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1、PharmaMars Kahalalide F, Phase II Trials for the Treatment of Severe PsoriasisMADRID, October 28 /PRNewswire/ - PharmaMar today announced that Kahalalide F (KF), its marine-origin compound, has entered into Phase II trials for the treatment of patients with severe psoriasis.KF is currently undergoin
2、g Phase II clinical trials in various tumours: melanoma, non-small lung cancer and hepatocarcinoma.During the Phase I clinical trials on oncological patients treated with KF, it was found that the compound had clinical potential to treat severe psoriasis. These signs of activity, together with the p
3、roducts excellent safety profile, led to the initiation of the clinical development of KF for psoriasis, thereby widening the range of therapeutic applications for this compound beyond the field of oncology.Regulatory authorities have approved the commencement of Phase II studies on patients with ps
4、oriasis, which will be undertaken in hospitals in both Spain and France.This is not the first compound with anti-proliferative activity to show both anti-tumoural and anti-psoriatic activity: methotrexate is a clear example of such dual usage.Approximately 100 million people worldwide suffer from ps
5、oriasis, a chronic, non-contagious inflammation of the skin, characterised by reddish plaques and patches with scales. It affects all ages, but it is most prominent among adults (it is equally common among men and women). The disease is difficult to treat and impairs patients quality of life.Comment
6、ing on the announcement, Isabel Lozano, CEO of PharmaMar, said: PharmaMar continues to focus on advancing cancer care, however where it makes sense to widen the range of therapeutic applications for our compounds, we will explore the opportunity.Notes to editorsKahalalide FKahalalide F is one of a f
7、amily of novel peptides isolated from the Hawaiian mollusk, Elysia rufescens. It is currently in Phase II trials for hepatocarcinoma.PharmaMarPharmaMar is a biopharmaceutical company, advancing cancer care through the discovery and development of innovative marine-derived medicines. PharmaMars clini
8、cal portfolio currently includes Yondelis (TM) in phase II clinical trials (co-developed with Johnson Aplidin(R), in phase II, designated Orphan Drug for acute lymphoblastic leukaemia in 2003; Kahalalide F in phase II and ES-285 in phase I clinical trials.PharmaMar, based in Madrid, Spain, is a subs
9、idiary of the Zeltia Group (Spanish stock exchange: ZEL.MC; Bloomberg: ZEL SM; Reuters: ZEL.MC). PharmaMar can be found on the Web athttp:/Distributed by PR Newswire on behalf of Zeltia Group简介Title: Kahalalide FCAS Registry Number: 149204-42-2Manufacturers Codes: PM-92102Molecular Formula: C75H124N
10、14O16Molecular Weight: 1477.87Percent Composition: C 60.95%, H 8.46%, N 13.27%, O 17.32%Literature References: One of a family of cyclic depsipeptides isolated from the Hawaiian marine mollusk, Elysia rufescens. First reported diet-derived chemical defense peptide; production of which depends on con
11、sumption of the green alga, Bryopsis sp. Isoln: P. J. Schauer et al., EP 610078 (1994 to Pharma Mar); M. T. Hamann, P. J. Scheuer, J. Am. Chem. Soc. 115, 5825 (1993); of the family: M. T. Hamann et al., J. Org. Chem. 61, 6594 (1996). Synthesis: A. Lpez-Maci et al., J. Am. Chem. Soc. 123, 11398 (2001
12、). Stereochemistry: G. Goetz et al., Tetrahedron 55, 7739 (1999). Updated stereochemistry: I. Bonnard et al., J. Nat. Prod.66, 1466 (2003). Identification as defensive peptide: M. A. Becerro et al., J. Chem. Ecol. 27, 2287 (2001). LC/MS/MS determ in plasma: E. Stokvis et al., J. Mass Spectrom. 37, 9
13、92 (2002). Toxicology: A. P. Brown et al., Cancer Chemother. Pharmacol. 50, 333 (2002). In vitro cytotoxic activity: Y. Surez et al., Mol. Cancer Ther. 2, 863 (2003). Mechanism of cytotoxicity: J. M. Sewell et al., Eur. J. Cancer 41, 1637 (2005). Clinical pharmacology in prostate cancer: J. M. Radem
14、aker-Lakhai et al., Clin. Cancer Res.11, 1854 (2005). Review of development and therapeutic potential: M. T. Hamann, Curr. Opin. Mol. Ther. 6, 657-665 (2004).Properties: White amorphous powder. D -8 (c = 4.32 in CH3OH). LD50 in male, female rats (g/kg): 375, 600 i.v. (Brown).Optical Rotation: D -8 (
15、c = 4.32 in CH3OH)Toxicity data: LD50 in male, female rats (g/kg): 375, 600 i.v. (Brown)Therap-Cat: Antineoplastic.Keywords: Antineoplastic; Alkaloids/Natural Products.The antitumoral compound Kahalalide 作用机理The primary mechanism of action of KF has not been identified yet, although multiple targets
16、 have been found and each is a membrane-associated event that may be related to the hydrophobic nature of the compound. COMPARE analysis was negative (9)suggesting that KF has a novel mechanism of action. A cell cycle block in G0-G1 has been determined in a variety of tumor cell lines that include prostate (DU145), cervical (HeLa), colon (HT29), and head and neck (HN30). Earlier in vitro studies identified some mechanisms of action. Cells exposed to b
