TransThera | 药捷安康’s Post

https://zurl.co/XpsU Could adding a dual tyrosine-regulated kinase 1A inhibitor to GLP-1 drugs be an easy way to regenerate the pancreas?

https://zurl.co/XpsU Could adding a dual tyrosine-regulated kinase 1A inhibitor to GLP-1 drugs be an easy way to regenerate the pancreas?

✨ #Dovitinib is an #Orally Active #RTK Inhibitor for Kinds of #Cancers Research The multi-targeted receptor #tyrosine kinase (#RTK) family includes the receptors for insulin and for many growth factors, such as #EGF, #FGF, #PDGF, #VEGF, and #NGF. RTKs are transmembrane glycoproteins that are activated by the binding of their ligands. When binding to the ligands, it transduces the extracellular signal to the cytoplasm by phosphorylating tyrosine residues on the receptors themselves and on downstream proteins. RTKs regulates #cell #proliferation, #differentiation, #migration, or #metabolic changes, and plays an important role in #cancers. #Dovitinib (#CHIR258) is an #orally active and potent multi-targeted RTK inhibitor, and has potent #antitumor activity in various types of cancer. Dovitinib has a safe and effective pharmacokinetic/pharmacodynamic profile. 📣 #Dovitinib, an orally active and multi-targeted RTK inhibitor, can be used for cancer research. In #vitro, Dovitinib inhibits RTKs with #IC50s of 1-210 nM for #FLT3, c-Kit, #CSF-1R, #FGFR1/FGFR3, #VEGFR1/VEGFR2/VEGFR3, PDGFRα/PDGFRβ, respectively. Dovitinib (12.5-400 nM; 48 h) potently inhibits the FGF-stimulated growth of WT and F384L-FGFR3-expressing B9 cells with an IC50 of 25 nM. Dovitinib (100, 500 nM; 96 h) inhibits FGF-mediated ERK1/2 phosphorylation. It also induces apoptosis of FGFR3-expressing human myeloma cells. Apart from antitumor activity, Dovitinib (0-1 μM, 2 days) also enhances BMP-2-induced osteoblast differentiation (marker: ALP induction). In #vivo: Dovitinib (10-60 mg/kg/day; oral; 21 days) shows significant antitumor effect in a xenograft mouse model of FGFR3 multiple myeloma. And the specific tumor growth inhibition rate is 48%, 78.5%, and 94% respectively. The Ki-67 staining result demonstrates that CHIR-258 inhibits tumor cell growth and induces apoptosis. Dovitinib (50, 75 mg/kg) results in 97% and 98% tumor growth inhibition in a hepatocellular carcinoma #xenograft #mouse #model. In conclusion, Dovitinib, an orally active trosine kinase inhibitor. Dovitinib has antitumor effects and can be used for kinds of cancer research. 👉 https://lnkd.in/grh-gJej 👉 For more detailed information： https://lnkd.in/dQYnQJ5A

POTENTIAL SELECTIVE INHIBITORS OF JANUS KINASE 1 (JAK1): STRUCTURE-ACTIVITY RELATIONSHIP (SAR) Janus kinases (JAKs), a kind of non-receptor tyrosine kinases, the function has been implicated in the regulation of cell proliferation, differentiation and apoptosis, immune, inflammatory response and malignancies. Among them, JAK1 represents an essential target for modulating cytokines involved in inflammation and immune function. Rheumatoid arthritis, atopic dermatitis, ulcerative colitis and psoriatic arthritis are areas where approved JAK1 drugs have been applied for the treatment. In the review, in Bioorganic Chemistry, a brief introduction to JAK1 inhibitors in market and clinical trials has been reported. The structures of high active JAK1 compounds (IC50 ≤ 0.1 nM) were highlighted, with primary focus on structure–activity relationship and selectivity. Moreover, the druggability processes of approved drugs and high active compounds were analyzed. In addition, the issues involved in JAK1 compounds clinical application as well as strategies to surmount these challenges, were discussed. #JAK1 #JanusKinases https://lnkd.in/dt-KJxYx

Choice of Antidiabetic drugs in DM2 based on specific comorbidities ▪︎Metformin ▪︎SU .....sulfonylurea ▪︎SGLT-2-I ..... Sodium-glucose co-transporter-2 inhibitors ▪︎GLP-1 RA ..... (Glucagon-Like Peptide 1 Receptor Agonists) ▪︎DPP-4-I..... (Dipeptidyl Peptidase-4 Inhibitors) ▪︎TZD ...... (Thiazolidinediones) ▪︎Insulin

PRMT5 Target Review: The Next ‘First-in-Class’ Epigenetic Drug? | https://lnkd.in/gCrxHxFP PRMT5 has been a hotly pursued epigenetic target in oncology, but first generation inhibitors displayed intolerable on-target toxicities. The PRMT5:MTA complex has been identified as a “synthetic lethality” target allowing selective inhibition of PRMT5 in MTAP-deleted cancer cells, leading to a renaissance in industry interest. Amgen, Mirati Therapeutics/Bristol Myers Squibb, Tango Therapeutics and AstraZeneca currently have PRMT5:MTA complex stabilizers in the clinic with others close behind in preclinical studies. Our PRMT5 target review outlines why second generation molecules have revived PRMT5, the currently available data for compounds in clinical trials, how they differentiate, and what’s next in the field of PRMT5 inhibitors. We also include the inferred structure of AstraZeneca's undisclosed compound, AZD3470. Read the full article here | https://lnkd.in/gCrxHxFP

Explore one of the most captivating targets in recent research in my opinion: PRMT5. Find out which companies have recently advanced second generation PRMT5 inhibitors into clinical trials, dive into the chemistry of these innovative molecules, and understand how these second generation inhibitors differentiate from the first generation and from each other. I'd love to hear your opinion: What do you think about PRMT5 as a target? Share your thoughts in the comments or DM me :)

PRMT5: the oncology target that came back from the dead. check out our PRMT5 target review which outlines how a deeper understanding of the target biology led to a renaissance in industry interest in this epigenetic target. It includes all the current clinical compounds and data, as well as our inferred structure of AZ's undisclosed clinical compound, AZD3470