• biosynthetic pathway
  • We demonstrate yeast's capacity for biosynthesis of complex plant natural products by reconstructing a de novo noscapine biosynthetic pathway and optimizing noscapine production toward scalable manufacturing. (pnas.org)
  • The noscapine biosynthetic pathway incorporates seven endomembrane-localized plant enzymes, highlighting yeast's ability to functionally express and properly localize large numbers of heterologous enzymes into the endoplasm reticulum. (pnas.org)
  • Here we demonstrate the de novo production of noscapine in Saccharomyces cerevisiae , through the reconstruction of a biosynthetic pathway comprising over 30 enzymes from plants, bacteria, mammals, and yeast itself, including 7 plant endoplasmic reticulum (ER)-localized enzymes. (pnas.org)
  • Many of the enzymes in the noscapine biosynthetic pathway was elucidated by the discovery of a 10 gene "operon-like cluster" named HN1. (wikipedia.org)
  • In 2016, the biosynthetic pathway of noscapine was reconstituted in yeast cells, allowing the drug to be synthesised. (wikipedia.org)
  • Professor Ian Graham, Director of the Centre for Novel Agricultural Products at the University of York, said: "We were amazed to find that this gene cluster encodes for almost the entire biosynthetic pathway for noscapine. (blogspot.com)
  • Plants producing benzylisoquinoline alkaloids have a common biosynthetic pathway, making use of two units of L-tyrosine. (wikipedia.org)
  • derivatives
  • We demonstrated that microbial fermentation can be used to produce halogenated alkaloid derivatives, which can ultimately serve as potential drug leads, through feeding amino acid derivatives to strains. (pnas.org)
  • Noscapine, and its synthetic derivatives called noscapinoids, are known to interact with microtubules and inhibit cancer cell proliferation The lactone ring is unstable and opens in basic media. (wikipedia.org)
  • apoptosis
  • We have previously described a tubulin-binding, natural compound, noscapine, that was nontoxic and triggered apoptosis in many cancer types albeit at 10 μmol/L or higher concentrations depending on the cell type. (aacrjournals.org)
  • We now show that a synthetic analogue of noscapine, 9-bromonoscapine, is ∼10-fold to 15-fold more potent than noscapine in inhibiting cell proliferation and induces apoptosis following G 2 -M arrest in hormone-insensitive human breast cancers (MDA-MB-231). (aacrjournals.org)
  • In this study, we compared chemosensitivity, cell cycle distribution, and apoptosis on noscapine treatment in four cell lines derived from the colorectal carcinoma HCT116 cells: p53 +/+ (p53-wt), p53 −/− (p53-null), p21 −/− (p21-null), and BAX −/− (BAX-null). (aacrjournals.org)
  • Interestingly, despite increased levels of p53, p21-null cells were resistant to apoptosis, suggesting a proapoptotic role of p21 and implying that p53 is a necessary but not sufficient condition for noscapine-mediated apoptosis. (aacrjournals.org)
  • poppies
  • GSK are using this discovery to develop high yielding commercial noscapine poppies in order to establish a reliable route of supply. (blogspot.com)
  • plant
  • Total yield of alkaloids is dependent on light, temperature, the plant species, and the time of harvest (5.2-4). (opioids.com)
  • latex
  • A latex containing several important alkaloids is obtained from immature seed capsules one to three weeks after flowering. (opioids.com)
  • pathway
  • Noscapine titers were improved by 18,000-fold (to low mg/L levels) via a combination of enzyme engineering, pathway and strain engineering, and fermentation optimization. (pnas.org)
  • heroin
  • Noscapine can survive the manufacturing processes of heroin and can be found in street heroin. (wikipedia.org)
  • Noscapine has also been used to identify drug users who are taking street heroin at the same time as prescribed diamorphine. (wikipedia.org)
  • significantly
  • Conversely, loss of p53 and p21 alleles had a counter effect on both BAX and Bcl-2 expression and the p53-null and p21-null cells were significantly resistant to the antiproliferative and apoptotic effects of noscapine. (aacrjournals.org)
  • found
  • Noscapine is metabolised by the body, and is itself rarely found in urine, instead being present as the primary metabolites, cotarnine and meconine. (wikipedia.org)
  • cells
  • Noscapine is currently being investigated as the preferred drug candidate for the clinical trials based on its effectiveness on Heriditary Spastic Paraplegia (HSP) stem cells, safety data, toxicology data, patent status, availability, and future affordability to HSPers. (wikipedia.org)
  • presence
  • medical citation needed] Nausea can be attributed to the presence of noscapine and is more common in first-time or inexperienced users. (wikipedia.org)
  • effects
  • Nausea Vomiting Loss of coordination Hallucinations (auditory and visual) Loss of sexual drive Swelling of prostate Loss of appetite Dilated pupils Increased heart rate Shaking and muscle spasms Chest pains Increased alertness Loss of any sleepiness Loss of stereoscopic vision Noscapine can increase the effects of centrally sedating substances such as alcohol and hypnotics. (wikipedia.org)
  • citation needed] Noscapine should not be taken in conjunction with warfarin as the anticoagulant effects of warfarin may be increased. (wikipedia.org)