A phase I pharmacokinetic study of the P-glycoprotein inhibitor, ONT-093, in combination with paclitaxel in patients with advanced cancer.

abstract：:We explored whether barasertib (AZD1152), a selective Aurora B kinase inhibitor, is a substrate for P-glycoprotein (Pgp, MDR1), breast cancer resistance protein (BCRP), and multidrug resistance protein 2 (MRP2) in vitro. Cell survival, drug transport, and competition experiments with barasertib pro-drug and the more a...

journal_title：Investigational new drugs

authors： Marchetti S,Pluim D,van Eijndhoven M,van Tellingen O,Mazzanti R,Beijnen JH,Schellens JH

更新日期：2013-10-01 00:00:00

abstract：:A series of 96 diarylamidine (and diarylimidazoline) derivatives were evaluated for their inhibitory effects on the growth and DNA synthesis of murine leukemia L1210 cells. The amidino- and imidazolino-substituted aryl moieties of the compounds consisted of phenyl, indole, indene, benzofuran, benzo[b]thiophene or benz...

journal_title：Investigational new drugs

authors： Balzarini J,de Clercq E,Dann O

更新日期：1983-01-01 00:00:00

abstract：:Over forty papers describing correlations between in vitro human tumor sensitivity to a variety of chemotherapeutic agents and the in vivo response of patients to those agents have been published since the publication in 1978 by Salmon and Hamburger of their results of a human tumor colony-forming chemosensitivity ass...

journal_title：Investigational new drugs

authors： Bradley EC,Issell BF,Hellman R

更新日期：1984-01-01 00:00:00

abstract：:We have recently developed a liposomal nanoparticle (LNP) formulation of irinotecan based on loading method that involves formation of a complex between copper and the water soluble camptothecin. The loading methodology developed for irinotecan was evaluated to develop a LNP topotecan formulation (referred to herein a...

journal_title：Investigational new drugs

authors： Patankar NA,Waterhouse D,Strutt D,Anantha M,Bally MB

更新日期：2013-02-01 00:00:00

abstract：:Fourteen patients with active chronic lymphocytic leukemia who had failed prior therapy were treated with progressive doses of weekly intravenous colchicine beginning at 2 mg and escalating as high as 7 mg in a single injection. Responses were seen in two of 14, with a lessening of adenopathy and splenomegaly. Toxicit...

journal_title：Investigational new drugs

authors： Weick JK,Livingston RB,Van Slyck EJ

更新日期：1983-01-01 00:00:00

abstract：:Compared to doxorubicin, equimolar epirubicin toxicity is reduced by about 50% by the epimerization of a hydrogen and hydroxyl group at the 4' position of the anthracycline sugar moiety. The circadian timing of doxorubicin administration markedly affects its lethal and sub-lethal bone marrow and gut toxicities in mice...

journal_title：Investigational new drugs

authors： Mormont MC,von Roemeling R,Sothern RB,Berestka JS,Langevin TR,Wick M,Hrushesky WJ

更新日期：1988-12-01 00:00:00

abstract：:Background AR-67 is a novel camptothecin analogue at early stages of drug development. The phase 1 clinical trial in cancer patients with solid tumors was completed and a population pharmacokinetic model (POP PK) was developed to facilitate further development of this investigational agent. Methods Pharmacokinetic dat...

journal_title：Investigational new drugs

authors： Tang F,Tsakalozou E,Arnold SM,Ng CM,Leggas M

更新日期：2019-12-01 00:00:00

abstract：:LP-261 is a novel tubulin targeting anticancer agent that binds at the colchicine site on tubulin, inducing G2/M arrest. Screening in the NCI60 cancer cell lines resulted in a mean GI50 of approximately 100 nM. Here, we report the results of testing in multiple mouse xenograft models and angiogenesis assays, along wit...

journal_title：Investigational new drugs

authors： Gardner ER,Kelly M,Springman E,Lee KJ,Li H,Moore W,Figg WD

更新日期：2012-02-01 00:00:00

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

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

更新日期：2005-03-01 00:00:00

abstract：:The aim of this study was to determine the antitumor activity of irofulven when administered in combination with a variety of antimitotic agents. Irofulven in combination with either paclitaxel or docetaxel demonstrated synergistic activity in both the in vitro and in vivo studies. The majority of xenograft bearing an...

journal_title：Investigational new drugs

authors： Kelner MJ,McMorris TC,Rojas RJ,Trani NA,Velasco TR,Estes LA,Suthipinijtham P

更新日期：2002-08-01 00:00:00

abstract：:Bcl-2 family proteins are the key regulators of the intrinsic apoptotic pathway, controlling the point-of no-return and setting the threshold to engage the death machinery in response to chemical damage. Bcl-2 proteins have emerged as attractive targets for anti-cancer drug development. Navitoclax is a selective, pote...

journal_title：Investigational new drugs

authors： Vlahovic G,Karantza V,Wang D,Cosgrove D,Rudersdorf N,Yang J,Xiong H,Busman T,Mabry M

更新日期：2014-10-01 00:00:00

abstract：:Glioblastoma is a fast-growing primary brain tumor observed in adults with the worst prognosis. Preclinical studies have demonstrated the encouraging anticancer activity of statins. This study evaluated the efficacy of atorvastatin in combination with standard therapy in patients with glioblastoma. In this prospective...

journal_title：Investigational new drugs

authors： Altwairgi AK,Alghareeb WA,AlNajjar FH,Alhussain H,Alsaeed E,Balbaid AAO,Aldanan S,Orz Y,Alsharm AA

更新日期：2020-08-27 00:00:00

abstract：:The matrix metalloproteinases (MMPs) are a family of at least fifteen secreted and membrane-bound zinc-endopeptidases. Collectively, these enzymes can degrade all of the components of the extracellular matrix, including fibrallar and non-fibrallar collagens, fibronectin, laminin and basement membrane glycoproteins. MM...

journal_title：Investigational new drugs

authors： Wojtowicz-Praga SM,Dickson RB,Hawkins MJ

更新日期：1997-01-01 00:00:00

abstract：INTRODUCTION:Heat shock protein 90 (Hsp90) has been studied as a therapeutic target in many cancers. In preclinical trials, the Hsp90 ATPase inhibitor ganetespib demonstrated potent inhibition of solid tumor growth, with superior potency than prior Hsp90 inhibitors. Given the promising preclinical outcome and favorable...

journal_title：Investigational new drugs

authors： Thakur MK,Heilbrun LK,Sheng S,Stein M,Liu G,Antonarakis ES,Vaishampayan U,Dzinic SH,Li X,Freeman S,Smith D,Heath EI

更新日期：2016-02-01 00:00:00

abstract：:Background To determine the recommended dose (RD) of a combination of PM01183 and gemcitabine in patients with advanced solid tumors. Methods Forty-five patients received escalating doses of PM01183/gemcitabine on Days 1 and 8 every 3 weeks (d1,8 q3wk) following a standard 3 + 3 design. Results PM01183 3.5 mg flat dos...

journal_title：Investigational new drugs

authors： Paz-Ares L,Forster M,Boni V,Szyldergemajn S,Corral J,Turnbull S,Cubillo A,Teruel CF,Calderero IL,Siguero M,Bohan P,Calvo E

更新日期：2017-04-01 00:00:00

abstract：PURPOSE:Hepatobiliary cancers respond poorly to cytotoxic chemotherapy. We evaluated the activity and safety of ixabepilone, an epothilone B analogue which stabilizes microtubules, in a phase II trial in patients with advanced cancers of the gallbladder, bile duct, and liver. METHODS:Eligible patients had previously-u...

journal_title：Investigational new drugs

authors： Nimeiri HS,Singh DA,Kasza K,Taber DA,Ansari RH,Vokes EE,Kindler HL

更新日期：2010-12-01 00:00:00

abstract：:Introduction In preclinical data, the combination therapy with S-1 and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) had a synergistic antitumor effect on non-small cell lung cancer (NSCLC), regardless of the EGFR mutation status. Patients and Methods Patients with previously treated NSCLC an...

journal_title：Investigational new drugs

authors： Nakahara Y,Shimokawa T,Misumi Y,Nogami N,Shinkai T,Seki N,Hosomi Y,Hida N,Okamoto H

更新日期：2020-08-15 00:00:00

abstract：:Studies with CGP 41 251 (I), an N-benzoylstaurosporine derivative and PKC-alpha inhibitor, revealed that oral administration of 400 microg/day of the compound to wild type mice on four successive days reversed multi drug resistance (Killion et al. Oncology Research 7: 453-459, 1995). In our study, the same regimen of ...

journal_title：Investigational new drugs

authors： van Gijn R,van Tellingen O,Haverkate E,Kettenes-van den Bosch JJ,Bult A,Beijnen JH

更新日期：1999-01-01 00:00:00

abstract：BACKGROUND:Relatively few studies have examined the activity of alkylating agents in the treatment of advanced colorectal adenocarcinoma. Recent reports have suggested possible therapeutic activity for high-dose intravenous melphalan administered with autologous bone marrow transplantation (BMT) support. We conducted a...

journal_title：Investigational new drugs

authors： Moore DF Jr,Pazdur R,Abbruzzese JL

更新日期：1994-01-01 00:00:00

abstract：:An inflammatory myofibroblastic tumor (IMT) is a rare invasive soft tissue mass with intramuscular penetration that is primarily treated via a surgical procedure. However, with unclear boundaries and a high rate of relapse, there is no standard treatment for recurrence or unresectable tumors. It is noteworthy that app...

journal_title：Investigational new drugs

authors： Liu W,Duan Q,Gong L,Yang Y,Huang Z,Guo H,Niu X

更新日期：2020-09-11 00:00:00

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

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

abstract：:Background This first-in-human phase 1 study assessed the safety of TAS-114, a novel deoxyuridine triphosphatase inhibitor, combined with S-1 to determine its maximum tolerated dose (MTD) and recommended dose (RD). Methods In this dose-escalation study with a 3 + 3 design, TAS-114 and S-1 were concurrently administere...

journal_title：Investigational new drugs

authors： Doi T,Yoh K,Shitara K,Takahashi H,Ueno M,Kobayashi S,Morimoto M,Okusaka T,Ueno H,Morizane C,Okano N,Nagashima F,Furuse J

更新日期：2019-06-01 00:00:00

abstract：:Receptor tyrosine kinases (RTKs) modulate a variety of cellular events, including cell proliferation, differentiation, mobility and apoptosis. In addition, RTKs have been validated as targets for cancer therapies. Microtubules are another class of proven targets for many clinical anticancer drugs. Here, we report that...

journal_title：Investigational new drugs

authors： Zhang J,Zhou J,Ren X,Diao Y,Li H,Jiang H,Ding K,Pei D

更新日期：2012-04-01 00:00:00

abstract：:Aims A primary objective of this study was to investigate the effect of single and multiple doses of alisertib, an investigational Aurora A kinase inhibitor, on the QTc interval in patients with advanced malignancies. The dose regimen used was the maximum tolerated dose which was also the recommended phase 3 dose (50 ...

journal_title：Investigational new drugs

authors： Zhou X,Nemunaitis J,Pant S,Bauer TM,Patel M,Sarantopoulos J,Craig Lockhart A,Goodman D,Huebner D,Mould DR,Venkatakrishnan K

更新日期：2018-04-01 00:00:00

abstract：:Purpose Preclinical evidence suggests dichloroacetate (DCA) can reverse the Warburg effect and inhibit growth in cancer models. This phase 1 study was undertaken to assess the safety, recommended phase 2 dose (RP2D), and pharmacokinetic (PK) profile of oral DCA in patients with advanced solid tumors. Patients and Meth...

journal_title：Investigational new drugs

authors： Chu QS,Sangha R,Spratlin J,Vos LJ,Mackey JR,McEwan AJ,Venner P,Michelakis ED

更新日期：2015-06-01 00:00:00

abstract：:Cribrostatin 6 is a quinone-containing natural product that induces the death of cancer cell lines in culture, and its mechanism of action and scope of activity are unknown. Here we show that cribrostatin 6 has broad anticancer activity, potently inducing apoptotic cell death that is not preceded by any defined cell c...

journal_title：Investigational new drugs

authors： Hoyt MT,Palchaudhuri R,Hergenrother PJ

更新日期：2011-08-01 00:00:00

abstract：:Artemisinin and its derivatives are well known antimalarial drugs, particularly useful after resistance to traditional antimalarial pharmaceuticals has started to occur in Plasmodium falciparum. In recent years, anticancer activity of artemisinin has been reported both in vitro and in vivo. Artemisinin has inhibitory ...

journal_title：Investigational new drugs

authors： Buommino E,Baroni A,Canozo N,Petrazzuolo M,Nicoletti R,Vozza A,Tufano MA

更新日期：2009-10-01 00:00:00

abstract：:3-Deazaguanine (Dezaguanine), a purine antimetabolite, was evaluated in a phase I trial in 42 patients with advanced solid tumors. Dezaguanine was given as a weekly intravenous infusion for three consecutive weeks of a four-week cycle. The dose ranged from 30 to 2000 mg/m2; no consistent dose-limiting hematologic or g...

journal_title：Investigational new drugs

authors： Margolin K,Doroshow J,Leong L,Akman S,Carr B,Odujinrin O,Flanagan B,Grove W,DeLap R,Goldberg D

更新日期：1990-11-01 00:00:00

abstract：:Fifteen patients with advanced carcinoma of the breast who had failed prior chemotherapy, were treated with recombinant gamma interferon at a dose of 2mg/m2 (1mg = 2.4 X 10(7) international units) intravenously for five consecutive days every other week. The median patient age was 51 and all patients had a performance...

journal_title：Investigational new drugs

authors： Muss HB,Caponera M,Zekan PJ,Jackson DV Jr,Stuart JJ,Richards F,Cooper MR,Levin EA,Reich SD,Capizzi RL

更新日期：1986-01-01 00:00:00

abstract：:Drug lag, which delays patients' access to medicinal products, is typically associated with pharmaceutical regulations. To shorten drug lag, health authorities may establish new policies to liberalize the regulations, a step that is important in countries, such as Taiwan, with consumer demand for imported novel therap...

journal_title：Investigational new drugs

authors： Sun IC

更新日期：2019-10-01 00:00:00