WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 201020
CAS#: 220997-97-7
Description: Diflomotecan, also known as BN80915, is an E-ring modified camptothecin analogue, which possesses greater lactone stability in plasma compared with other topoisomerase I inhibitors. Diflomotecan is also a 10,11-difluoro-homocamptothecin, represents a new promising class of topoisomerase I inhibitors with enhanced plasma stability and superior preclinical anti-tumour activity as compared to the established camptothecins, irinotecan and topotecan. Diflomotecan was the first homocamptothecin to enter clinical studies. Phase I data are summarized for both the intravenous and oral schedules. The toxicity is primarily haematological while no severe gastrointestinal toxicity has been observed in contrast to other topoisomerase I inhibitors. Diflomotecan has a high oral bioavailability (72 - 95%) and the oral day 1 - 5 every 3 weeks regimen is recommended for Phase II testing because it is relatively well tolerated, convenient and mimics protracted exposure.
MedKoo Cat#: 201020
Name: Diflomotecan
CAS#: 220997-97-7
Chemical Formula: C21H16F2N2O4
Exact Mass: 398.10781
Molecular Weight: 398.35955
Elemental Analysis: C, 63.32; H, 4.05; F, 9.54; N, 7.03; O, 16.07
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Synonym: BN80915; BN-80915; BN 80915; Diflomotecan.
IUPAC/Chemical Name: (R)-5-ethyl-9,10-difluoro-5-hydroxy-4,5-dihydrooxepino[3',4':6,7]indolizino[1,2-b]quinoline-3,15(1H,13H)-dione
InChi Key: LFQCJSBXBZRMTN-OAQYLSRUSA-N
InChi Code: InChI=1S/C21H16F2N2O4/c1-2-21(28)7-18(26)29-9-12-13(21)5-17-19-11(8-25(17)20(12)27)3-10-4-14(22)15(23)6-16(10)24-19/h3-6,28H,2,7-9H2,1H3/t21-/m1/s1
SMILES Code: O=C(OC1)C[C@](O)(CC)C2=C1C(N3CC4=CC5=CC(F)=C(F)C=C5N=C4C3=C2)=O
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 soluble 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).
HS Tariff Code: 2934.99.9001
The following data is based on the product molecular weight 398.35955 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 |
1: Mangas-Sanjuan V, Buil-Bruna N, Garrido MJ, Soto E, Trocóniz IF. Semimechanistic Cell-Cycle Type-Based Pharmacokinetic/Pharmacodynamic Model of Chemotherapy-Induced Neutropenic Effects of Diflomotecan under Different Dosing Schedules. J Pharmacol Exp Ther. 2015 Jul;354(1):55-64. doi: 10.1124/jpet.115.223776. Epub 2015 May 6. PubMed PMID: 25948593.
2: Kroep JR, Gelderblom H. Diflomotecan, a promising homocamptothecin for cancer therapy. Expert Opin Investig Drugs. 2009 Jan;18(1):69-75. doi: 10.1517/13543780802571674 . Review. PubMed PMID: 19053883.
3: Graham JS, Falk S, Samuel LM, Cendros JM, Evans TR. A multi-centre dose-escalation and pharmacokinetic study of diflomotecan in patients with advanced malignancy. Cancer Chemother Pharmacol. 2009 Apr;63(5):945-52. doi: 10.1007/s00280-008-0795-6. Epub 2008 Jul 25. PubMed PMID: 18654747.
4: Liao Z, Robey RW, Guirouilh-Barbat J, To KK, Polgar O, Bates SE, Pommier Y. Reduced expression of DNA topoisomerase I in SF295 human glioblastoma cells selected for resistance to homocamptothecin and diflomotecan. Mol Pharmacol. 2008 Feb;73(2):490-7. Epub 2007 Nov 5. PubMed PMID: 17984197; PubMed Central PMCID: PMC2998068.
5: Scott L, Soepenberg O, Verweij J, de Jonge MJ, Th Planting AS, McGovern D, Principe P, Obach R, Twelves C. A multicentre phase I and pharmacokinetic study of BN80915 (diflomotecan) administered daily as a 20-min intravenous infusion for 5 days every 3 weeks to patients with advanced solid tumours. Ann Oncol. 2007 Mar;18(3):569-75. PubMed PMID: 17322542.
6: Peters R, Althaus M, Diolez C, Rolland A, Manginot E, Veyrat M. Practical formal total syntheses of the homocamptothecin derivative and anticancer agent diflomotecan via asymmetric acetate aldol additions to pyridine ketone substrates. J Org Chem. 2006 Sep 29;71(20):7583-95. PubMed PMID: 16995662.
7: Trocòniz IF, Garrido MJ, Segura C, Cendrós JM, Principe P, Peraire C, Obach R. Phase I dose-finding study and a pharmacokinetic/pharmacodynamic analysis of the neutropenic response of intravenous diflomotecan in patients with advanced malignant tumours. Cancer Chemother Pharmacol. 2006 Jun;57(6):727-35. Epub 2005 Oct 28. PubMed PMID: 16261364.
8: Sparreboom A, Gelderblom H, Marsh S, Ahluwalia R, Obach R, Principe P, Twelves C, Verweij J, McLeod HL. Diflomotecan pharmacokinetics in relation to ABCG2 421C>A genotype. Clin Pharmacol Ther. 2004 Jul;76(1):38-44. PubMed PMID: 15229462.
9: Osheroff N. Diflomotecan. Ipsen. IDrugs. 2004 Mar;7(3):257-63. Review. PubMed PMID: 15011101.
10: Gelderblom H, Salazar R, Verweij J, Pentheroudakis G, de Jonge MJ, Devlin M, van Hooije C, Seguy F, Obach R, Pruñonosa J, Principe P, Twelves C. Phase I pharmacological and bioavailability study of oral diflomotecan (BN80915), a novel E-ring-modified camptothecin analogue in adults with solid tumors. Clin Cancer Res. 2003 Sep 15;9(11):4101-7. PubMed PMID: 14519632.
