S134 Kinase Selectivity Profiles Of Nintedanib And Imatinib

Abstract

MethodsIn this cross-sectional study, demographics, medication and spirometry were prospectively recorded from patients attending a secondary care asthma clinic who were also genotyped and completed the Asthma Control Questionnaire (ACQ-6). Results A total of 223 patients prescribed ICS were included in the analysis. Overall mean age was 46 years, FEV 1 86%, median ICS dose 800 mg/day and 73% were prescribed LABA. There were no differences in terms of spirometry and ACQ-6 between the three genotypes (Table 1). In patients who were prescribed LABA there was no difference in ACQ-6 comparing patients with no Arg copies (n = 80, ACQ-6 1.82) versus those with one or two Arg copies (n = 83, ACQ-6 1.70). Moreover salbutamol reliever use was no different. Conclusion Gly16Arg polymorphism was not associated with impaired asthma control in ICS treated adult asthmatics irrespective of LABA exposure. REFERENCES1 Basu K, Palmer CN, Tavendale R, Lipworth BJ, Mukhopadhyay S. Adrenergic beta (2)-receptor genotype predisposes to exacerbations in steroid-treated asthmatic patients taking frequent albuterol or salmeterol.

Pharmacological treatment for connective tissue disease-associated interstitial lung involvement: Protocol for an overview of systematic reviews and meta-analyses

“…Nevertheless, the impact of individual therapies in CTD-ILD seems to be more complex and not solely limited to targeted immunomodulatory or profibrotic pathways [ 36 , 37 , 40 ]. This is especially true for certain tyrosine kinase inhibitors which have shown inconsistent results in the treatment of ILDs despite having partially overlapping inhibition profiles [ 41 ]. Hence, the treatment categories may not necessarily reflect the clinically relevant effects of the individual drugs.…”

Pharmacological treatment for connective tissue disease-associated interstitial lung involvement: Protocol for an overview of systematic reviews and meta-analyses

“…Nevertheless, the impact of individual therapies in CTD-ILD seems to be more complex and not solely limited to targeted immunomodulatory or profibrotic pathways (36, 37, 40). This is especially true for certain tyrosine kinase inhibitors which have shown inconsistent results in the treatment of ILDs despite having partially overlapping inhibition profiles (41). Hence, the treatment categories may not necessarily reflect the clinically relevant effects of the individual drugs.…”

Development of a Ligand-Targeted Therapeutic Agent for Neurokinin-1 Receptor Expressing Cancers

“…Synthesis of NK1RL-SPL-S-S-TubBH (6). To a solution of NK1RL-SPL (4, 4.0 mg, 4.024 μmol) in dry DMSO (0.1 mL) at 0 °C was added disulfide-activated TubBH (4.4 mg, 4.024 μmol) followed by DIPEA (11 μL, 80.48 μmol) under argon atmosphere.…”

“…With interest in precision medicine steadily increasing, enhanced emphasis has been placed on the design and development of tumor-targeted therapeutics . Highly selective enzyme inhibitors have received the greatest attention, probably due to the remarkable success of imatinib, an inhibitor of the fusion protein, BCR-Abl, that drives malignancy in chronic myelogenous leukemia. , Although imatinib is now known to also inhibit other tyrosine kinases, − its relative specificity for BCR-Abl and associated minimal systemic toxicity has inspired the search for additional “tumor-targeted” drugs that similarly suppress proliferation of cancer cells without significantly harming healthy cells. This search has led to the exploration of tumor-specific targeting ligands for delivery of attached chemotherapeutic agents to malignant cells in the anticipation that tumor-selective conveyance of a chemotherapeutic agent will further reduce its toxicity to healthy cells. , Examples of such ligand-targeted therapeutic agents undergoing clinical trials or already FDA-approved include both antibody–drug conjugates and low molecular weight ligand-targeted drugs. − …”