Low energy neutral atom imaging on the Moon with the SARA instrument aboard Chandrayaan-1 mission

This paper reports on the Sub-keV Atom Reflecting Analyzer (SARA) experiment that will be flown on the first Indian lunar mission Chandrayaan-1. The SARA is a low energy neutral atom (LENA) imaging mass spectrometer, which will perform remote sensing of the lunar surface via detection of neutral atoms in the energy range from 10 eV to 3 keV from a 100km polar orbit. In this report we present the basic design of the SARA experiment and discuss various scientific issues that will be addressed. The SARA instrument consists of three major subsystems: a LENA sensor (CENA), a solar wind monitor (SWIM), and a digital processing unit (DPU). SARA will be used to image the solar wind-surface interaction to study primarily the surface composition and surface magnetic anomalies and associated mini-magnetospheres. Studies of lunar exosphere sources and space weathering on the Moon will also be attempted. SARA is the first LENA imaging mass spectrometer of its kind to be flown on a space mission. A replica of SARA is planned to fly to Mercury onboard the BepiColombo mission

Novel fulvenes capto-dativelly substituted at C6C_6

A set of four fulvenes bearing both electron-withdrawing and -donating aryl groups at $C_6$ was prepared and shown to be fairly stable, except for the dimerisation of the anisyl-nitrophenyl-fulvene 1a, which also underwent a (4\pi + 2\pi) cycloaddition with C,N-diphenylnitrone

Novel Inhibitors of Nicotinamide-<i>N</i>-Methyltransferase for the Treatment of Metabolic Disorders

Nicotinamide-N-methyltransferase (NNMT) is a cytosolic enzyme catalyzing the transfer of a methyl group from S-adenosyl-methionine (SAM) to nicotinamide (Nam). It is expressed in many tissues including the liver, adipose tissue, and skeletal muscle. Its expression in several cancer cell lines has been widely discussed in the literature, and recent work established a link between NNMT expression and metabolic diseases. Here we describe our approach to identify potent small molecule inhibitors of NNMT featuring different binding modes as elucidated by X-ray crystallographic studies

Novel dual LSD1/HDAC6 inhibitor for the treatment of cancer.

Dually targeting the epigenetic proteins lysine specific demethylase 1 (LSD1) and histone deacetylases (HDACs) that play a key role in cancer cells by modulating gene repressor complexes including CoREST will have a profound effect in inhibiting tumour growth. Here, we evaluated JBI-097 a dual LSD1/HDAC6 inhibitor, for its in vitro and in vivo activities in various tumor models. In vitro, JBI-097 showed a strong potency in inhibiting LSD1 and HDAC6 enzymatic activities with the isoform selectivity over other HDACs. Cell-based experiments demonstrated a superior anti-proliferative profile against haematological and solid tumor cell lines. JBI-097 also showed strong modulation of HDAC6 and LSD1 specific biomarkers, alpha-tubulin, CD86, CD11b, and GFi1b. In vivo, JBI-097 showed a stronger effect in erythroleukemia, multiple myeloma xenograft models, and in CT-26 syngeneic model. JBI-097 also showed efficacy as monotherapy and additive or synergistic efficacy in combination with the standard of care or with immune checkpoint inhibitors. These and other findings suggest that JBI-097 could be a promising molecule for targeting the LSD1 and HDAC6. Further studies are warranted to elucidate the mechanism of action

JBI-097 effect on the modulation of differentiation markers in HEL 92.1.7 cells.

(3A) Effect of JBI-097 on CD11b modulation in HEL 92.1.7 Cells. Cells were treated with 8 concentrations of JBI-097, 10 and 1 μM of JBI-135 (Ricolinostat) and JBI-236 (Iadademstat) for 24h and the mRNA level of CD11b was estimated by RT-qPCR. Error bars indicate mean ± S.E, (3B) Effect of JBI-097 on CD86 modulation in HEL 92.1.7 Cells. Cells were treated with 8 point CRC of JBI-097, 10 and 1 μM of JBI-135 (Ricolinostat) and JBI-236 (Iadademstat) for 24h and the mRNA level of CD86 was estimated by RT-q PCR. Error bars indicate mean ± S.E, (3C) Effect of JBI-097 on Gfi1b modulation in HEL 92.1.7 Cells. Cells were treated with 8 point CRC of JBI-097, 10 and 1 μM of JBI-135 (Ricolinostat) and JBI-236 (Iadademstat) for 24h and the mRNA level of Gfi1b was estimated by RT-q PCR. Error bars indicate mean ± S.E.</p

Anti-proliferative activity of JBI-097 in human erythroleukemia HEL 92.1.7 cells.

Cell proliferation was evaluated using a Alamar Blue assay. Human cell lines (HEL 92.1.7; density, 5 and 10 × 103 for 3 days and 6 days; respectively) were incubated with or without the indicated concentrations of JBI-097, Ricolinostat and Iadademstat for 72 and 144 h. The results shown are representative from two independent experiments.</p

Efficacious of JBI-097 in multiple Xenograft models.

5A: SCID mice were injected s.c. with 5 × 106 HEL 92.1.7 cells and were treated with vehicle, JBI-097 (25 and 50 mg/kg, po, QD), for 14 d.; n = 6 mice per group. 5B: HEL92.1.7 xenograft: Body weight monitored from Day1 to Day14; n = 6 mice per group. 5C: SCID mice were injected s.c. with 5 × 106 MM1.S cells and were treated with vehicle, JBI-097 (12.5 mg/kg, po), Bortezomib (0.5 mg/kg, IP, BIW), Pomalidomide (2.5mg/kg, po, 5x/week), or Bortezomib + JBI-097 or Pomalidomide + JBI-097 for 13 d.; n = 7 mice per group. 5D: MM1.S xenograft: Body weight monitored from Day1 to Day13; n = 7 mice per group. 5E: BALB/c mice were injected s.c. with 1 × 106 CT-26 cells and were treated with vehicle, JBI-097 (20 mg/kg, po), Anti PD-L1 (100μg/animal, IP, Q4D), or Anti PD-L1 + JBI-097 for 14 d.; n = 7 mice per group. 5F: CT-26 syngeneic model: Body weight data from Day1 to Day14; n = 7 mice per group. All data are represented as mean ± SE. In all the studies tumor volume was measured and calculated versus time (days).</p