SG 2000 / AstraZeneca - LARVOL DELTA

Alkyne modification of DNA cross-linking antitumor agent SJG-136 to monitor induced lesions in cells by click chemistry. (PubMed, Chem Biol Interact) - "Click-SJG-136-induced DNA lesions were revealed via ligation to fluorescent reporters using in situ click chemistry in cells and mouse bone marrow, permitting their detection and quantitation by fluorescence microscopy and flow cytometry. The strategy applied in this study is rapid and could be used for direct pharmacodynamic studies of SJG-136."

Journal • Oncology

Identification of antibody-drug conjugate payloads which are substrates of ATP-binding cassette drug efflux transporters. (PubMed, bioRxiv) - "All the pyrrolobenzodiazepines tested - SJG136, SGD-1882, SG2057, and SG3199 - were substrates of P-gp, ABCG2, and MRP1. The modified anthracyclines nemorubicin and its metabolite PNU-159682 were poorly transported by both ABCB1 and ABCG2 and displayed nanomolar to picomolar toxicity. Further, we found that the efficacy of the recently FDA-approved ADC mirvetuximab soravtansine, which has DM4 as the toxic payload, was decreased in cell lines with overexpression of P-gp. Several commonly used ADC payloads can be effluxed from cells by ABC transporters which may lead to transporter-mediated drug resistance in patients. Future ADCs should be developed using payloads that are not substrates of ABC transporters."

Journal • Oncology • ABCB1 • ABCC1 • ABCG2

Safety assessment of the ethanolic extract of Siparuna guianensis: cell viability, molecular risk predictions and toxicity risk for acute and sub-chronic oral ingestion. (PubMed, J Ethnopharmacol) - "The concentration of 25 μg/mL showed no cytotoxicity. Four molecules were detected in silico did not present a risk of carcinogenicity in female mice, nor mutagenicity, skin sensitization or ocular irritation. In rats, the LD50 is greater than 2,000 mg/kg. Daily oral use for 30 days at up to 800 mg/kg was considered safe, with no significant hematological or histological alterations. These results may support further studies and pre-clinical trials."

Journal • CNS Disorders • Hematological Disorders • Infectious Disease • Migraine • Pain • Respiratory Diseases

Preclinical development of ADCT-212, a PSMA-targeted antibody-drug conjugate employing the pyrrolobenzodiazepine dimer SG2000 for PSMA-expressing cancers (AACR 2023) - "ADCT-212 was tolerated as a single 20 mg/kg dose in male rats, with exposure data being indicative of a linear PK profile with a half-life of approximately 12 days. In conclusion, ADCT-212 demonstrated potent and specific in vitro and in vivo anti-tumor activity while it was stable and well tolerated in the rat, warranting further development of ADCT-212 into the clinic."

Preclinical • Colon Cancer • Genito-urinary Cancer • Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • FOLH1

Preclinical development of ADCT-211, a novel pyrrolobenzodiazepine dimer-based antibody-drug conjugate targeting solid tumors expressing IL13RA2 (AACR 2023) - "ADCT-211 is an antibody-drug conjugate composed of HuCl47, a humanized IgG1 antibody directed against human IL13RA2, site-specifically conjugated using GlycoConnectTM technology to PL1801, which contains HydraspaceTM, a valine-alanine cleavable linker and the PBD dimer cytotoxin SG2000 (drug to antibody ratio ~ 1.8). Expression of membranous IL13RA2 was confirmed by IHC in a panel of primary and refractory GBM samples and malignant melanoma, highlighting them as potential indications for the clinical development of ADCT-211. In conclusion, ADCT-211 demonstrated potent and specific in vitro and in vivo anti-tumor activity and it was stable and well tolerated in the rat, warranting further development of ADCT-211 into the clinic in IL13RA2-expressing cancers."

Preclinical • Adrenal Cortex Carcinoma • Brain Cancer • CNS Tumor • Genito-urinary Cancer • Glioblastoma • Melanoma • Oncology • Renal Cell Carcinoma • Solid Tumor • IL13 • IL13RA2

Chemotherapy-Free Combination of Obinutuzumab and Ibrutinib in First LINE Treatment of Follicular Lymphoma. the Alternative Study By the German Low Grade Lymphoma Study Group (GLSG) (ASH 2018) - "...With this combination a 1-year-PFS of 93% was seen in the GLSG-2000 trial (Hiddemann et al, Blood 2005)...Anticipating the recent reports on a superior activity of obinutuzumab as compared to rituximab in the GALLIUM trial (Marcus et al., NEJM 2017), the GLSG initiated a phase II study combining ibrutinib and obinutuzumab to explore the efficacy and safety of this “chemotherapy-free” alternative...Conclusion s: The chemotherapy – free combination of ibrutinib and obinutuzumab showed high anti-lymyphoma activity with high overall response rates and a high proportion of MRD negativity at one year. While the combination of ibrutinib and obinutuzumab was associated with a low toxicity profile, the combination was inferior to the published results of conventional immunochemotherapies in terms of the primary efficacy endpoint (1-year-PFS).Further evaluations might demonstrate whether subgroups exist which particularly benefit clinically from this low toxicity regime."

Clinical • Biosimilar • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Immunology • Indolent Lymphoma • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology

Differences in the Prevalence and Profile of DSM-IV and DSM-5 Alcohol Use Disorders-Results from the Singapore Mental Health Study 2016. (PubMed, Int J Environ Res Public Health) - "While using the DSM-5 criteria would result in a lower prevalence of AUD in Singapore, it remains a highly comorbid condition associated with a poor health-related quality of life that is largely untreated, which makes it a significant public health concern."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Mental Retardation • Psychiatry

A prospective cohort analysis of residential radon and UV exposures and malignant melanoma mortality in the Swiss population. (PubMed, Environ Int) - "With double the follow-up time, this study confirmed the previously observed association between residential radon exposure and melanoma and non-melanoma skin cancer mortality in Switzerland. Accumulation of radon indoors is preventable and of public health importance."

Journal • Genetic Disorders • Lung Cancer • Melanoma • Non-melanoma Skin Cancer • Skin Cancer • Solid Tumor

A pan-cancer analysis identifies HDAC11 as an immunological and prognostic biomarker. (PubMed, FASEB J) - "In addition, HDAC11 is negatively correlated with the drug sensitivity of oxaliplatin, carmustine, ifosfamide, imexon, lomustine, and BN-2629, indicating the potential synergy between HDAC11 inhibitors and these anti-tumor drugs. HDAC11 is also associated with hallmark pathways, including epithelial mesenchymal transition, IL-6/JAK/STAT3, and allograft rejection pathways. Overall, we provide clues regarding the key role of HDAC11 in multiple cancers."

Biomarker • IO biomarker • Journal • Pan tumor • Immune Modulation • Immunology • Inflammation • Microsatellite Instability • Oncology • Transplant Rejection • HDAC11 • IL6 • MSI • STAT3 • TMB

"Interesting #SpA abstracts #ACR21 0897 Lee et al 🟦 1125 AS pts 🟦 F-up 2001 --> 2018 🟦 Spinal radiographic changes, on average, most pronounced at 30–39 years 🟦However, if preexisting structural damage --> rx progression starts to accelerate from earlier age #ACRambassador" (@Nellziade)

Clinical

Prevalence and patterns of physical activity, sedentary behaviour, and their association with health-related quality of life within a multi-ethnic Asian population. (PubMed, BMC Public Health) - "Age (65 years and above) and income (SGD 2000 to 3999) were associated with a higher likelihood of insufficient physical activity...As insufficient physical activity was associated with poorer physical HRQoL, policymakers should promote moderate physical activity and encouraging the breaking up of prolonged sedentary periods within the middle- and high-income groups, especially at the workplace. Increased leisure-time exercise should be encouraged for those in the lower- income group."

Clinical • HEOR • Journal • Diabetes • Genetic Disorders • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Obesity

Readiness and Acceptance of eHealth Services for Diabetes Care in the General Population: Cross-sectional Study. (PubMed, J Med Internet Res) - "Overall, an unfavorable attitude toward eHealth was observed, with a significantly higher number of participants with diabetes reporting their unwillingness to use these services for their diabetes care. Sociodemographic factors associated with acceptance and readiness identified a group of people who were unlikely to accept the technology and thus need to be targeted for eHealth literacy programs to avoid health care disparity."

Clinical • Journal • Observational data • Diabetes • Metabolic Disorders

Prevalence and Correlates of Social Stigma Toward Diabetes: Results From a Nationwide- Survey in Singapore. (PubMed, Front Psychol) - "Multiple linear regression analyses identified Indian ethnicity (vs. Chinese), higher personal income (≥SGD2000 vs. < SGD 2000) and having close friends or family members who had been diagnosed with diabetes to be significantly associated with lower social distance scores while those aged 50-64 years and those with secondary and vocational education (vs. degree and above) were significantly associated with higher social distance scores... The study found a relatively low level of stigma toward diabetes in the general population of Singapore, although some stigmatizing beliefs emerged. While greater knowledge of diabetes could reduce stigma, anti-stigma messaging should be incorporated into the "War on Diabetes" programme in Singapore."

Journal • Diabetes • Metabolic Disorders

Pharmacophore-based virtual screening for the identification of the novel Src inhibitor SJG-136 against lung cancer cell growth and motility. (PubMed, Am J Cancer Res) - "In conclusion, we have established a pharmacophore-based virtual screening approach to identify novel Src inhibitors that can inhibit lung cancer cell growth and motility through suppressing Src-related pathways. These findings may contribute to the development of targeted drugs for lung cancer treatment, such as lead compounds."

Journal • Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • PXN

Mortality and hospitalization associated to emissions of a coal power plant: A population-based cohort study. (PubMed, Sci Total Environ) - "Results obtained, also when considering multiple sources of exposure, indicate that exposure to CPP emissions represents a risk factor for selected health outcomes as well as the urgently adoption of primary prevention measures and of a specific surveillance programme."

Clinical • Journal