Contents
Academic literature on the topic 'A-007 prodrugs'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'A-007 prodrugs.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Journal articles on the topic "A-007 prodrugs"
1
Sagiraju, Sarada, and Branko S. Jursic. "NMR spectroscopic study of cyclodextrin inclusion complexes with A-007 prodrugs." Carbohydrate Research 343, no. 7 (May 2008): 1180–90. http://dx.doi.org/10.1016/j.carres.2008.03.014.
Full text
2
Bussel, James B., Allison M. Schindler, and Elliott B. Grossbard. "R935788: A Phase II, Single Center, Open Label, Efficacy and Safety, Ascending Dose, Pilot Study for the Treatment of Adult Immune Thrombocytopenic Purpura (ITP)." Blood 110, no. 11 (November 16, 2007): 1310. http://dx.doi.org/10.1182/blood.v110.11.1310.1310.
Full textAbstract:
Abstract Syk kinase is central to FcR and B-cell signaling in inflammatory cells. By inhibiting syk, and thereby IgG signaling, R788 (a small molecule prodrug for biologically active R406), inhibits the downstream activation of mast cells, macrophages and B-cells. (Braselmann S. Pharm Exp Ther. 2006). Preclinical study showed that R788 minimized thrombocytopenia in mice treated with anti-platelet antibodies (Crow, A.R. Blood 2005). In this study, adult, refractory ITP patients (pts) were treated with escalating doses of R788 in cohorts of ≥3 pts to evaluate safety and efficacy. After a cohort completed four weeks, the next cohort could be initiated. Pts completed 2 weeks of dosing before the dose could be increased (by 25 mg twice daily). Dosing was initiated at 75mg PO BID to 150 mg PO BID. Pts who responded and then had their platelet (plt) counts (cts) decline, could have their dose increased to a maximum of 175mg bid. Safety: 14 pts entered the study, 10 after failed splenectomy and 5 who were >70 yo. Six pts withdrew due to failure to respond (4) or gastrointestinal (GI) symptoms (2). GI symptoms (vomiting & diarrhea) were seen in 5 of 14 pts with mild elevations in ALT in 2 pts (2 >2XULN, one of whom had pre-existing hepatitis). Two pts were hospitalized for GI side effects (dehydration) and one developed an unrelated UTI with subsequent diagnosis of DVT. R788 also elevated blood pressure in some pts but appeared to not have a significant effect on neutrophil counts. Efficacy: By protocol standards, 9/14 pts are considered responders with stable platelet counts > 30,000/ul (30k). Six pts had peak counts > 100k. The mean change from pre treatment to the peak count in the 8 on study pts was 125k. Two pts, who previously had failed a wide range of other treatments, have maintained counts generally above 20k completing > 20 weeks of study with 0 and 1 IVIG treatments respectively, in each for the first time in > 10 years that they achieved prolonged avoidance of IVIG. Five had not responded to a thrombopoietic agent, 2 of whom responded to R788. Two responders discontinued the study because of nausea and vomiting at the dose that provided a response. Conclusions: The effects of R788 treatment are preliminary but, despite GI toxicity in certain patients, nonetheless impressive in this very refractory ITP population. Certain pts have had important clinical although numerically unimpressive benefit. Further studies are ongoing including studies of FcR expression before and after treatment. Patients Currently On Study Patient Baseline Plt Count x 109/L Peak Plt Count x 109/L (w/o IVIG) Most Recent Plt Count x 109/L Total Wks On Study Current Dose 001 14 49 20 30 175mg BID 002 22 222 18 24 175mg BID 003 32 158 37 24 150mg BID 007 20 111 40 21 100mg BID 008 22 205 205 19 125mg BID 009 46 329 329 14 100mg BID 011 45 124 124 11 125mg BID 014 107 107 36 6 125mg BID Mean 38 163 Patients Withdrawn From Study Patients Baseline Plt Count x 109/L Peak Plt Count x 109/L (w/o IVIG) End Of Study Plt Count x 109/L Total Wks On Study Highest Dose 004 12 11 11 19 175mg BID 005 12 66 11 14 150mg BID 010 18 13 21 11 175mg BID 012 17 17 14 3 125mg BID 013 25 159 97 5 150mg BID 015 3 13 13 4 125mg BID Mean 14 46
3
Denora, Nunzio, Valentino Laquintana, Angela Lopedota, Mariangela Serra, Laura Dazzi, Giovanni Biggio, Dhananjay Pal, et al. "Novel L-Dopa and Dopamine Prodrugs Containing a 2-Phenyl-imidazopyridine Moiety." Pharmaceutical Research 24, no. 7 (April 3, 2007): 1309–24. http://dx.doi.org/10.1007/s11095-007-9255-y.
Full text
4
Niemans, R., A. Yaromina, J. Theys, A. Ashoorzadeh, R. Anderson, M. Bull, C. Guise, et al. "OC-0236: DTP-006: a novel, orally bioavailable hypoxia-activated prodrug." Radiotherapy and Oncology 119 (April 2016): S107. http://dx.doi.org/10.1016/s0167-8140(16)31485-2.
Full text
5
Seay, Kieran, Nazanin Khajoueinejad, Jian Hua Zheng, Patrick Kiser, Christina Ochsenbauer, John C. Kappes, Betsy Herold, and Harris Goldstein. "The Vaginal Acquisition and Dissemination of HIV-1 Infection in a Novel Transgenic Mouse Model Is Facilitated by Coinfection with Herpes Simplex Virus 2 and Is Inhibited by Microbicide Treatment." Journal of Virology 89, no. 18 (July 8, 2015): 9559–70. http://dx.doi.org/10.1128/jvi.01326-15.
Full textAbstract:
ABSTRACTEpidemiological studies have demonstrated that herpes simplex virus 2 (HSV-2) infection significantly increases the risk of HIV-1 acquisition, thereby contributing to the expanding HIV-1 epidemic. To investigate whether HSV-2 infection directly facilitates mucosal HIV-1 acquisition, we used our transgenic hCD4/R5/cT1 mouse model which circumvents major entry and transcription blocks preventing murine HIV-1 infection by targeting transgenic expression of human CD4, CCR5, and cyclin T1 genes to CD4+T cells and myeloid-committed cells. Productive infection of mucosal leukocytes, predominantly CD4+T cells, was detected in all hCD4/R5/cT1 mice intravaginally challenged with an HIV-1 infectious molecular clone, HIV-Du151.2env-NLuc, which expresses anenvgene (C.Du151.2) cloned from an acute heterosexually infected woman and a NanoLuc luciferase reporter gene. Lower genital tract HIV-1 infection after HIV-Du151.2env-NLuc intravaginal challenge was increased ∼4-fold in hCD4/R5/cT1 mice coinfected with HSV-2. Furthermore, HIV-1 dissemination to draining lymph nodes was detected only in HSV-2-coinfected mice. HSV-2 infection stimulated local infiltration and activation of CD4+T cells and dendritic cells, likely contributing to the enhanced HIV-1 infection and dissemination in HSV-2-coinfected mice. We then used this model to demonstrate that a novel gel containing tenofovir disoproxil fumarate (TDF), the more potent prodrug of tenofovir (TFV), but not the TFV microbicide gel utilized in the recent CAPRISA 004, VOICE (Vaginal and Oral Interventions to Control the Epidemic), and FACTS 001 clinical trials, was effective as preexposure prophylaxis (PrEP) to completely prevent vaginal HIV-1 infection in almost half of HSV-2-coinfected mice. These results also support utilization of hCD4/R5/cT1 mice as a highly reproducible immunocompetent preclinical model to evaluate HIV-1 acquisition across the female genital tract.IMPORTANCEMultiple epidemiological studies have reported that genital herpes simplex virus 2 (HSV-2) infection increases the risk of HIV-1 sexual acquisition by severalfold. Understanding the underlying mechanisms by which HSV-2 facilitates HIV-1 infection and optimizing the efficacy of therapies to inhibit HIV-1 infection during HSV-2 coinfection should contribute to reducing HIV-1 transmission. Using our novel transgenic hCD4/R5/cT1 mouse model infectible with HIV-1, we demonstrated that HSV-2 infection enhances vaginal transmission and dissemination of HIV-1 infection while stimulating recruitment and activation of CD4+T cells and dendritic cells in the lower genital tract. HIV acquisition by hCD4/R5/cT1 mice vaginally coinfected with HSV-2 could be completely prevented in almost half the mice by preexposure prophylaxis (PrEP) with a novel gel containing tenofovir disoproxil fumarate (TDF), the tenofovir prodrug, but not with the tenofovir microbicide gel utilized in CAPRISA-004, VOICE, and FACTS-001 clinical trials. The hCD4/R5/cT1 mice represent a new preclinical mouse model to evaluate vaginal HIV-1 acquisition.
6
Joerger, Markus, Anastasios Stathis, Ioannis Metaxas, Dagmar Hess, Aurelius Gabriel Omlin, Gisela Mayer, Sheila Gaggetta, et al. "A phase I study to assess the safety, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activities of BAL101553, a novel tumor checkpoint controller (TCC), administered as 48-hour infusion in adult patients with advanced solid tumors." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): TPS2602. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.tps2602.
Full textAbstract:
TPS2602 Background: BAL101553 (prodrug of BAL27862), is a novel TCC that promotes tumor cell death by modulating the spindle assembly checkpoint. BAL27862 has shown potent antitumor activity in diverse preclinical tumor models, including models refractory to standard therapies. In a completed Phase 1 study using 2-h IV infusions (Days 1, 8, 15, q28d, NCT01397929 , CDI-CS-001, Lopez et al. JCO 34, 2016 suppl; 2525) dose-limiting vascular effects were observed and appeared Cmax related. The recommended Phase 2 dose for 2-h IV BAL101553 is 30 mg/m2. Vascular toxicity was not observed in an ongoing study with oral BAL101553 (NCT02490800, CDI-CS-002) at daily doses up to 30 mg (QD). Preclinical data suggest that antiproliferative effects of BAL101553/27862 are driven by exposure (AUC); thus vascular toxicity and antitumor activity are mediated by different PK drivers. BAL27862 has a half-life of ~15 h. Based on PK-modeling, extending the infusion from 2 h to 48 h was expected to result in ~4-fold higher AUC at a given Cmaxlevel and thereby improve the therapeutic window. Methods: This is an ongoing multicenter, open-label, Phase 1 dose-escalation study (NCT02895360, CDI-CS-003/SAKK67/15) using a 3+3 design to determine the MTD, characterize dose-limiting toxicities and assess the PK, PD and antitumor activities of 48-h infusions of BAL101553 in consecutive 28-day cycles at a starting dose of 30 mg/m2 administered on Day 1, 8 and 15 (q28d). The dose escalation scheme foresees up to ~ 50% dose increments depending on observed toxicities. During cycle 2, patients receive 7 days oral (QD) BAL101553 (Day 15–21) instead of the weekly IV infusion to assess absolute oral bioavailability. Patients with histologically-confirmed advanced or recurrent solid tumors are eligible for enrollment. Adverse events are assessed using CTCAEv4; tumor response by RECIST 1.1 (every 2 cycles). PD assessments include optional tumor biopsies and circulating tumor cells. PK profiles are assessed during the first 2 cycles. Two dose cohorts (30 and 45 mg/m2) have completed without DLTs or signs of vascular toxicity. Clinical trial information: NCT02895360.
7
Reid, Tony R., Jeffrey R. Infante, Howard A. Burris, Curtis Scribner, Susan Jane Knox, Bryan Oronsky, Janet L. Stephens, and Jan Scicinski. "Activity observed in a phase I dose escalation trial of the hypoxia-activated, NO prodrug, RRx001." Journal of Clinical Oncology 31, no. 4_suppl (February 1, 2013): 241. http://dx.doi.org/10.1200/jco.2013.31.4_suppl.241.
Full textAbstract:
241 Background: RRx-001, the first member of a new class of anticancer compounds sourced from the defense industry, is a hypoxia-selective, nitrite reductase-activated prodrug of nitric oxide (NO). The active metabolites selectively enhance oxidative and nitrosative stress in cancer cells through glutathione depletion, ROS formation, and the generation of high local concentrations of NO. The objectives of this Phase 1 dose-escalation trial were to investigate safety, dose-limiting toxicities (DLTs), pharmacodynamics and pharmacokinetics (PK) of RRx-001. Methods: Eligible patients had advanced solid tumor malignancies; ECOG PS 0-2; adequate bone marrow function. In a 3+3 escalation design, RRx-001 was administered intravenously (IV) over 2-3 hours once weekly for 8 weeks to patients with advanced cancer in successive dose-escalating cohorts. PK was collected on days 1 and 50, and tumor blood flow, assessed by CEUS or DCE/DWI-MRI, was performed on days 1 and 8. Tumor response was determined every 8 weeks. Results: To date 12 patients have been dosed across 3 successive cohorts (10, 16.7, and 24.6 mg/m2). Tumor types included pancreas (3), colorectal (5), head and neck (2), melanoma (1), and cholangiocarcinoma (1). No DLTs or treatment-associated SAEs were observed. Transient infusion site pain was reported in 10/12 patients, grade 1 (9/10) or grade 2 (1/10), generally managed by lengthening the infusion duration and using peripheral venous access. No relevant treatment-related changes in laboratory values were observed. Seven patients were evaluable for response, with 1 partial response (parotid tumor). Three patients had stable disease ≥ 2 months (2 pancreas, 1 colorectal with treatment duration 10+ months, exceeding the response to his previous chemo regimen). One pancreas patient with an increase in tumor size due to treatment-related central necrosis was diagnosed with pseudoprogression and remained on study for 4 months. Conclusions: RRx-001, an anticancer agent with a novel structure and mechanism of action, is well tolerated with mild infusion-site pain. PK and PD data will be presented. Escalation is ongoing, but preliminary evidence of anti-tumor activity is promising. Clinical trial information: NCT01359982.
8
Marcial-Coba, Martín S. "Scientifically unproven treatments for COVID-19." Bionatura 5, no. 4 (November 15, 2020): 1295–96. http://dx.doi.org/10.21931/rb/2020.05.04.3.
Full textAbstract:
Detected for the first time in late December 2019, a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the causative agent of an international outbreak of coronavirus disease 2019 (COVID-19). In late August 2020, approx. 24 000 000 cases, including 815 038 deaths, have been confirmed worldwide1. The WHO declared the outbreak of COVID-19 as a Public Health Emergency of International Concern, and it has been proposed that its spread may be interrupted by early detection, isolation, the implementation of a robust system to trace contacts, and a prompt treatment2. Nevertheless, there has not yet been any vaccine or effective treatment that has received approval3. Despite this, the FDA has recently issued an emergency use authorization for the investigational antiviral drug Remdesivir to treat COVID-19 in patients with severe disease4. Although there is still limited information regarding the safety and efficacy of this novel prodrug, it has shown potent in vitro antiviral activity against SARS-CoV-2 isolates, and therapeutic efficacy in animal models5.
9
Garraza, María Soledad, María Emilia Gimenez, Daniel Roberto Vega, and Ricardo Baggio. "Crystal structure and pseudosymmetry analysis of the triclinic prodrug cloxazolam (Z′ = 4)." Acta Crystallographica Section C Structural Chemistry 75, no. 7 (June 26, 2019): 851–58. http://dx.doi.org/10.1107/s2053229619008404.
Full textAbstract:
The prodrug cloxazolam [systematic name: 13-chloro-2-(2-chlorophenyl)-3-oxa-6,9-diazatricyclo[8.4.0.02,6]tetradeca-1(10),11,13-trien-8-one], C17H14Cl2N2O2, crystallizes in the triclinic space group P\overline{1}, with four chemically identical independent molecules in the asymmetric unit. However, in order to facilitate the analysis of the striking pseudosymmetry relating the four independent molecules, the structure has been analysed and reported in the nonconventional centred B\overline{1} space-group setting. Pseudosymmetry is an eminently local property, valid only in the realm of the unit-cell boundary and not propagating to the whole crystal structure. It has been analyzed using the MP procedure described in the preceding article [Baggio (2019). Acta Cryst. C75, 837–850]. The molecules consist of a rigid core made up of three rings (five-, six- and seven-membered) and an extra six-membered ring joined to the latter group by a single C—C bond, together with a clamping intramolecular C—H...O interaction preventing free rotation and providing additional rigidity. The four molecules in the asymmetric unit pair into dimers with almost exact twofold pseudosymmetry, further linked into (001) slabs as the building bricks of the structure. Interpenetration of slabs finally leads to a three-dimensional structure of unusual compactness for an organic structure, with a Kitaigorodskii packing index of ca 0.71.
10
Kehrer, Diederik F. S., Ron H. J. Mathijssen, Jaap Verweij, Peter de Bruijn, and Alex Sparreboom. "Modulation of Irinotecan Metabolism by Ketoconazole." Journal of Clinical Oncology 20, no. 14 (July 15, 2002): 3122–29. http://dx.doi.org/10.1200/jco.2002.08.177.
Full textAbstract:
PURPOSE: Irinotecan (CPT-11) is a prodrug of SN-38 and has been registered for the treatment of advanced colorectal cancer. It is converted by the cytochrome P450 3A4 isozyme (CYP3A4) into several inactive metabolites, including 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin (APC). To investigate the role of CYP3A4 in irinotecan pharmacology, we evaluated the consequences of simultaneous treatment of irinotecan with a potent enzyme inhibitor, ketoconazole, in a group of cancer patients. PATIENTS AND METHODS: A total of seven assessable patients was treated in a randomized, cross-over design with irinotecan (350 mg/m2 intravenously for 90 minutes) given alone and followed 3 weeks later by irinotecan (100 mg/m2) in combination with ketoconazole (200 mg orally for 2 days) or vice versa. Serial plasma, urine, and feces samples were obtained up to 500 hours after dosing and analyzed for irinotecan, metabolites (7-ethyl-10-hydroxycamptothecin [SN-38], SN-38 glucuronide [SN-38G], and APC), and ketoconazole by high-performance liquid chromatography. RESULTS: With ketoconazole coadministration, the relative formation of APC was reduced by 87% (P = .002), whereas the relative exposure to the carboxylesterase-mediated SN-38 as expected on the basis of dose (area under the plasma concentration-time curve normalized to dose) was increased by 109% (P = .004). These metabolic alterations occurred without substantial changes in irinotecan clearance (P = .90) and formation of SN-38G (P = .93). CONCLUSION: Inhibition of CYP3A4 in cancer patients treated with irinotecan leads to significantly increased formation of SN-38. Simultaneous administration of various commonly prescribed inhibitors of CYP3A4 can potentially result in fatal outcomes, and up to four-fold reductions in irinotecan dose are indicated.
Dissertations / Theses on the topic "A-007 prodrugs"
1
Sagiraju, Sarada. "Synthesis and Spectroscopic Study of Anticancer agent A-007 Prodrugs and Progress Towards the Synthesis of Tetramic acid Antibiotics." ScholarWorks@UNO, 2008. http://scholarworks.uno.edu/td/900.
Full textAbstract:
4, 4'-Dihydroxybenzophenone-2, 4-dinitrophenylhydrazone (A-007) has recently completed a phase-I clinical trial, and objective responses were seen in advanced breast cancer, lung cancer, ovarian cancer, melanoma, skin cancer and non-Hodgkin's lymphoma. Despite the promising results in the clinical trials, the major disadvantage to using A-007 as a broad-scale therapeutic is its poor water solubility. To make use of this promising anticancer drug either orally or intravenously, the short-term obstacle must be to overcome the limited solubility of A-007 in water. There are several approaches to overcome this obstacle. The first approach is to make hydrolysable prodrugs of A-007. The second approach is to make an A-007 complex with a water soluble host, such as cyclodextrin. We used a combination of these two previously described methods, i.e. transforming A-007 into a more water soluble prodrugs and then further increasing the prodrug water solubility by making their cyclodextrin inclusion complexes. Our syntheses and spectroscopic explorations of A-007 prodrugs are presented in this dissertation. Tetramic acid (2, 4 pyrrolidine-2, 4-dione ring system) containing compounds have been found to display a remarkable diversity of biological activities and have attracted the interest of medicinal and synthetic chemists. Magnesidin (1-acetyl-3-octanoyl-5-ethylidene tetramic acid) has strong antimicrobial activity against bacteria that cause gingivitis and dental plaque. Current efforts toward the synthesis of Magnesidin are discussed along with the plans for the completion of synthesis.