Selective Cdk4 degrader. Degrades Cdk4 in Molt-4 cells, with no effect on Cdk6 levels. Displays cereblon-dependent degradation. Jiang et al (2019) Development of dual and selective degraders of cyclin-dependent kinases 4 and 6. Angew.Chem.Int.Ed.Engl. 58 6321 PMID:30802347
C24 dihydro Ceramide is a sphingolipid that has been found in the stratum corneum of human skin.[1] It is found in higher concentrations in female sebum compared to male sebum.[2] C24 dihydro Ceramide levels positively correlate with cytotoxicity in CCRF-CEM, MOLT-4, COG-LL-317h, and COG-LL-332h T cell acute lymphoblastic leukemia (ALL) cell lines.[4] Levels of C24 dihydro ceramide are increased by 149.49-fold in dihydroceramide desaturase 1 (DEGS1) knockdown UM-SCC-22A human head and neck squamous carcinoma cells in vitro.[4] C24 dihydro Ceramide levels are also increased in INS-1 β-cells incubated with glucose and palmitate.[5]
KZR-616, a first-in-class inhibitor of the immunoproteasome, selectively targets the LMP7 (IC50: 39/57 nM=hLMP7/mLMP7) and LMP2 (IC50: 131/179 nM=hLMP7/mLMP7) subunits of the immunoproteasome. KZR-616 has the potential for the research of multiple autoimmune diseases[1][2]. KZR-616 also inhibits MECL-1 subunit (IC50=623 nM) and constitutive proteasome β5 subunit (IC50=688 nM). KZR-616 maintains LMP7 and LMP2 selective inhibition in MOLT-4 cells. KZR-616 (250 nM) shows a comparable cytokine inhibition profile peripheral blood mononuclear cells (PBMC)[1].KZR-616 is an immunoproteasome-selective inhibitor identified based on the optimization of ONX-0914 and PR-924 [3]. KZR-616 (5 mg/kg; i.v.; dosing was repeated on days 6, 8, 11, and 13) shows efficacy in the anticollagen antibody induced arthritis (CAIA) model[1]. [1]. Johnson HWB, et al. Required Immunoproteasome Subunit Inhibition Profile for Anti-Inflammatory Efficacy and Clinical Candidate KZR-616 ((2 S,3 R)- N-(( S)-3-(Cyclopent-1-en-1-yl)-1-(( R)-2-methyloxiran-2-yl)-1-oxopropan-2-yl)-3-hydroxy-3-(4-methoxyphenyl)-2-(( S)-2-(2-morpholinoacetamido)propanamido)propenamide). J Med Chem. 2018 Dec 27;61(24):11127-11143. [2]. Muchamuel T, et al. FRI0296 Kzr-616, a selective inhibitor of the immunoproteasome, blocks the disease progression in multiple models of systemic lupus erythematosus (SLE). Annals of the Rheumatic Diseases 2018;77:685. [3]. Xi J, et al. Immunoproteasome-selective inhibitors: An overview of recent developments as potential drugs for hematologic malignancies and autoimmune diseases. Eur J Med Chem. 2019;182:111646.
Nidulin is a depsidone originally isolated from A. nidulans. It is active against the bacteria M. tuberculosis and M. ranoe, as well as the fungi T. tonsurans and M. audouini. It also inhibits the growth of methicillin-resistant S. aureus (MRSA; MIC = 4 μg ml) and has larvicidal activity toward Artemia (LC50 = 2.8 μg ml). Nidulin is cytotoxic to MOLT-3 cells (IC50 = 21.2 μM) but not HuCCA-1, HepG2, or A549 cells (IC50s = >112.7 μM). It inhibits aromatase with an IC50 value of 11.2 μM.
XZ739 is a Cereblon-dependent PROTAC BCL-XL degrader, targeting a member of the Bcl-2 family, with a DC50 value of 2.5 nM in MOLT-4 cells after 16 hours of treatment. Additionally, XZ739 elicits cell death via caspase-mediated apoptosis.
Vercirnon (GSK1605786A) sodium is an orally bioavailable, selective, and potent antagonist of CCR9 . Vercirnon sodium inhibits CCR9-mediated Ca 2+ mobilization and chemotaxis on Molt-4 cells with IC 50 values of 5.4 and 3.4 nM, respectively. Vercirnon sodium is selective for CCR9 over CCR1-12 and CX3CR1-7 (IC 50 s>10 μM for all). Vercirnon sodium is an equipotent inhibitor of CCL25-directed chemotaxis of both splice forms of CCR9 (CCR9A and CCR9B) with IC 50 values of 2.8 and 2.6 nM, respectively.