Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Efavirenz is the lead compound of a series of benzoxazinones originally developed by DuPont Merck. It is a non-nucleoside reverse transcriptase inhibitor (NNRTI) under development for the potential treatment of viral infections, including HIV. In June 1998, the company submitted an NDA to the US FDA for the use of efavirenz (as Sustiva) for the treatment of HIV infection [289361]. In July 1998, DuPont purchased Merck's interest in DuPont Merck and the company's name changed to DuPont Pharmaceuticals. The two companies decided to continue to share marketing rights to Sustiva (to be marketed by Merck as Stocrin outside the US, Canada, and certain European countries) [291738]. As of October 1997, triple combination studies of efavirenz were ongoing, or planned, with nelfinavir, indinavir or ritonavir, or other retroviral inhibitors, for the treatment of opportunistic and pediatric viral infections [265945]. Efavirenz is also being evaluated as monotherapy and in combination with zidovudine (Retrovir, AZT) and lamivudine (Epivir, 3TC) (qv). Results of a study in eight HIV-infected patients, reported at the 12th World AIDS Conference in July 1998, showed that efavirenz administration, in dual and triple combinations, achieved HIV-RNA levels in plasma and cerebrospinal fluid (CSF) below the level of detection (fewer than 400 copies/ml) [290881,293994]. In March 1998, Merck signed a letter of intent with Trimeris to conduct a trial of efavirenz in combination with Trimeris's HIV fusion inhibitor, T-20, (qv). The trial will enroll up to 48 HIV-infected individuals at three sites in the US. All enrolled patients will be those who have begun to fail their existing triple combination therapy. Prior exposure to NNRTIs and protease inhibitors, other than indinavir, will be among the exclusion criteria for the study. The first 10 days of the study were planned as a dose-optimization period to assess the safety, pharmacokinetics and antiviral activity of multiple ascending doses of T-20. After completion of this period, subjects will be eligible to participate in an extension period of at least six months, during which T-20 will be administered in combination with efavirenz and two protease inhibitors [281696]. A 137-patient phase III study showed that efavirenz, in combination with zidovudine and lamivudine, caused significant reduction in viral levels and increased CD4 cell levels. The results were presented at the Sixth European Conference on Clinical Aspects and Treatment of HIV Infection (Hamburg, Germany, October 1997) [265945]. At the Fourth Conference on Retroviruses and Opportunistic Infections, in January 1997, data were presented from a clinical trial of efavirenz in combination with indinavir, which showed that, in 82% of the patients, viral load was reduced to undetectable levels, as measured by the Amplicor assay [231410]. Further retrospective analysis showed that the viral load was a significant predictor of long-term (over 52 weeks) viral suppression [265945]. A double-blind, phase II pilot study of efavirenz showed significant activity in HIV-RNA suppression and CD4 cell recovery when evaluated for two weeks alone, and even better results when used in combination with indinavir (Crixivan, qv); 80% of patients achieved HIV-RNA below level of quantification and CD4 cell count elevation averaging 140 cells/mm3. The study evaluated 16 patients for 12 weeks and is ongoing [219671,227966]. A total of 21 patients received indinavir (800 mg, eight hourly) for two weeks, followed by combination therapy with efavirenz (200 mg, once daily). Another group of nine patients received indinavir alone for 26 weeks, followed by the addition of stavudine (Zerit) and efavirenz. In combination use, indinavir dosing was 1.0 g every eight hours. At 26 weeks, approximately 40% of the patients receiving indinavir alonehad plasma levels below 400 copies/ml of HIV-RNA. After stavudine and efavirenz were added, and following 16 weeks of the triple combination, 83% of the patients had plasma levels below 400 copies/ml [247754].
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PMID:Efavirenz DuPont Pharmaceuticals Co. 1846 25

To investigate the dynamics of circRNA expression in pig testes, we designed specific strategies to individually study circRNA production from intron lariats and circRNAs originating from back-splicing of two exons. By applying these methods on seven Total-RNA-seq datasets sampled during the testicular puberty, we detected 126 introns in 114 genes able to produce circRNAs and 5,236 exonic circRNAs produced by 2,516 genes. Comparing our RNA-seq datasets to datasets from the literature (embryonic cortex and postnatal muscle stages) revealed highly abundant intronic and exonic circRNAs in one sample each in pubertal testis and embryonic cortex, respectively. This abundance was due to higher production of circRNA by the same genes in comparison to other testis samples, rather than to the recruitment of new genes. No global relationship between circRNA and mRNA production was found. We propose ExoCirc-9244 (SMARCA5) as a marker of a particular stage in testis, which is characterized by a very low plasma estradiol level and a high abundance of circRNA in testis. We hypothesize that the abundance of testicular circRNA is associated with an abrupt switch of the cellular process to overcome a particular challenge that may have arisen in the early stages of steroid production. We also hypothesize that, in certain circumstances, isoforms and circular transcripts from different genes share functions and that a global regulation of circRNA production is established. Our data indicate that this massive production of circRNAs is much more related to the structure of the genes generating circRNAs than to their function. Abbreviations: PE: Paired Ends; CR: chimeric Read; SR: Split Read; circRNA: circular RNA; NC: non conventional; ExoCirc-RNA: exonic circular RNA; IntroLCirc-: name of a porcine intronic lariat circRNA; ExoCirc-: name of a porcine exonic circRNA; IntronCircle-: name of a porcine intron circle; sisRNA: stable intronic sequence RNA; P: porcine breed Pietrain; LW: porcine breed Large White; RT: reverse transcription/reverse transcriptase; Total-RNA-seq: RNA-seq obtained from total RNA after ribosomal depletion; mRNA-seq: RNA-seq of poly(A) transcripts; TPM: transcripts per million; CR-PM: chimeric reads per million; RBP: RNA binding protein; miRNA: micro RNA; E2: estradiol; DHT: dihydrotestesterone.
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PMID:Analysis of pig transcriptomes suggests a global regulation mechanism enabling temporary bursts of circular RNAs. 3112 Mar 23


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