更新于：2024-11-04

Antisoma Research Ltd.

子公司|

United Kingdom

子公司|

United Kingdom

更新于：2024-11-04

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项与 Antisoma Research Ltd. 相关的临床试验

NCT01066494 / Unknown status临床2期

A Phase IIa Pharmacokinetic and Efficacy Study of Amonafide L-malate (AS1413) in Combination With Cytarabine in Adult Patients With Acute Myeloid Leukemia (AML)

A phase IIa study to evaluate the pharmacokinetic and efficacy of amonafide L-malate (AS1413) in combination with cytarabine in treating patients with acute myeloid leukemia (AML)

开始日期2010-01-01

申办/合作机构

Antisoma Research Ltd.

NCT01034410 / Terminated临床2期

An Open-label Randomized Controlled Phase II Study of AS1411 Combined With Cytarabine in the Treatment of Patients With Primary Refractory or Relapsed Acute Myeloid Leukemia

This is an open label randomized controlled phase II study of AS1411 combined with Cytarabine in the treatment of patients with primary refractory or relapsed acute myeloid leukemia.

开始日期2010-01-01

申办/合作机构

Antisoma Research Ltd.

EUCTR2007-004427-38-GB / Not yet recruitingN/A

Phase 3 Open-Label Randomized Study of Amonafide L-Malate in Combination withCytarabine Compared to Daunorubicin in Combination with Cytarabine in Patients with Secondary Acute Myeloid Leukemia (AML) - ACCEDE

开始日期2009-07-17

申办/合作机构

Antisoma Research Ltd.

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0 项与 Antisoma Research Ltd. 相关的专利（医药）

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项与 Antisoma Research Ltd. 相关的文献（医药）

2009-06-01·Investigative ophthalmology & visual science2区 · 医学

Transient Retinal Effects of 5,6-Dimethylxanthenone-4-acetic Acid (DMXAA, ASA404), an Antitumor Vascular-Disrupting Agent in Phase I Clinical Trials

2区 · 医学

ArticleOA

作者: Baguley, Bruce C. ; McKeage, Mark J. ; Hogg, Christopher R. ; Acton, Gary ; Thompson, Paul I. ; Jeffery, Mark ; Waller, Susan ; Sharp, Dianne M. ; Green, Colin ; Sissingh, Jennifer I. ; Jameson, Michael B.

PURPOSE:

5,6-Dimethylxanthenone-4-acetic acid (DMXAA), an anticancer vascular-disrupting agent, has induced transient visual symptoms in some patients. Exploratory investigations were undertaken to characterize the visual disturbances in two consecutive phase I trials.

METHODS:

Assessments were made in 21 patients before and immediately after a 20-minute IV infusion of DMXAA, including visual acuity, funduscopy, color discrimination, pattern electroretinography (PERG), pattern visual-evoked potentials (VEP), and full-field electroretinography (ERG). Evaluation of late effects was undertaken subsequently in 12 patients before and after 6 weeks of IV DMXAA at one dose per week.

RESULTS:

Frequency and intensity of transient visual disturbance increased with DMXAA dose, occurring in two thirds of patients at 3000 mg x m(-2). Symptoms included blurring, flickering, fragmentation, alteration of colors, and contrast and mild photosensitivity, starting during the infusion and resolving completely, usually within 60 minutes. Visual acuity was unchanged but color discrimination was perturbed. Dose-dependent increases in PERG P50 implicit time by up to 23 ms returned toward baseline values within 90 minutes. Prominent transient changes on ERG included prolonged scotopic rod and 30-Hz flicker implicit times and reduced 30-Hz flicker amplitude. In the second trial, no clinically significant sustained effects were detected, although an increase in bright flash a-wave implicit time (P = 0.022) was seen on whole-group analysis. In vitro studies showed nonspecific phosphodiesterase inhibition by DMXAA.

CONCLUSIONS:

DMXAA induced acute, transient disturbance of retinal activity consistent with phosphodiesterase inhibition. No clinically significant cumulative effects were noted and most effects occurred at doses higher than those used in ongoing clinical trials (ClinicalTrials.gov numbers, NCT00856336, NCT00863733, and NCT00003697).

2008-04-01·Cancer research1区 · 医学

The Nucleolin Targeting Aptamer AS1411 Destabilizes Bcl-2 Messenger RNA in Human Breast Cancer Cells

1区 · 医学

Article

作者: Soundararajan, Sridharan ; Courtenay-Luck, Nigel ; Spicer, Eleanor K. ; Chen, Weiwei ; Fernandes, Daniel J.

Abstract:

We sought to determine whether nucleolin, a bcl-2 mRNA-binding protein, has a role in the regulation of bcl-2 mRNA stability in MCF-7 and MDA-MB-231 breast cancer cells. Furthermore, we examined the efficacy of the aptamer AS1411 in targeting nucleolin and inducing bcl-2 mRNA instability and cytotoxicity in these cells. AS1411 at 5 μmol/L inhibited the growth of MCF-7 and MDA-MB-231 cells, whereas 20 μmol/L AS1411 had no effect on the growth rate or viability of normal MCF-10A mammary epithelial cells. This selectivity of AS1411 was related to a greater uptake of AS1411 into the cytoplasm of MCF-7 cells compared with MCF-10A cells and to a 4-fold higher level of cytoplasmic nucleolin in MCF-7 cells. Stable siRNA knockdown of nucleolin in MCF-7 cells reduced nucleolin and bcl-2 protein levels and decreased the half-life of bcl-2 mRNA from 11 to 5 hours. Similarly, AS1411 (10 μmol/L) decreased the half-life of bcl-2 mRNA in MCF-7 and MDA-MB-231 cells to 1.0 and 1.2 hours, respectively. In contrast, AS1411 had no effect on the stability of bcl-2 mRNA in normal MCF-10A cells. AS1411 also inhibited the binding of nucleolin to the instability element AU-rich element 1 of bcl-2 mRNA in a cell-free system and in MCF-7 cells. Together, the results suggest that AS1411 acts as a molecular decoy by competing with bcl-2 mRNA for binding to cytoplasmic nucleolin in these breast cancer cell lines. This interferes with the stabilization of bcl-2 mRNA by nucleolin and may be one mechanism by which AS1411 induces tumor cell death. [Cancer Res 2008;68(7):2358–65]

2006-03-15·Clinical cancer research : an official journal of the American Association for Cancer Research1区 · 医学

5,6-Dimethylxanthenone-4-Acetic Acid in the Treatment of Refractory Tumors: a Phase I Safety Study of a Vascular Disrupting Agent

1区 · 医学

Article

作者: Jameson, Michael B. ; Baguley, Bruce C. ; Fong, Peter ; Ravic, Miroslav ; Kestell, Phil ; McKeage, Mark J. ; Jeffery, Mark

Abstract:

This phase I safety study aimed to identify the optimal dose of the vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA) for combination studies. Using a crossover design, 15 patients with refractory tumors were allocated randomly to receive six sequential doses of DMXAA (300, 600, 1,200, 1,800, 2,400, and 3,000 mg m−2), each given once-weekly as a 20-minute i.v. infusion. The drug was generally well tolerated. Transient, moderate increases in the heart rate–corrected cardiac QT interval occurred at the two highest doses. DMXAA produced transient dose-dependent increases in blood pressure. Transient, dose-related visual disturbances occurred at the two highest doses. No significant changes in Ktrans and kep were observed but Ve, a secondary dynamic contrast–enhanced magnetic resonance imaging variable, increased significantly after giving DMXAA. At 1,200 mg m−2, the Cmax and the area under the concentration-time curve over 24 hours for total and free DMXAA plasma concentrations were 315 ± 25.8 μg/mL, 29 ± 6.4 μg/mL·d, 8.0 ± 1.77 μg/mL, and 0.43 ± 0.07 μg/mL·d, respectively. Plasma levels of the vascular damage biomarker 5-hydroxyindoleacetic acid increased in the 4 hours after treatment in a dose-dependent fashion up to 1,200 mg m−2, with a plateau thereafter. Doses in the range of 1,200 mg m−2 have been selected for further studies (phase II combination studies with taxanes and platins are under way) because this dose produced no significant effect on heart rate–corrected cardiac QT interval, produced near maximum levels of 5-hydroxyindoleacetic acid, achieved DMXAA plasma concentrations within the preclinical therapeutic range, and was well tolerated.

项与 Antisoma Research Ltd. 相关的新闻（医药）

2010-05-21

·BioSpace

Antisoma PLC to Present at the Citi Investment Research Global Health Care Conference

LONDON--(Marketwire - May 21, 2010) - 21 May 2010, London, UK, and Cambridge, MA: Antisoma plc (LSE: ASM; USOTC:ATSMY) announces that its CEO, Glyn Edwards, will present at the 2010 Citi Investment Research Global Health Care Conference in New York at 10.30 am local time (3.30 pm BST) on Thursday 27 May. A webcast of the presentation will be available on Antisoma's website at For live viewing of the webcast, it is recommended that viewers log on 15 minutes early in order to register and download any necessary software. Enquiries: Alison Saville Senior Marketing and Communications Executive Antisoma plc +44 (0)20 3249 2144 Background on Antisoma Antisoma is a London Stock Exchange-listed biopharmaceutical company that develops novel products for the treatment of cancer. The Company has operations in the UK and the US. Please visit for further information about Antisoma. [HUG#1417932] Enquiries: Alison Saville Senior Marketing and Communications Executive Antisoma plc +44 (0)20 3249 2144

2007-02-16

·Pharma Times

Antisoma losses narrow, partnership deal soon for AS1404

The UK’s Antisoma says that its half-year operating losses have narrowed 18.8% and is predicting a strong 2007 on the back of progress through the pipeline of a number of drugs. The loss was £7.8 million while revenues for the six months ended December 31 were £300,000, down from £1.3 million in the like, year-earlier period. The company ended the year with cash and equivalents of £33.6 million. Antisoma’s chairman Barry Price said the company had ended the year on a high, most notably after having announced positive data from three Phase II trials of AS1404 in lung, prostate and ovarian cancer. Preparations are being made for a Phase III trial in lung cancer progressing through talks with potential marketing partners for the drug. Dr Price noted that “interest in licensing AS1404 has been considerable and we are confident that we will reach an agreement with a strong partner during the first half of 2007.” Roche, which had first refusal on AS1404 through another licensing deal with Antisoma, chose not to exercise its option to take the drug into Phase III in June, leading to a dramatic fall in the UK firm’s share price. Sanofi-Aventis, AstraZeneca and Pfizer have been rumoured to be interested in a partnership. Regarding the rest of the pipeline, AS1411 is progressing to Phase II trials in renal cancer and acute myeloid leukaemia and a Phase I study shows promising activity in renal cancer. Plans are being made to begin a Phase II trial of the anti-MUC1 antibody drug AS1402 during this year and first trials of the antibody-cytokine drug, AS1409, in melanoma and renal cell carcinoma, should start in 2007. In December, Antisoma raised £26.3 million, before expenses, through an oversubscribed placing of almost 74 million new shares and “the proceeds will enable us to press ahead with the development of our promising pipeline,” Dr Price concluded.

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药物(靶点)	适应症	全球最高研发状态

AS-1411 ( NCL )	复发性急性髓细胞白血病更多	终止
Monoclonal antibody HMFG1(Cancer Research UK) ( MUC1 )	局部晚期乳腺癌更多	终止
氨萘非特马来酸盐 ( DNA x Top II )	急性髓性白血病更多	无进展
AS-1409 ( EDB-FN x IL-12R )	转移性肾细胞癌更多	无进展
伐地美生 ( STING )	转移性去势抵抗性前列腺癌更多	无进展