Marchion D, Bastien S, Hausheer FA 3rd, Lush R, Neuger A, Sullivan DM, Munster PN. Potentiation of a topoisomerase I inhibitor, karenitecin, by the histone deacetylase inhibitor valproic acid in melanoma: translational and phase I/II clinical trial. Clin Cancer Res. 2009 Apr 1;15(7):2479-87. doi: 10.1158/1078-0432.CCR-08-1931. Epub 2009 Mar 24. PubMed PMID: 19318485.

3: Grossman SA, Carson KA, Phuphanich S, Batchelor T, Peereboom D, Nabors LB, Lesser G, Hausheer F, Supko JG; New Approaches to Brain Tumor Therapy CNS Consortium. Phase I and pharmacokinetic study of karenitecin in patients with recurrent malignant gliomas. Neuro Oncol. 2008 Aug;10(4):608-16. doi: 10.1215/15228517-2008-030. Epub 2008 Jun 24. PubMed PMID: 18577560; PubMed Central PMCID: PMC2666235.

4: Kavanagh JJ, Sill MW, Ramirez PT, Warshal D, Pearl ML, Morgan MA. Phase II multicenter open-label study of karenitecin in previously treated epithelial ovarian and primary peritoneal cancer: a Gynecologic Oncology Group Study. Int J Gynecol Cancer. 2008 May-Jun;18(3):460-4. Epub 2007 Sep 13. PubMed PMID: 17854432.

5: Jacob E, Scorsone K, Blaney SM, D\'Argenio DZ, Berg SL. Synergy of karenitecin and mafosfamide in pediatric leukemia, medulloblastoma, and neuroblastoma cell lines. Pediatr Blood Cancer. 2008 Apr;50(4):757-60. PubMed PMID: 17849472; PubMed Central PMCID: PMC2975705.

6: Miller AA, Herndon JE 2nd, Gu L, Green MR; Cancer and Leukemia Group B. Phase II trial of karenitecin in patients with relapsed or refractory non-small cell lung cancer (CALGB 30004). Lung Cancer. 2005 Jun;48(3):399-407. Epub 2005 Jan 23. PubMed PMID: 15893009.

7: Daud A, Valkov N, Centeno B, Derderian J, Sullivan P, Munster P, Urbas P, Deconti RC, Berghorn E, Liu Z, Hausheer F, Sullivan D. Phase II trial of karenitecin in patients with malignant melanoma: clinical and translational study. Clin Cancer Res. 2005 Apr 15;11(8):3009-16. PubMed PMID: 15837755.

8: Smith JA, Newman RA, Hausheer FH, Madden T. Evaluation of in vitro drug interactions with karenitecin, a novel, highly lipophilic camptothecin derivative in phase II clinical development. J Clin Pharmacol. 2003 Sep;43(9):1008-14. PubMed PMID: 12971034.

9: Smith JA, Hausheer F, Newman RA, Madden TL. Development of a high-performance liquid chromatographic method to determine the concentration of karenitecin, a novel highly lipophilic camptothecin derivative, in human plasma and urine. J Chromatogr B Biomed Sci Appl. 2001 Aug 5;759(1):117-24. PubMed PMID: 11499615.

10: Matsui S, Endo W, Wrzosek C, Haridas K, Seetharamulu P, Hausheer FH, Rustum YM. Characterisation of a synergistic interaction between a thymidylate synthase inhibitor, ZD1694, and a novel lipophilic topoisomerase I inhibitor karenitecin, BNP1100: mechanisms and clinical implications. Eur J Cancer. 1999 Jun;35(6):984-93. PubMed PMID: 10533483.