Gandotinib, also known as LY2784544, is a potent and selective JAK inhibitor. LY2784544 in vitro selectivity for JAK2 was found to be equal or superior to known JAK2 inhibitors. LY2784544 effectively inhibited JAK2V617F-driven signaling and cell proliferation in Ba/F3 cells (IC50=20 and 55 nM, respectively). In vivo, LY2784544 effectively inhibited STAT5 phosphorylation in Ba/F3-JAK2V617F-GFP ascitic tumor cells (TED50=12.7 mg/kg) and significantly reduced (P<0.05) Ba/F3-JAK2V617F-GFP tumor burden in the JAK2V617F-induced MPN model (TED50=13.7 mg/kg, twice daily).
CAT No: R1971
CAS No:1229236-86-5
Synonyms/Alias:LY2784544; LY 2784544; LY-2784544
Chemical Name:3-[(4-chloro-2-fluorophenyl)methyl]-2-methyl-N-(5-methyl-1H-pyrazol-3-yl)-8-(morpholin-4-ylmethyl)imidazo[1,2-b]pyridazin-6-amine
Gandotinib is a small-molecule kinase inhibitor recognized for its potent and selective targeting of the Janus kinase 2 (JAK2) enzyme, a critical component of the JAK-STAT signaling pathway. As a synthetic compound designed to modulate aberrant kinase activity, Gandotinib holds significant value for biochemical investigations into signal transduction, cellular proliferation, and hematopoietic regulation. Its ability to interfere with JAK2-mediated phosphorylation events makes it a versatile tool for researchers aiming to dissect molecular mechanisms underlying cytokine signaling and related pathophysiological processes. The compound's specificity and well-characterized inhibitory profile have established it as a preferred reagent for studies requiring precise modulation of JAK2 activity in both in vitro and cell-based experimental systems.
Signal Transduction Research: Gandotinib is widely utilized in studies focused on elucidating the molecular dynamics of the JAK-STAT pathway. By selectively inhibiting JAK2 kinase activity, it enables researchers to probe the downstream effects of disrupted phosphorylation events in response to cytokine stimulation. This approach is instrumental in mapping the intricate network of protein-protein interactions and transcriptional responses that govern immune cell differentiation, proliferation, and survival. The compound's application in signal transduction assays allows for the identification of novel regulatory nodes and feedback mechanisms within the broader landscape of cytokine-driven cellular processes.
Disease Modeling: In the context of hematopoietic and myeloproliferative disease models, Gandotinib serves as a valuable research agent for simulating conditions of JAK2 dysregulation. Its use in engineered cell lines or primary cell cultures expressing mutant or overactive JAK2 variants provides critical insights into the cellular consequences of persistent kinase signaling. By modulating JAK2 activity, investigators can assess alterations in gene expression profiles, cell cycle progression, and apoptotic responses, thereby advancing the understanding of disease pathogenesis at a molecular level.
Drug Screening and Mechanistic Studies: Gandotinib is frequently incorporated into high-throughput screening platforms and mechanistic assays aimed at evaluating novel therapeutic candidates or combination regimens. Its defined inhibitory action against JAK2 makes it an ideal positive control or comparator compound in studies assessing the efficacy and selectivity of new kinase inhibitors. Furthermore, its use in dose-response and time-course experiments helps delineate the pharmacological parameters governing JAK2 inhibition, supporting the rational design and optimization of next-generation small molecules targeting this pathway.
Biochemical Characterization: The compound is instrumental in the biochemical characterization of JAK2 and its interaction partners. Through in vitro kinase assays, binding studies, and structural analyses, Gandotinib facilitates the quantitative assessment of enzyme kinetics, substrate specificity, and inhibitor binding affinities. These investigations contribute to a deeper understanding of the structural determinants of JAK2 function and inform the development of more selective and potent inhibitors for research applications.
Pathway Validation: Gandotinib is also employed as a reference inhibitor in pathway validation experiments, where its ability to selectively block JAK2 activity serves as a benchmark for confirming the involvement of this kinase in specific cellular phenotypes. By comparing cellular responses in the presence and absence of the inhibitor, researchers can validate the functional relevance of JAK2-mediated signaling events in diverse biological systems. This approach is essential for establishing causal relationships between kinase activity and observed cellular outcomes, thereby strengthening the mechanistic foundation of ongoing research efforts.
1. The spatiotemporal control of signalling and trafficking of the GLP-1R
3. Adipose tissue is a key organ for the beneficial effects of GLP-2 metabolic function
5. TMEM16F and dynamins control expansive plasma membrane reservoirs
If you have any peptide synthesis requirement in mind, please do not hesitate to contact us at . We will endeavor to provide highly satisfying products and services.
Creative Peptides is a trusted CDMO partner specializing in high-quality peptide synthesis, conjugation, and manufacturing under strict cGMP compliance. With advanced technology platforms and a team of experienced scientists, we deliver tailored peptide solutions to support drug discovery, clinical development, and cosmetic innovation worldwide.
From custom peptide synthesis to complex peptide-drug conjugates, we provide flexible, end-to-end services designed to accelerate timelines and ensure regulatory excellence. Our commitment to quality, reliability, and innovation has made us a preferred partner across the pharmaceutical, biotechnology, and personal care industries.
Read More