First reported nonpeptidomimetic agonist on the G protein-coupled chemokine receptor CXCR-3

A peptidic glucagon like peptide 2 (GLP-2) analogue for treatment of type2 diabetes..

MTK458 (MTK-458) is a potent, selective and brain penetrant PINK1 activator, MTK-458 promotes the first step in mitophagy. MTK458 selectively activates PINK1 by stimulating dimerization and stabilization of the PINK1/TOM complex. MTK458 binds to PINK1 and stabilizes an active heterocomplex, thereby increasing mitophagy. MTK458 reduces the PINK1 substrate pS65-Ubiquitin (pUb) in primary neurons and in vivo. MTK458 drives clearance of pathologic α-synuclein in vitro and in vivo, decreases pS129 α-synuclein aggregates and normalized both brain and corresponding plasma pUb levels in both cellular and animal models of α-synuclein aggregation (PD-like pathology).

BMS-986172 is a highly Potent MGAT2 Inhibitor that Achieved Targeted Efficacious Exposures at a L BMS-986172 showed on-target- and mechanism-based pharmacology. Moreover, its favorable pharmacokinetic (PK) profile and the lack of species variability in the glucuronidation potential resulted in a greater confidence level in the projection of a low dose for achieving targeted efficacious exposures in humans. Consistent with these projections.

TAK-994 is an oral, selective OX2R agonist developed by Takeda for the treatment of narcolepsy type 1 (with cataplexy) and type 2 (without cataplexy). The molecule follows Takeda’s previous clinical molecule, TAK-925 (danavorexton), which was the first OX2R agonist to be tested in people with NT1 but had poor oral bioavailability and was administered intravenously in the clinic.

KIO-301 – A photoswitchable HCN channel blocker with positive initial results from a Phase I/II for retinitis pigmentosa and choroideremia study that is being developed by KIORA Therapeutics.

TL13-12 is a novel Anaplastic Lymphoma Kinase (ALK)-PROTAC developed through conjugation of TAE684 and the cereblon ligand pomalidomide.

Ebio1 is a selective voltage-gated potassium channel KCNQ2 activator. Ebio1 activates KCNQ2 by generating an extended channel gate with greater conductance at a saturation voltage (+50 mV).

SMD-3040 is a potent and selective SMARCA2 degrader with DC50 of 12 nM and demonstrates an excellent degradation selectivity for SMARCA2 over SMARCA4. SMD-3040 achieves strong tumor growth inhibition in two SMARCA4-deficient xenograft models at well-tolerated dose schedules.

NP3-562 is a potent, orally bioavailable, tricyclic NLRP3 inhibitor with IC50 of 0.26 μM in the FP binding assay. NP3-562 demonstrates excellent potency in human whole blood and full inhibition of IL-1β release in a mouse acute peritonitis model.

mPEG-DMG, MW 5,000 is a large PEG lipid containing a DMG group and a methoxy cap. The methoxy cap is inert while the DMG group is a popular ligand for developing PEG-lipids and lipid nanoparticles more broadly. Varying the size of a PEG linker greatly impacts its molecular dynamics, thereby affecting DMPK and ADME properties of a given API.

CBI1 (covalent BAX inhibitor 1) is a compound that selectively derivatizes BAX at C126 with BME50 value of 905 μM. CBI1 inhibits BAX activation by triggering ligands or point mutagenesis.

LY3130481 (CERC611) is a potent, selective, noncompetitive TARP γ8-associated AMPA receptors with IC50 of 65.3 nM (GluA1/TARP γ-8), with no activity for γ-2 (cerebellum) or other TARP members.

DCAF1-BRD9 PROTAC DBr-1 potently degrades BRD9 with a DC50 of 90 nM but only weakly affected BRD7 protein levels. DBr-1 provides an alternative strategy to tackle intrinsic resistance to VHL-degrader.

CPI-0610 is a small molecule inhibitor of the Bromodomain and Extra-Terminal (BET) family of proteins, with potential antineoplastic activity. Upon administration, the BET inhibitor CPI-0610 binds to the acetylated lysine recognition motifs on the bromodomain of BET proteins, thereby preventing the interaction between the BET proteins and acetylated histone peptides. This disrupts chromatin remodeling and gene expression. Prevention of the expression of certain growth-promoting genes may lead to an inhibition of tumor cell growth.

Protein E7(43-62) is an E7-derived peptide with anti-tumor effects (short peptide spanning the 43th to 62th amino acid residues in the E7 protein).

CMX990 is a novel covalent SARS-CoV-2 3CL protease inhibitor with EC50 of 10 nM, and shows good oral bioavailability and tolerability in preclinical species. Compared with nirmatrelvir, CMX990 has distinctly differentiated potency (~5-fold more potent in primary cells) and human in vitro clearance (>4-fold better microsomal clearance and >10-fold better hepatocyte clearance), with good in vitro-to-in vivo correlation.

Doxorubicin free base, also called doxorubicin, is an anthracycline antibiotic with antineoplastic activity. Approved API for cancer therapeutic use is doxorubicin HCl. Doxorubicin, isolated from the bacterium Streptomyces peucetius var. caesius, is the h

AMT hydrochloride is a selective inhibitor of inducible NOS (iNOS) with Ki of 4.2 nM.

AI-10-104 is a small molecule inhibitor that interferes with CBFβ binding to RUNX proteins with IC50 of 1.25 uM in FRET assays.

JP-11646 is a novel potent, selective, non-ATP competitive Pim2 inhibitor with IC50 of 0.5/1/24 nM for Pim2/3/1, respectively; shows less potency for other kinases in a kinase selectivity panel; exhibits 4-760-fold greater suppression of MM proliferation and viability than ATP-competitive PIM inhibitors; significant reduces tumor burden and increases median survival in xenogeneic myeloma murine models.

ZNL-0056 is an ATP-competitive inhibitor that targets both the Cys797 and Cys775 in the ATP binding site of EGFR, which is the first compound capable of targeting a nonconserved and partially buried Cys775.

ARUK2001607 is a potent, selective and brain penetrant PI5P4Kγ inhibitor with binding KD of 7.1 nM, pIC50 of 7.1 (PI5P4Kγ+).

Mosnodenvir (JNJ-1802) is an orally active pan serotype dengue virus (DENV) inhibitor, with EC50 values ranging from 0.057 to 11 nM for four dengue virus (DENV) serotypes. Mosnodenvir blocks viral replication by inhibiting the formation of complexes between two viral proteins, nonstructural protein 3 (NS3) and NS4B, thereby preventing the formation of new viral RNA. Mosnodenvir exhibits picomolar to nanomolar antiviral activity in vitro and has antiviral efficacy in mice and non-human primates.

TD-1473 (Izencitinib, TD1473, JNJ 8398) is a potent, selective, oral gut-selective pan-JAK inhibitor with pKi of 10.0/10.0/8.8/9.5 for human recombinant JAK1, JAK2, JAK3 and TYK2.TD-1473 inhibited cytokine-induced phosphorylation of STAT1 in mouse primary colonic epithelial cells with pIC50 values for inhibition against IL-6, IFNα and IFNγ were 7.3, 6.8 and 7.0.TD-1473 demonstrated JAK inhibitory activity in ex vivo mouse colon and human IBD patient colonic tissue. TD-1473 (Izencitinib) is under development for the treatment of ulcerative colitis.

E722-2648 (Compound C-1) is a novel specific and competitive small molecule β-catenin/BCL9 interaction inhibitor with ITC KD of 1.05 uM and IC50 of 9 uM, blocks oncogenic Wnt signaling and disrupts cholesterol homeostasis in colorectal cancer.E722-2648 (Compound C-1) inhibited β-catenin/BCL9 complexes at concentrations as low as 1 uM in BCL9-dependent CRC cell lines, Colo320 and HCT116.E722-2648 (Compound C-1) inhibited the expression of bona fide downstream Wnt/β-catenin target genes, AXIN2 and CD44, in the β-catenin/BCL9-dependent CRC cell lines.E722-2648 (Compound C-1) disrupted cholesterol homeostasis via increased cholesterol esterification and lipid droplet accumulation.E722-2648 (Compound C-1) demonstrated antitumorigenic activity in CRC cell lines and xenograft mouse models.

NCGC 00067819 is a small molecule compound that potentiates CREB signaling with EC50 of 16 nM in the primary screen and 79 nM in the CHO CRE-β-lactamase confirmation assay.

VK-II-86 is a carvedilol analogue lacking antagonist activity at β-adrenoceptors, effectively suppresses SOICR by directly reducing the open duration of the cardiac ryanodine receptor (RyR2).VK-II-86 exhibited >2,000-fold lower beta-AR binding affinity than carvedilol.VK-II-86 prevented stress-induced ventricular tachyarrhythmias in RyR2-mutant mice and did so more effectively when combined with either of the selective beta blockers metoprolol or bisoprolol.VK-II-86 prevented hypokalaemia-induced AP prolongation and depolarization but did not alter AP parameters in normokalaemia.

Novel glucocerebrosidase activator; Non-inhibitory chaperones of glucocerebrosidase

Benzamide is a small molecule Magmas inhibitor (SMMI). Magmas is mitochondria associated，granulocyte-macrophage colony stimulating factor signaling molecule，as well as a GM-CSF inducible gene in myeloid cells. Magmas-IN-1 inhibits Magmas and modulates mitochondrial function. Magmas-IN-1 also inhibits proliferation in yeast at 4 μM.