iSONEP (sonepcizumab) / Pfizer, Apollo Endosurgery - LARVOL DELTA

2- and 3-Fluoro-3-deaza-1',6'-isoneplanocin: synthesis and antiviral properties (including Ebola and Marburg). (PubMed, Bioorg Med Chem Lett) - "Target 12 displayed significant activity towards 5 viruses (μM): H1N1 (EC 357, SI >1000), hepatitis B virus (EC 1.28, CC >357, SI >279), norovirus (EC 0.64, CC >357, SI >558), Ebola (EC 100, SI >1000), and Marburg (EC 100, SI >1000). On the other hand, while 11 showed limited antiviral effects, its toxicity was significant, precluding any further usefulness."

Journal • Hepatitis B • Hepatology • Infectious Disease • Inflammation

Relationship between Depressive Symptoms and Weather Conditions. (PubMed, Int J Environ Res Public Health) - "The findings of our study suggest that some levels of weather variables have a statistically significant effect on DS."

Journal • CNS Disorders • Depression • Psychiatry

Targeting Sphingolipids for Cancer Therapy. (PubMed, Front Oncol) - "Several inhibitors or activators of sphingolipid signaling, such as fenretinide, safingol, ABC294640, ceramide nanoliposomes (CNLs), SKI-II, α-galactosylceramide, fingolimod, and sonepcizumab, have been described. In the case of CNLs, SKI-II, fingolimod and sonepcizumab there are some limitations and absence of enough clinical studies to demonstrate a benefit. The effectiveness or lack of a major therapeutic effect of sphingolipid modulation by some drugs as a cancer therapy and other aspects related to their mechanism of action are discussed in this review."

Journal • Review • Hepatology • Oncology

Inhibition of sphingosine 1-phosphate protects mice against chondrocyte catabolism and osteoarthritis. (PubMed, Osteoarthritis Cartilage) - "Lack of S1P in myeloid cells and local S1P neutralization alleviates from osteoarthritis in mice. These data identify S1P as a therapeutic target in OA."

Journal • Preclinical • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology • MMP13

Synthesis of D-like and L-like 5'-fluoro-5'-deoxy-1',6'-isoneplanocins and their antiviral activity including Ebola. (PubMed, Nucleosides Nucleotides Nucleic Acids) - "Antiviral evaluation found D-like 5'-fluoro-5'-deoxy-1',6'-isoneplanocin to display less broad-spectrum antiviral effects than the parent D-like including weaker activity against Ebola and norovirus. The L-like enantiomer was devoid of any activity, contrary to the parent L-like compound."

Journal • Infectious Disease

Enantiomeric 4'-Truncated 3-deaza-1',6'-isoneplanocins: Synthesis and antiviral properties including Ebola. (PubMed, Bioorg Med Chem Lett) - "It is to be noted that 7b showed no effects on this enzyme and 8b was minimally inhibitory. These results offer preliminary insight into the differing mechanisms of action of D- and L- like structures and enlighten structural features to guide additional antiviral agent pursuit in the isoneplanocin series."

Journal • Cytomegalovirus Infection • Infectious Disease

l-like 3-deazaneplanocin analogues: Synthesis and antiviral properties. (PubMed, Bioorg Med Chem Lett) - "The potent antiviral properties of 3-deazaneplanocin, 3-deaza-isoneplanocins (1) and recently discovered l-like carbocyclic nucleosides (2, 3 and 4) prompted us to pursue rationally conceived l-like 3-deazaneplanocin analogues...Antiviral analysis found 5 and 6 to display favorable activity against the Ebola virus, as expected for 3-deazaadenine carbocyclic nucleosides. Compound 5 also showed activity against arenaviruses, including Pinchinde and Tacaribe."

Journal • Infectious Disease

5'-Nor-3-Deaza-1',6'-Isoneplanocin, the Synthesis and Antiviral Study. (PubMed, Molecules) - "Antiviral assays showed activity against the JC virus (EC = 1.12 µM for (4'R)-8; EC = 59.14 µM for (4'S)-7) and inactivity of both compounds against several DNA and RNA viruses. Both compounds lacked cytotoxicity."

Journal

[VIRTUAL] Synthesis of 5′-nor-isoneplanocin analogues as antiviral agents (ACS-Fall 2020) - "Nucleosides and nucleotides are building blocks of the genetic material for viruses and their chemical structure analogues are important resources in search for antiviral agents, such as Remdesivir and Galidesvir for ongoing COVID-19 pandemic.3-Deazaneplanocin (1) and 3-deazaisoneplanocin (2) have been recognized with board spectrum antiviral activity including against the Ebola viruses. This makes the designed 5′-nor-isoneplanocin structures (4 and 5) not only interesting derivatives of 2, but also surrogates to 3A novel synthetic approach to 4 and 5 was developed with a propylidene rearrangement as the key step. Targets 4and its 4′-epimer 5 were accomplished and their L-enantiomers are forthcoming."

Infectious Disease • Novel Coronavirus Disease

Sphingosine-1-phosphate signalling drives an angiogenic transcriptional programme in diffuse large B cell lymphoma. (PubMed, Leukemia) - "Importantly, S1PR1 functional antagonists, including Siponimod, and the S1P neutralising antibody, Sphingomab, inhibited S1P signalling in DLBCL cells in vitro. Furthermore, Siponimod, also reduced angiogenesis and tumour growth in an S1P-producing mouse model of angiogenic DLBCL. Our data define a potential role for S1P signalling in driving an angiogenic gene expression programme in the tumour vasculature of DLBCL and suggest novel opportunities to target S1P-mediated angiogenesis in patients with DLBCL."

Journal • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Lpath adds 2 Patents to growing Portfolio of Antibody Therapeutics (Beaconequity) - Lpath plans an ASONEP phase 2 trial in renal cell carcinoma patients next year

Anticipated P2 initiation • Renal Cell Carcinoma

Both enantiomers of 6'-Isoneplanocin. (PubMed, Nucleosides Nucleotides Nucleic Acids) - "Both products were evaluated against a number of DNA and RNA viruses and found to be inactive. This observation is suggested to be due to the displacement of the C-4' hydroxymethyl of neplanocin (in the D-like form) away from the lysine425 of S-adenosylhomocysteine hydrolase, which is important for inhibition by neplanocin and, in turn, its antiviral activity."

Journal • Biosimilar

A Phase 2 Study of ASONEP™ to Treat Unresectable and Refractory Renal Cell Carcinoma (clinicaltrials.gov) - P2; N=39; Active, not recruiting; Sponsor: Lpath, Inc.; Recruiting -> Active, not recruiting ; Trial primary completion date: Dec 2014 ->Dec 2015

Enrollment closed • Biosimilar • Oncology • Renal Cell Carcinoma

Ion Binding Properties of a Naturally Occurring Metalloantibody. (PubMed, Antibodies (Basel)) - "We crystallized and determined the X-ray crystal structure of the LT1009 Fab fragment in 10 mM CaCl and found that it binds two Ca in a manner similar to its antigen-bound state. To test this hypothesis, we engineered, expressed, and purified a Fab fragment consisting of naïve murine germline-encoded light and heavy chain genes from which LT1002 is derived and observed that it binds Ca in solution. We propose that LT1002 is representative of a class of naturally occurring metalloantibodies that are evolutionarily conserved across diverse mammalian genomes."

Journal

Inflammatory Conditions Disrupt Constitutive Endothelial Cell Barrier Stabilization by Alleviating Autonomous Secretion of Sphingosine 1-Phosphate. (PubMed, Cells) - "Constitutive barrier stability of HUVEC, but not EA.hy926, was significantly compromised by the S1PR1 antagonist W146 and by the anti-S1P antibody Sphingomab...Our work suggests a new mechanism for barrier integrity maintenance. Secretion of S1P by EC via Spns2 contributed to constitutive EC barrier maintenance, which was disrupted under inflammatory conditions via the down-regulation of the S1P-transporter Spns2."

Journal • Immunology • Infectious Disease • Septic Shock