当前位置： SCI文献检索 > INVESTIGATIONAL NEW DRUGS期刊下所有文献 > SHetA2 interference with mortalin binding to p66shc and p53 identified using drug-conjugated magnetic microspheres.

SHetA2 interference with mortalin binding to p66shc and p53 identified using drug-conjugated magnetic microspheres.

Abstract：

:SHetA2 is a small molecule flexible heteroarotinoid (Flex-Het) with promising cancer prevention and therapeutic activity. Extensive preclinical testing documented lack of SHetA2 toxicity at doses 25 to 150 fold above effective doses. Knowledge of the SHetA2 molecular target(s) that mediate(s) the mechanism of SHetA2 action is critical to appropriate design of clinical trials and improved analogs. The aim of this study was to develop a method to identify SHetA2 binding proteins in cancer cells. A known metabolite of SHetA2 that has a hydroxyl group available for attachment was synthesized and conjugated to a linker for attachment to a magnetic microsphere. SHetA2-conjugated magnetic microspheres and unconjugated magnetic microspheres were separately incubated with aliquots of a whole cell protein extract from the A2780 human ovarian cancer cell line. After washing away non-specifically bound proteins with the protein extraction buffer, SHetA2-binding proteins were eluted with an excess of free SHetA2. In two independent experiments, an SDS gel band of about 72 kDa was present at differential levels in wells of eluent from SHetA2-microspheres in comparison to wells of eluent from unconjugated microspheres. Mass spectrometry analysis of the bands (QStar) and straight eluents (Orbitrap) identified mortalin (HSPA9) to be present in the eluent from SHetA2-microspheres and not in eluent from unconjugated microspheres. Co-immunoprecipitation experiments demonstrated that SHetA2 interfered with mortalin binding to p53 and p66 Src homologous-collagen homologue (p66shc) inside cancer cells. Mortalin and SHetA2 conflictingly regulate the same molecules involved in mitochondria-mediated intrinsic apoptosis. The results validate the power of this protocol for revealing drug targets.

journal_name

Invest New Drugs

journal_title

Investigational new drugs

authors

Benbrook DM,Nammalwar B,Long A,Matsumoto H,Singh A,Bunce RA,Berlin KD

doi

10.1007/s10637-013-0041-x

subject

Has Abstract

pub_date

2014-06-01 00:00:00

pages

412-23

issue

3

eissn

0167-6997

issn

1573-0646

journal_volume

32

pub_type

杂志文章

相关文献

INVESTIGATIONAL NEW DRUGS文献大全
  • Different biological effects of the two protein kinase C activators bryostatin-1 and TPA on human carcinoma cell lines.

    abstract：:Bryostatin 1 (Bryo) is a naturally occurring macrocyclic lactone with antineoplastic activity. Like the phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate (TPA) it directly activates the calcium- and phospholipid-dependent protein kinase C (PKC), thus generating a number of different cellular responses. We investigat...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/BF00873230

    authors： Steube KG,Grunicke D,Drexler HG

    更新日期：1994-01-01 00:00:00

  • 9-Aminocamptothecin (9-AC) given as a 120-hour continuous infusion in patients with advanced adenocarcinomas of the stomach and gastroesophageal junction: A phase II trial of the University of Chicago phase II consortium.

    abstract：:9-Aminocamptothecin (9-AC) is a water-insoluble camptothecin derivative that demonstrated broad activity in pre-clinical studies. In vitro, greater anti-tumor efficacy can be achieved with prolonged administration. A minor response was observed in gastric cancer in a phase I study. We conducted a phase II study of 9-A...

    journal_title：Investigational new drugs

    pub_type： 临床试验,杂志文章,多中心研究

    doi：10.1023/B:DRUG.0000026259.28395.c2

    authors： Kindler HL,Avadhani A,Wade-Oliver K,Karrison T,Mani S,Vokes EE

    更新日期：2004-08-01 00:00:00

  • Novel acridine-based agents with topoisomerase II inhibitor activity suppress mesothelioma cell proliferation and induce apoptosis.

    abstract：:Human topoisomerase II (hTopoII) inhibitors are important chemotherapeutic agents in many different settings including treatment of malignant mesothelioma. Topoisomerase poisons, such as etoposide and doxorubicin, function by trapping the DNA-enzyme covalent complex producing DNA strand breaks which can ultimately lea...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-011-9720-7

    authors： Raza A,Jacobson BA,Benoit A,Patel MR,Jay-Dixon J,Hiasa H,Ferguson DM,Kratzke RA

    更新日期：2012-08-01 00:00:00

  • Phase Ia/Ib study of the pan-class I PI3K inhibitor pictilisib (GDC-0941) administered as a single agent in Japanese patients with solid tumors and in combination in Japanese patients with non-squamous non-small cell lung cancer.

    abstract：:Pictilisib (GDC-0941) is an oral class I phosphatidylinositol-3-phosphate kinase inhibitor. This phase Ia/Ib study investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of pictilisib in monotherapy or in combination with carboplatin-paclitaxel and bevacizumab (CP + BEV) in Japanese patients wit...

    journal_title：Investigational new drugs

    pub_type： 杂志文章,多中心研究

    doi：10.1007/s10637-016-0382-3

    authors： Yamamoto N,Fujiwara Y,Tamura K,Kondo S,Iwasa S,Tanabe Y,Horiike A,Yanagitani N,Kitazono S,Inatani M,Tanaka J,Nishio M

    更新日期：2017-02-01 00:00:00

  • Silibinin ameliorates oxidative stress induced aberrant crypt foci and lipid peroxidation in 1, 2 dimethylhydrazine induced rat colon cancer.

    abstract：:Pharmacological intervention to reduce CRC mortality entails the use of oral agents that can avert carcinogenesis. Silibinin, a major component of silymarin isolated from Silybum marianum (L.) was found to possess attractive remedial features. An in vivo study was designed to elucidate the effect of silibinin on the f...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-009-9237-5

    authors： Sangeetha N,Aranganathan S,Nalini N

    更新日期：2010-06-01 00:00:00

  • Posterior reversible encephalopathy syndrome induced by enzalutamide in a patient with castration-resistant prostate cancer.

    abstract：:Posterior reversible encephalopathy syndrome (PRES) is a clinical/radiological syndrome characterized by symptoms that can include seizure, headache, impaired vision and hypertension, and can be confirmed by magnetic resonance imaging. Numerous reports have emerged that describe PRES in cancer patients. The list of me...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-014-0193-3

    authors： Crona DJ,Whang YE

    更新日期：2015-06-01 00:00:00

  • Phase 1 clinical trial of the novel proteasome inhibitor marizomib with the histone deacetylase inhibitor vorinostat in patients with melanoma, pancreatic and lung cancer based on in vitro assessments of the combination.

    abstract：PURPOSE:Combining proteasome and histone deacetylase (HDAC) inhibition has been seen to provide synergistic anti-tumor activity, with complementary effects on a number of signaling pathways. The novel bi-cyclic structure of marizomib with its unique proteasome inhibition, toxicology and efficacy profiles, suggested uti...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-011-9766-6

    authors： Millward M,Price T,Townsend A,Sweeney C,Spencer A,Sukumaran S,Longenecker A,Lee L,Lay A,Sharma G,Gemmill RM,Drabkin HA,Lloyd GK,Neuteboom ST,McConkey DJ,Palladino MA,Spear MA

    更新日期：2012-12-01 00:00:00

  • A phase I study of zibotentan (ZD4054) in patients with metastatic, castrate-resistant prostate cancer.

    abstract：PURPOSE:To assess the maximum well-tolerated dose (MWTD), dose limiting toxicity (DLT), pharmacokinetics (PK) and pharmacodynamics of zibotentan, a novel specific endothelin-A receptor antagonist, in patients with metastatic prostate cancer. METHODS:Patients with metastatic, castrate-resistant prostate cancer (CRPC) w...

    journal_title：Investigational new drugs

    pub_type： 杂志文章,多中心研究

    doi：10.1007/s10637-009-9318-5

    authors： Schelman WR,Liu G,Wilding G,Morris T,Phung D,Dreicer R

    更新日期：2011-02-01 00:00:00

  • Randomized phase II study of three doses of the integrin inhibitor cilengitide versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer.

    abstract：INTRODUCTION:This multicenter, open-label, phase II study was carried out to compare the efficacy and safety of cilengitide (EMD 121974), a selective inhibitor of the cell-surface integrins αVβ3 and αVβ5, with that of docetaxel in patients with advanced non-small-cell lung cancer (NSCLC). METHODS:Patients (n = 140) wi...

    journal_title：Investigational new drugs

    pub_type： 杂志文章,多中心研究,随机对照试验

    doi：10.1007/s10637-012-9842-6

    authors： Manegold C,Vansteenkiste J,Cardenal F,Schuette W,Woll PJ,Ulsperger E,Kerber A,Eckmayr J,von Pawel J

    更新日期：2013-02-01 00:00:00

  • Phase 1/2 study of orteronel (TAK-700), an investigational 17,20-lyase inhibitor, with docetaxel-prednisone in metastatic castration-resistant prostate cancer.

    abstract：BACKGROUND:Docetaxel-prednisone (DP) is an approved therapy for metastatic castration-resistant prostate cancer (mCRPC). Orteronel (TAK-700) is an investigational, selective, non-steroidal inhibitor of 17,20-lyase, a key enzyme in androgenic hormone production. This phase 1/2 study evaluated orteronel plus DP in mCRPC ...

    journal_title：Investigational new drugs

    pub_type： 杂志文章,多中心研究

    doi：10.1007/s10637-014-0199-x

    authors： Petrylak DP,Gandhi JG,Clark WR,Heath E,Lin J,Oh WK,Agus DB,Carthon B,Moran S,Kong N,Suri A,Bargfrede M,Liu G

    更新日期：2015-04-01 00:00:00

  • Population pharmacokinetics and pharmacokinetic-pharmacodynamic relationships for docetaxel.

    abstract：:The population approach has been implemented prospectively in the clinical development of docetaxel (Taxotere). Overall 640 patients were evaluable for the population PK/PD analysis. The PK analysis evidenced significant covariates explaining the inter-patient variability of docetaxel clearance and the PK/PD analysis ...

    journal_title：Investigational new drugs

    pub_type： 杂志文章,评审

    doi：10.1023/a:1010687017717

    authors： Bruno R,Vivier N,Veyrat-Follet C,Montay G,Rhodes GR

    更新日期：2001-05-01 00:00:00

  • A phase II study of bosentan, a dual endothelin receptor antagonist, as monotherapy in patients with stage IV metastatic melanoma.

    abstract：:There is no effective systemic therapy for disseminated metastatic melanoma. Data suggest that endothelin may play a role in pathophysiology of melanoma and that the dual endothelin receptor antagonist bosentan may have anti-tumor activity. This multicenter, open-label, single-arm, prospective, proof-of-concept study ...

    journal_title：Investigational new drugs

    pub_type： 杂志文章,多中心研究

    doi：10.1007/s10637-006-9014-7

    authors： Kefford R,Beith JM,Van Hazel GA,Millward M,Trotter JM,Wyld DK,Kusic R,Shreeniwas R,Morganti A,Ballmer A,Segal E,Nayler O,Clozel M

    更新日期：2007-06-01 00:00:00

  • Phase II trial of menogaril in metastatic adenocarcinoma of the prostate. A Southwest Oncology Group study.

    abstract：:Menogaril, a semisynthetic anthracycline antibiotic, was administered to patients with metastatic adenocarcinoma of the prostate. Forty-five patients with measurable disease and 45 patients with evaluable disease received 150-200 mg/m2 over 1 hour every 28 days. There were three partial responses (PR) among 87 patient...

    journal_title：Investigational new drugs

    pub_type： 临床试验,杂志文章,多中心研究

    doi：10.1007/BF00873240

    authors： Taylor SA,Blumenstein BA,Stephens RL,Crawford ED,Pistone B,Hill JB

    更新日期：1994-01-01 00:00:00

  • Phase I trial of 5-fluorouracil by 24-hour infusion weekly.

    abstract：:A novel schedule of 5-fluorouracil administration has been developed for biochemical modulation studies. In combination with the pyrimidine synthesis inhibitor PALA, 5-fluorouracil has been given as a 24-hour infusion, repeated weekly: a dose of 2600 mg/m2 is well tolerated. To identify a suitable dose of 5-fluorourac...

    journal_title：Investigational new drugs

    pub_type： 临床试验,杂志文章

    doi：10.1007/BF00874152

    authors： Haas NB,Hines JB,Hudes GR,Johnston N,Ozols RF,O'Dwyer PJ

    更新日期：1993-05-01 00:00:00

  • Mitoxantrone in combination with prednimustine in treatment of unfavorable non-Hodgkin lymphoma.

    abstract：:Mitoxantrone (Novantrone) and prednimustine (Sterecyt) are both active as single agents in the treatment of unfavorable non-Hodgkin lymphoma (UNHL). The efficacy and toxicity of the combination of these agents (NOSTE) was evaluated in 28 patients with advanced histopathologically proven UNHL who were not eligible for ...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/BF00195368

    authors： Landys KE

    更新日期：1988-06-01 00:00:00

  • A phase I clinical trial of navitoclax, a targeted high-affinity Bcl-2 family inhibitor, in combination with gemcitabine in patients with solid tumors.

    abstract：PURPOSE:To investigate the safety, optimal dosing, pharmacokinetics and clinical activity of a regimen of navitoclax (ABT-263) combined with gemcitabine in patients with solid tumors. EXPERIMENTAL DESIGN:Patients with solid tumors for which gemcitabine was deemed an appropriate therapy were enrolled into one of two di...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-014-0110-9

    authors： Cleary JM,Lima CM,Hurwitz HI,Montero AJ,Franklin C,Yang J,Graham A,Busman T,Mabry M,Holen K,Shapiro GI,Uronis H

    更新日期：2014-10-01 00:00:00

  • Gilteritinib, a FLT3/AXL inhibitor, shows antileukemic activity in mouse models of FLT3 mutated acute myeloid leukemia.

    abstract：:Advances in the understanding of the molecular basis for acute myeloid leukemia (AML) have generated new potential targets for treatment. Fms-like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in AML and mutations in this gene are associated with poor overall survival. AXL plays a role in the ac...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-017-0470-z

    authors： Mori M,Kaneko N,Ueno Y,Yamada M,Tanaka R,Saito R,Shimada I,Mori K,Kuromitsu S

    更新日期：2017-10-01 00:00:00

  • Phase II feasibility study of high dose epirubicin plus etoposide and cisplatin (HDEEC) regimen in small cell lung cancer.

    abstract：:Seventeen patients with small cell lung cancer entered a phase II trial testing the feasibility of adding high dose epirubicin (100-120 mg/m2, day 1) in combination with etoposide (60-80 mg/m2, days 1-5) and cisplatin (70 mg/m2, day 1) courses repeated every three weeks. Complete responders received thoracic (40 Gy) a...

    journal_title：Investigational new drugs

    pub_type： 临床试验,杂志文章

    doi：10.1007/BF00873130

    authors： Rosell R,Carles J,Abad A,Jimeno JM,Moreno I,Barnadas A,Ribelles N,Haboubi N

    更新日期：1992-07-01 00:00:00

  • Effects of drug efflux proteins and topoisomerase I mutations on the camptothecin analogue gimatecan.

    abstract：:Clinically relevant resistance to the currently approved camptothecins, irinotecan and topotecan, is poorly understood but may involve increased expression of ATP-dependent drug transporters such as ABCG2 (breast cancer resistant protein, BCRP). Gimatecan (ST1481) is a lipophilic 7-substituted camptothecin derivative ...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-007-9093-0

    authors： Gounder MK,Nazar AS,Saleem A,Pungaliya P,Kulkarni D,Versace R,Rubin EH

    更新日期：2008-06-01 00:00:00

  • The activity of flavone acetic acid (NSC 347512) on human colon cancer cells in vitro.

    abstract：:Flavone acetic acid (FAA) was incubated for 1 to 48 hr with 3 established human colon cancer cell lines endowed with distinct degrees of phenotypic properties. All 3 lines responded to FAA in almost identical fashion; when incubated with the drug for only 1 hr, an initial decrease in survival was observed for concentr...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/BF00173501

    authors： Drewinko B,Yang LY

    更新日期：1986-01-01 00:00:00

  • Phase I study of mitonafide in 120 hour continuous infusion in non-small cell lung cancer.

    abstract：:Mitonafide is the lead compound of a new series of antitumor drugs, the 3-Nitronaphthalimides, which have shown antineoplastic activity in vitro as well as in vivo. This phase I Mitonafide study in non-small cell lung cancer using a 120-hour continuous infusion (120 h. C.I.) schedule of administration was designed to ...

    journal_title：Investigational new drugs

    pub_type： 临床试验,杂志文章

    doi：10.1007/BF00877242

    authors： Rosell R,Carles J,Abad A,Ribelles N,Barnadas A,Benavides A,Martin M

    更新日期：1992-08-01 00:00:00

  • Therapeutic efficacy and imaging assessment of the HER2-targeting chemotherapy drug ZHER2:V2-pemetrexed in lung adenocarcinoma Xenografts.

    abstract：:Chemotherapy has always been the first therapeutic option for patients with advanced non-small cell lung cancer (NSCLC) with untreatable oncogenic mutations. However, chemotherapy has demonstrated limited success and is associated with severe side effects. This research aimed to investigate the antitumor efficacy and ...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-019-00876-3

    authors： Han J,Zhao Y,Zhao X,Ma T,Hao T,Liu J,Zhang Z,Zhang J,Wang J

    更新日期：2020-08-01 00:00:00

  • Phase II trial of taxol in patients with adenocarcinoma of the upper gastrointestinal tract (UGIT). The Eastern Cooperative Oncology group (ECOG) results.

    abstract：:Taxol was administered as a 24-hour continuous infusion at 250 mg/m2 in this Phase II trial in patients with adenocarcinomas of the upper gastrointestinal tract (UGIT). Twenty-five patients were entered between July 1991 and June 1992, twenty-three were eligible and were evaluated for toxicity and twenty-two were asse...

    journal_title：Investigational new drugs

    pub_type： 临床试验,杂志文章

    doi：10.1007/BF00873804

    authors： Einzig AI,Lipsitz S,Wiernik PH,Benson AB 3rd

    更新日期：1995-01-01 00:00:00

  • Phase II trial of 5 day continuous intravenous infusion of 6-thioguanine in patients with recurrent and metastatic squamous cell carcinoma of the head and neck.

    abstract：:Fifteen patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck received a 5 day continuous I.V. infusion of 6-thioguanine repeated every five weeks. Dose limiting toxicity was primarily hematological with grade III/IV leucopenia and thrombocytopenia seen in seven patients. Nausea and vo...

    journal_title：Investigational new drugs

    pub_type： 临床试验,杂志文章

    doi：10.1007/BF00873122

    authors： Kruter F,Eisenberger M,Sinibaldi V,Engstrom C,Jacobs M,Abrams J,Belani C,Gray W,Krasnow S

    更新日期：1992-07-01 00:00:00

  • Synergistic combination of menogarol and melphalan and other two drug combinations.

    abstract：:Menogarol is a new anthracycline undergoing phase I clinical trial. We report here the lethality after 2 hr exposure to 2 drug combinations of menogarol and several antitumor agents. A new statistical procedure was used to identify synergistic combinations. Most of these combinations were additive, except for menogaro...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/BF00179427

    authors： Bhuyan BK,Adams EG,Johnson M,Crampton SL

    更新日期：1985-01-01 00:00:00

  • Prolonged infusion of gemcitabine in advanced solid tumors: a phase-I-study.

    abstract：BACKGROUND:Gemcitabine is a pro-drug that has to be phosphorylated to gemcitabine-triphosphate in order to exhibit its antineoplastic activity. This reaction involves the enzyme deoxycytidine kinase which is saturated at plasma concentrations following standard 30-min infusions. Pharmacological studies indicate that pr...

    journal_title：Investigational new drugs

    pub_type： 临床试验,杂志文章

    doi：10.1007/s10637-005-5859-4

    authors： Schmid P,Schweigert M,Beinert T,Flath B,Sezer O,Possinger K

    更新日期：2005-03-01 00:00:00

  • Clinical pharmacokinetic/pharmacodynamic and physiologically based pharmacokinetic modeling in new drug development: the capecitabine experience.

    abstract：:Preclinical studies, along with Phase I, II, and III clinical trials demonstrate the pharmacokinetics, pharmacodynamics, safety and efficacy of a new drug under well controlled circumstances in relatively homogeneous populations. However, these types of studies generally do not answer important questions about variabi...

    journal_title：Investigational new drugs

    pub_type： 杂志文章,评审

    doi：10.1023/a:1023525513696

    authors： Blesch KS,Gieschke R,Tsukamoto Y,Reigner BG,Burger HU,Steimer JL

    更新日期：2003-05-01 00:00:00

  • Antiproliferative activity, mechanism of action and oral antitumor activity of CP-4126, a fatty acid derivative of gemcitabine, in in vitro and in vivo tumor models.

    abstract：:Gemcitabine is a deoxycytidine (dCyd) analog with activity in leukemia and solid tumors, which requires phosphorylation by deoxycytidine kinase (dCK). Decreased membrane transport is a mechanism of resistance to gemcitabine. In order to facilitate gemcitabine uptake and prolong retention in the cell, a lipophilic pro-...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-009-9377-7

    authors： Bergman AM,Adema AD,Balzarini J,Bruheim S,Fichtner I,Noordhuis P,Fodstad O,Myhren F,Sandvold ML,Hendriks HR,Peters GJ

    更新日期：2011-06-01 00:00:00

  • Antiproliferative effects of ZD0473 (AMD473) in combination with 5-fluorouracil or SN38 in human colorectal cancer cell lines.

    abstract：PURPOSE:ZD0473 (AMD473) [cis-amminedichloro(2-methylpyridine) platinum(II)] is a novel platinum agent of proven activity in vitro against a variety of human tumor-derived cell lines even with intrinsic or acquired resistance to CDDP. The aim of this study is to provide the basis for a rational design of ZD0473-based co...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1023/B:DRUG.0000036682.99818.71

    authors： Plasencia C,Abad A,Martinez-Balibrea E,Taron M

    更新日期：2004-11-01 00:00:00

  • First-in-human phase I dose escalation study of MK-8033 in patients with advanced solid tumors.

    abstract：:Background C-Met, which is frequently activated in multiple cancers, has been implicated in tumor formation, progression, metastasis, angiogenesis, and resistance to multiple therapies. MK-8033 is a small-molecule inhibitor of c-Met that binds preferentially to the activated conformation, and has demonstrated anti-tum...

    journal_title：Investigational new drugs

    pub_type： 杂志文章,多中心研究

    doi：10.1007/s10637-018-0567-z

    authors： Keedy VL,Lenz HJ,Saltz L,Whisenant JG,Berlin JD,Camacho LH

    更新日期：2018-10-01 00:00:00