GEM-231(GEM-231) - 药物靶点：PKA_专利_临床

概要

基本信息

药物类型

反义寡核苷酸

别名

+ [2]

靶点

PKA

作用机制

Protein kinase A (PKA) family inhibitors

治疗领域

肿瘤

在研适应症-

非在研适应症

肿瘤实体瘤

原研机构

Idera Pharmaceuticals, Inc.

在研机构-

非在研机构

Idera Pharmaceuticals, Inc.

Idera, Inc.

National Cancer Institute

最高研发阶段终止临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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序列信息

Sequence Code 30000502

关联

2

项与 GEM-231 相关的临床试验

NCT00004863 / Completed临床1期IIT

A Phase I Open-Label Safety Study of Escalating Doses of Taxol in Combination With Escalating Doses of GEM231 in Patients With Refractory Solid Tumors

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.
PURPOSE: Phase I trial to study the effectiveness of paclitaxel and GEM 231 in treating patients who have recurrent or refractory solid tumors.

开始日期1999-07-01

申办/合作机构

Montefiore Medical Center

[+1]

NCT00004864 / Completed临床1期IIT

A Phase I Open-Label Safety Study of Escalating Doses of Taxotere in Combination With Escalating Doses of GEM231 in Patients With Refractory Solid Tumors

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Gene therapy such as GEM 231 may inhibit the growth of cancer cells and make the tumor more sensitive to chemotherapy.
PURPOSE: Phase I trial to study the effectiveness of combining docetaxel and GEM 231 in treating patients who have recurrent or refractory solid tumors.

开始日期1999-07-01

申办/合作机构

Montefiore Medical Center

[+1]

100 项与 GEM-231 相关的临床结果

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100 项与 GEM-231 相关的转化医学

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100 项与 GEM-231 相关的专利（医药）

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16

项与 GEM-231 相关的文献（医药）

2011-02-15·International Journal of Cancer1区 · 医学

PKA knockdown enhances cell killing in response to radiation and androgen deprivation

1区 · 医学

Article

作者: Radka Stoyanova ; Zhaomei Mu ; Paul Hachem ; Jean Michel Hannoun-Levi ; Sudhir Agrawal ; Harvey H. Hensley ; Li Yan Khor ; Alan Pollack

AbstractThe therapeutic efficacy of Gem®231, a second generation antisense molecule targeted to the RIα subunit of PKARIα (AS‐PKA), administered in combination with androgen deprivation (AD) and radiation therapy (RT), was examined in androgen sensitive (LNCaP) and insensitive (PC3) cell lines. Apoptosis was assayed by Caspase 3 + 7 activity and Annexin V binding. AS‐PKA significantly increased apoptosis in vitro from RT (both lines), with further increases in LNCaP cells grown in AD medium. In LNCaP cells, AD increased phosphorylated mitogen activated protein‐kinase (pMAPK), which was reduced by AS‐PKA relative to the mismatch (MM) controls. AS‐PKA also reduced pMAPK levels in PC3 cells. Cell death was measured by clonogenic survival assays. In vivo, LNCaP cells were grown orthotopically in nude mice. Tumor kinetics were measured by magnetic resonance imaging and serum prostate‐specific antigen. PC3 cells were grown subcutaneously and tumor volume assessed by caliper measurements. In PC3 xenografts, AS‐PKA caused a significant increase in tumor doubling time relative to MM controls as a monotherapy or in combination with RT. In orthotopic LNCaP tumors, AS‐PKA was ineffective as a monotherapy; however, it caused a statistically significant increase in tumor doubling time relative to MM controls when used in combination with AD, with or without RT. PKARIα levels in tumors were quantified via immunohistochemical (IHC) staining and image analysis. IHC measurements in LNCaP cells exhibited that AS‐PKA reduced PKARIα levels in vivo. We demonstrate for the first time that AS‐PKA enhances cell killing androgen sensitive prostate cancer cells to AD ± RT and androgen insensitive cells to RT.

2006-11-01·Methods and findings in experimental and clinical pharmacology

Gateways to clinical trials.

Article

作者: Bayes, M ; Prous, J R ; Rabasseda, X

5-Methyltetrahydrofolate, (R)-flurbiprofen; Ad5CMV-p53, adalimumab, alefacept, alemtuzumab, Alequel, alicaforsen sodium, almotriptan, anakinra, aprepitant, aripiprazole, armodafinil; Bevacizumab, bortezomib, bosentan; Canfosfamide hydrochloride, ciclesonide, clofarabine, Cypher; Darbepoetin alfa, diclofenac potassium, drotrecogin alfa (activated), duloxetine hydrochloride; Eel calcitonin, eletriptan, eplerenone, everolimus, ezetimibe; Frovatriptan; Gefitinib, gamma-hydroxybutyrate sodium; HKI-272, HYB-165; Ibutamoren mesylate, imatinib mesylate, interleukin-21, ixabepilone; KRN-951; L-Arginine hydrochloride, levodopa/carbidopa/entacapone; Micafungin sodium, motexafin gadolinium, mycophenolic acid sodium salt; Nesiritide; Peginterferon alfa-2a, pitavastatin calcium, pralatrexate, pregabalin, pVAX/L523S-Ad.L523S; Rasagiline mesylate, recombinant human nerve growth factor, regadenoson, rF-PSA, rimonabant, rizatriptan, rofecoxib, rosuvastatin calcium, rV-B7.1, rV-PSA; Sipuleucel-T, sirolimus-eluting stent, solifenacin succinate, sorafenib, sunitinib malate; Talactoferrin alfa, Taxus, tegaserod maleate, teriparatide, tipifarnib; Valdecoxib, vandetanib, vatalanib succinate; WT1-peptide vaccine; Xaliproden hydrochloride. (c) 2006 Prous Science. All rights reserved.

2006-03-01·Investigational New Drugs3区 · 医学

A phase I safety and dose escalation trial of docetaxel combined with GEM®231, a second generation antisense oligonucleotide targeting protein kinase A R1α in patients with advanced solid cancers

3区 · 医学

Article

作者: Manuel Macapinlac ; Mark Einstein ; Benny Wong ; Sanjay Goel ; Sridhar Mani ; Gary Goldberg ; Kavita Desai ; Fabio Volterra ; Russell Martin ; Abbie Fields ; Scott Wadler

PURPOSEGEM231 is a second-generation antisense oligonucleotide targeting the mRNA of the R1alpha regulatory subunit of cAMP dependent protein kinase A. Preclinical studies have demonstrated synergistic antitumor activity when GEM231 is combined with docetaxel. This trial assesses the safety of this combination.EXPERIMENTAL DESIGNDocetaxel was administered once every three weeks (one-cycle) at doses between 50-75 mg/m2. GEM231 was administered twice weekly at 220 mg/m2 for 3 (schedule-A), or 2 (schedule-B) weeks.RESULTSTwenty patients with chemotherapy-refractory advanced cancer received a total of 39 cycles of therapy. Six patients in schedule-A received docetaxel 50 mg/m2, and 14 patients in schedule-B received docetaxel 50-75 mg/m2. In schedule-A, 2 of 6 patients developed cycle-1 dose limiting toxicity (DLT)-grade-3 fatigue or grade-3 serum transaminase elevation. In schedule-B, 1 of 4 patients developed cycle-1 DLT at the highest dose of docetaxel tested (75 mg/m2)--grade-3 febrile neutropenia. Subsequent dose escalations were not pursued since the overall incidence of grade-3 toxicities (including those that occurred after cycle 1) was 75%, and this dose was close to the single agent MTD of docetaxel. Grade-3 toxicities included fatigue (2 patients), transaminase elevation (4 patients), and altered mentation (1 patient). The mean post-infusion aPTT was significantly higher than the pre-infusion value [14.8 seconds; p<0.001]; however, there were no hemorrhagic episodes.CONCLUSIONSThe recommended dose for further development of the combination of docetaxel and GEM231 is 75 mg/m2 and 220 mg/m2, respectively. It is important to administer GEM231 twice weekly for 2 consecutive weeks followed by a one-week break.

100 项与 GEM-231 相关的药物交易

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