T1540

Doxepin hydrochloride (Aponal) is a dibenzoxepin tricyclic compound. It displays a range of pharmacological actions including maintaining adrenergic innervation. Its mechanism of action is not fully understood, but it appears to block reuptake of monoaminergic neurotransmitters into presynaptic terminals. It also possesses anticholinergic activity and modulates antagonism of histamine H(1)- and H(2)-receptors.

GNE-0723 is a selective positive allosteric modulator of the NMDA receptor, with an EC50 of 21 nM for GluN2A. It can cross the blood-brain barrier (BBB) and improve outcomes in Dravet syndrome (DS) and Alzheimer's disease (AD).

(Iso)-GNE-0723 is an isomer of GNE-0723, widely used in biochemical experiments and drug synthesis research. GNE-0723 is a blood-brain barrier-permeable positive modulator of the NMDAR.

GNE-5729 is a positive allosteric modulator of NMDAR with the advantage of crossing the blood-brain barrier and being orally available, with EC50 values of 37 nM, 4.7 μM and 9.5 μM for GluN2A, GluN2C and GluN2D, respectively, and can be used for the study of neurological and psychiatric disorders.

(S,S)-GNE 5729 is an enantiomer of GNE 5729, widely used in biochemical experiments and drug synthesis research. GNE 5729 is a blood-brain barrier-permeable positive modulator of the NMDAR.

GNE-272 is a potent and highly selective inhibitor of the CBP/EP300 bromodomains. This product inhibits CBP and EP300 with IC50 values of 0.02 μM and 0.03 μM, respectively, exhibiting 650-fold selectivity over BRD4 (IC50 = 13 μM). In cell-based assays, it effectively inhibits MYC expression (EC50 = 0.91 μM) without significant off-target activity against various kinases, receptors, or cytochrome P450 isoforms. As a selective in vivo probe, GNE-272 serves as a vital pharmacological tool for studying CBP/EP300 functions in acute myeloid leukemia (AML) and other cancers.

GNE-4997 is a potent and selective inhibitor of the interleukin-2-inducible T-cell kinase (Ki: 0.09 nM). The correlation between the basicity of solubilizing elements in GNE-4997 and off-target antiproliferative effects reduces cytotoxicity.

GNE-618 is a potent and orally active inhibitor of nicotinamide phosphoribosyltransferase (IC50: 6 nM). GNE-618 depletes NAD levels and induces tumor cell death. It has anti-tumor activity.

GNE-6468 is a potent and selective agonist of RORγ(RORc) (EC50: 13 nM for HEK-293 cell).

GNE-781 is a highly potent and selective inhibitor of CBP (IC50: 0.94 nM in TR-FRET assay). GNE-781 also inhibits BRET and BRD4(1) (IC50s: 6.2 nM and 5100 nM, respectively).

GNE-955 is a potent and orally active inhibitor of pan Pim kinase, with inhibition constants (Kis) of 0.018 nM, 0.11 nM, and 0.08 nM for Pim1, Pim2, and Pim3, respectively.

GNF179, an optimized 8,8-dimethyl IP analog, exhibits potency (4.8 nM against the multidrug-resistant strain W2), in vitro metabolic stability, and in vivo oral bioavailability.