dexloxiglumide (CR2017) / Viatris - LARVOL DELTA

Drug Solubility in Human Colonic Fluids and Comparison to Small Intestinal and Simulated Fluids. (PubMed, Mol Pharm) - "Therefore, this study aimed to measure and compare the apparent solubility of eight drugs with varying physicochemical properties (apixaban, danoprevir, dexloxiglumide, febuxostat, fenofibrate, rofleponide, ticagrelor and tofacitinib) in pooled aspirates from the proximal human colon and small intestine, along with simulated media and buffers commonly used in solubility assessment. Solubilities of all other drugs were predicted reasonably well in blank buffers and simulated media. The results generated in this study may serve as reference data for the validation of improved in vitro and in silico tools for colonic drug solubility prediction."

Journal • Gastrointestinal Disorder

Acute effects of foam roller or stick massage on indirect markers from exercise-induced muscle damage in healthy individuals: A systematic review and meta-analysis. (PubMed, J Bodyw Mov Ther) - "In conclusion, the current literature appears to not support the advantage of foam roller or stick massage to improve recovery of muscle damage indirect markers (muscle soreness, range of motion, muscle swelling, and maximal voluntary isometric contraction) compared to a non-intervention control group in healthy individuals. Furthermore, due to the heterogeneity of the methodological designs among the included studies, making it difficult to compare the results. In addition, there are not enough high-quality and well-designed studies on foam roller or stick massage to draw any definite conclusions."

Journal • Retrospective data • Review • Musculoskeletal Pain

EARLY IN VIVO GENERATION OF VΓ9VΔ2 T CELLS AFTER HAPLOIDENTICAL STEM CELL TRANSPLANT WITH POST-TRANSPLANT CYCLOPHOSPHAMIDE: A MONOCENTRIC PHASE 1 STUDY (EBMT 2023) - P1 | "These cells, that kill tumor cells in a non-MHC restricted manner and do not induce graft-versus-host disease (GVHD) can be generated by stimulation with bisphosphonate zoledronic acid (ZA), in combination with interleukin-2 (IL-2)...Inclusion criteria were patients (pts) between 18-70 years old with a hematological disease eligible for haplo-SCT using a Baltimore-based conditioning with fludarabine (Luznik, BBMT, 2008) or clofarabine (Chevallier, Oncotarget, 2018), pts with no HLA-matched sibling or unrelated donor, ECOG status <2, no contra-indication to ZA nor IL-2 and informed consent... Early in vivo generation of Vγ9Vδ2 T cells is possible after haplo-SCT with PTCY by using a combination of ZA and repeated IL-2 infusions. The MTD was not reached. This study lays the groundwork for future phase 2/3 studies, with the hope to document lesser post-transplant relapse with this particular adaptive immunotherapy."

P1 data • Post-transplantation • Preclinical • Acute Graft versus Host Disease • Bone Marrow Transplantation • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Disorders • Immunology • Infectious Disease • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

Phase I study of fibroblast growth factor receptor 2 antibody-drug conjugate (FGFR2-ADC) BAY 1187982 in patients with advanced cancer (AACR 2017) - "Background: FGFR2-ADC (BAY 1187982) consists of an anti-FGFR2 antibody (BAY 1179470) and a stably linked, highly potent and non-cell permeable microtubule-binding auristatin toxophore. While this drug was tolerated well at lower dose levels, dose-limiting toxicities occurred below the expected therapeutic dose level. As the predicted human efficacious dose level based on the majority of animal models was above 0.4 mg/kg (Wittemer-Rump et al. AACR; Cancer Res 2015;75, 15 Suppl: Abstract nr 1683) a Phase II dose cannot be recommended and a successful clinical development of the compound was regarded as unlikely."

P1 data • Biliary Cancer • Biosimilar • Breast Cancer • Gastrointestinal Cancer • Oncology • Ophthalmology • Renal Disease • Venous Thromboembolism

BMS-986205, an optimized indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor, is well tolerated with potent pharmacodynamic (PD) activity, alone and in combination with nivolumab (nivo) in advanced cancers in a phase 1/2a trial (AACR 2017) - "AACR 2017 [abst 6774]). BMS-986205 is an optimized, once-daily, selective and potent oral IDO1 inhibitor at clinically relevant concentrations. It is well tolerated up to at least 200 mg in combination with nivo in this novel trial. Evidence of substantial serum kyn reduction was observed at doses as low as 25 mg QD; inhibition at 100 and 200 mg QD appears greater than that reported for other in-class compounds."

P1/2 data • Biosimilar • Immunology • Oncology • Renal Disease

An Increased Aspartate to Alanine Aminotransferase Ratio Is Associated With a Higher Risk of Cognitive Impairment. (PubMed, Front Med (Lausanne)) - "In this 7-year longitudinal follow-up study, we found that a higher AST/ALT ratio was a risk factor for future development of aMCI (p = 0.006, HR = 2.247, 95%CI: 1.248∼4.049), and the AST/ALT ratio was negatively correlated with right hippocampal volume (r = -0.148, p = 0.043). An increased ratio of AST to ALT is associated with a higher risk of cognitive impairment and may impair cognitive function by affecting hippocampal volume."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Metabolic Disorders

A phase II trial of the FGFR inhibitor pemigatinib in patients with metastatic esophageal-gastric junction/gastric cancer trastuzumab resistant: the FiGhTeR trial. (PubMed, Ther Adv Med Oncol) - "CRC2017_02. 2017-004522-14."

Clinical • Journal • P2 data • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • FGF • FGFR3

"Speaking at @AACR #AACR2017 on a new #cetuximab resistance in #colorectalcancer. APR 4 @3:20 Room 206 - Level 2 #WashingtonConventionCenter" - bhumi_singh

Biosimilar • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Twitter

A high-quality genome assembly of quinoa provides insights into the molecular basis of salt bladder-based salinity tolerance and the exceptional nutritional value. (PubMed, Cell Res) - "Epidermal salt bladder cells exhibit similar characteristics as trichomes, with a significantly higher expression of genes related to energy import and ABA biosynthesis compared with the leaf lamina. The quinoa genome sequence provides insights into its exceptional nutritional value and the evolution of halophytes, enabling the identification of genes involved in salinity tolerance, and providing the basis for molecular breeding in quinoa.Cell Research advance online publication 10 October 2017; doi:10.1038/cr.2017.124."

Journal • Biosimilar

SPSB1-mediated HnRNP A1 ubiquitylation regulates alternative splicing and cell migration in EGF signaling. (PubMed) - Cell Res - "Mechanistically, EGF-induced ubiquitylation of hnRNP A1 together with the activation of SR protein kinases (SRPKs) results in the upregulation of a Rac1 splicing isoform, Rac1b, to promote cell motility. These findings unravel a novel crosstalk between protein ubiquitylation and alternative splicing in EGF/EGF receptor signaling, and identify a new EGF/SPSB1/hnRNP A1/Rac1 axis in modulating cell migration, which may have important implications for cancer treatment.Cell Research advance online publication 13 January 2017; doi:10.1038/cr.2017.7."

Journal • Biosimilar • Oncology

"#CRT2017 how to start on #SoMe #ACCFIT #ACCEarlyCareer #ACCIC #AHA17 #EuropCR @chadialraies @DrSheilaSahni https://t.co/l0FubZfVrZ"

Biosimilar

YTHDF3 facilitates translation and decay of N(6)-methyladenosine-modified RNA. (PubMed) - Cell Res - "These results indicate that together with YTHDF1 and YTHDF2, YTHDF3 plays critical roles to accelerate metabolism of m(6)A-modified mRNAs in the cytoplasm. All three YTHDF proteins may act in an integrated and cooperative manner to impact fundamental biological processes related to m(6)A RNA methylation.Cell Research advance online publication 20 January 2017; doi: 10.1038/cr.2017.15."

Journal • Biosimilar

Cryo-EM structure of human ATR-ATRIP complex. (PubMed, Cell Res) - "The catalytic pockets face outward and substrate access is not restricted by inhibitory elements. Our studies provide a structural basis for understanding the assembly of the ATR-ATRIP complex and a framework for characterizing ATR-mediated DNA repair pathways.Cell Research advance online publication 22 December 2017; doi:10.1038/cr.2017.158."

Journal

Structural basis for specific flagellin recognition by the NLR protein NAIP5. (PubMed, Cell Res) - "The extreme C-terminal side of the flagellin is anchored to a sterically constrained binding pocket of NAIP5, which likely acts as a structural determinant for discrimination of different bacterial flagellins by NAIP5, a notion further supported by biochemical data. Taken together, our results shed light on the molecular mechanisms underlying NLR ligand perception.Cell Research advance online publication 28 November 2017; doi:10.1038/cr.2017.148."

Journal

Landscape of the regulatory elements for lysine 2-hydroxyisobutyrylation pathway. (PubMed, Cell Res) - "Our study has thus discovered both the "writers" and "erasers" for histone Khib marks, and major Khib protein substrates. These results not only illustrate the landscape of this new lysine acylation pathway, but also open new avenues for studying diverse functions of cellular metabolites associated with this pathway.Cell Research advance online publication 1 December 2017; doi:10.1038/cr.2017.149."

Journal