A potent, selective hERG potassium channel (Kv11.1) activator.

A potent, selective FLAP inhibitor with binding IC50 of 2.6 nM; inhibits LTB4 synthesis following ionophore challenge in human whole blood with IC50 of 76 nM (5 h incubation); shows good selectivity over CYP3A4, 2C9, and 2D6; exhibits excellent preclinical toxicology, pharmacokinetics and oral bioactivity.

A potent, selective CCR5 antagonist and HIV-1 entry inhibitor.

A potent, selective CCR5 antagonist and HIV-1 entry inhibitor with pIC50 of 8.37 and 8.46 in HOS and PBL assays, respectively.

A potent, selective and orally bioavailable GPR119 agonist with EC50 of 4 nM, with good selectivity versus a battery of receptors, ion channels and enzymes; causes greater reductions in cumulative food intake and higher fed plasma GLP-1 and peptide tyrosine tyrosine levels and decreased plasma insulin and glucose-dependent insulinotropic polypeptide levels, when combined with metformin, in diet-induced obese mice.

A potent, relatively selective Nek2 inhibitor with IC50 of 82.74 nM in cell-free assays; inhibits only 3 kinases (YSK4, FLT3-ITDD835V and FLT3-ITDF691L) against 97 kinases with >65% inhibition at 15 nM; blocks NEK2-EZH2 complex formation and inhibits tumor cell proliferation; efficiently attenuates GBM growth in mouse model and exhibits a synergistic effect with radiotherapy.

A potent, ATP-competitive and relative selective Nek2 inhibitor with IC50 of 0.67 uM; displays >10-fold selectivity over CDK2.

A potent and selective TAF1(2) bromodomain inhibitor.

A novel STAT3 inhibitor (IC50=18.7 nM; Kd=10 nM) that strongly inhibits STAT3 and STAT5 phosphorylation without upstream kinase inhibition; induces significant growth inhibition in various hematopoietic malignant cells, particularly effective against multiple myeloma, Burkitt lymphoma and leukemia harboring BCR-ABL, FLT3/ITD and JAK2 V617F, oncokinases with their oncogenicities dependent on STAT3/5.

A novel small-molecule dual inhibitor of p53-MDM2/X interactions by potentially binding to p53, without effect on other MDM; causes growth inhibition, mediated by p53 stabilization and upregulation of p53 transcriptional targets involved in cell cycle arrest and apoptosis; shows a p53-dependent antitumor activity in human tumor xenograft mice models; a novel p53 activator.

A novel small molecule SH2 domain-targeting STAT3 inhibitor with IC50/Kd of 7.3/5 nM; does not bind to the S636A, V637A, and E638A SH2D mutants; effectively inhibits STAT3 phosphorylation (pTyr705 and pSer727) and cancer cell proliferation, impairs mitochondrial function; shows potent activity tumor xenografts in mice; orally bioactive.

A novel potent, selective, brain-penetrating, orally active CXCR4 antagonist with Ki of 3 nM; inhibits tumor growth alone, increases the antitumor effects of bevacizumab and sunitinib in preclinical models of human glioblastoma; reduces the expression of Nestin in vivo, reduces tumor cell proliferation and accelerates cancer stem cell differentiation in glioblastoma preclinical models.

A novel potent, nonpeptide CXCR4 antagonist with IC50 of 0.93 nM; induces increased and prolonged mobilization of murine HSPC compared to AMD3100.

A novel potent kynurenine-3-monooxygenase (KMO) inhibitor with IC50 of 4.5 nM.

A novel potent kynurenine-3-monooxygenase (KMO) inhibitor with IC50 of 2.3 nM and 0.7 nM for human KMO and Pf-KMO, respectively.

A novel potent IRE1α-selective kinase inhibitor that inhibits both the kinase and RNase activities of IRE1α with IC50 of 20 nM and 200 nM, respectively; binds to pIRE1α and inhibits XBP 1 splicing; only weakly inhibits Ron (IC50= 4.4 uM) and FGFR1 V561M (IC50=17 uM) in a panel of 284 kinases.

A highly potent, selective HCV NS5B polymerase inhibitor for treatment of HCV infection.

A drug-linker conjugate for antibody-drug conjugate by using the anti-mitotic agent, monomethyl auristatin E (MMAE), linked via the cleavable peptide SuO-Val-Cit-PAB.

A derivative of BAM-7 that acts as a nove potent, direct activator of Bax with EC50 of 700 nM; inhibits GBM cell proliferation, arrests the cell cycle, and induces apoptosis through the induction of mitochondrial membrane permeabilization; also blocks proliferation and self-renewal of GSCs and induces their apoptosis; sensitizes both GBM cells and GSCs to the alkylating agent Temozolomide.

A cell-permeable small molecule inhibitor of Fumarase (fumarate hydratase), an enzyme of the tricarboxylic acid cycle (TCA cycle); elicits a nutrient-dependent cytotoxicity in a number of cancer cell lines, and displays increased growth-inhibitory activity toward SW620 cell line grown in the absence of glucose (mean IC50=2.2 uM).

90 (CBR-490) is a potent and selective antiwolbachial activity compound (Anti-Wolbachia wMel In vitro HCI cell-based assay IC50=33 nM, IC90=283 nM).CBR490 demonstrates potent antiwolbachial activity was confirmed in L. sigmodontis, Brugia malayi, and Onchocerca ochengi in vivo preclinical models of filarial disease.CBR490 demonbstrated in vitro selectivity against Loa loa (a safety concern in endemic areas).

8-BOA is a selective and potent mechanism-based inactivator of breast cancer-associated CYP4Z1.8-BOA exhibited favourable inhibitory activity in vitro, thus meriting in vivo characterization.

3JC48-3 is a potent, cellularly active and stable c-Myc inhibitor, inhibits c-Myc-max dimerization with IC50 of 34 uM, 5 times more potent than 10074-G5, exhibits an approximate twofold selectivity for c-Myc-Max heterodimers over Max-Max homodimers.3JC48-3 inhibited the proliferation of c-Myc-over-expressing HL60 and Daudi cells with single-digit micromolar IC50 values by causing growth arrest at the G0 /G1 phase.3JC48-3 inhibited c-Myc-Max dimerization in cells validated by CoIP.3JC48-3 decreased prostate cancer cells' growth and viability in a dose-dependent fashion in vitro, upregulated PrKD1 expression and phosphorylation of known PrKD1 substrates: the threonine 120 (Thr-120) residue in beta-catenin and the serine 216 (Ser-216) in Cell Division Cycle 25 (CDC25C).3JC48-3 (1 g/kg, i.p.) decreased the rate of tumor growth in mice with patient-derived prostate cancer xenografts (PDX), without dose-limiting toxicity.

3-Deazauridine (DAU, NSC 126849) is a nucleoside analog that competitively inhibits cytidine triphosphate synthetase (CTP).3-Deazauridine inhibits the growth of L1210 leukemia cells when used at a concentration of 6 µM and dose-dependently reduces mortality in a mouse model of leukemia.3-Deazauridine selectively suppresses cell viability in a MYC-dependent manner in ARPE-19 cells.3-Deazauridine causes selective replication stress in MYC-overexpressing cells, which originates from MYC-driven rRNA synthesis.3-Deazauridine combined with ATR inhibitor BAY-1895344 induces synthetic lethality to MYC-overexpressing cells, and suppresses tumor growth in 3D assays and in vivo.

2S-alkyne is an irreversible and clickable inhibitor of Streptococcal pyrogenic exotoxin B (SpeB) with IC50 of 1.4 uM; 2S-alkyne showed irreversible enzyme inhibition in biochemical assays and labeled endogenous SpeB in cultured S. pyogenes supernatants. 2S-alkyne decreased S. pyogenes survival in the presence of human neutrophils and supports the role of SpeB-mediated proteolysis as a mechanism to limit complement-mediated host defense.

1-ECBC is a small molecule inhibiting C. albicans filamentation, 1-ABC targets DYRK1-family kinase Yak1, the sole DYRK-family member expressed in C. albicans.1-ECBC blocked C. albicans biofilm formation in several co-culture models and a rat catheter infection model.

13PCSK9i is a highly potent PCSK9-LDLR disruptor peptide with EC50 of 2 nM, SPR Kd of 6.1 nM and 21 nM for hPCSK9 and mPCSK9.13PCSK9i reduces plasma cholesterol levels and increases hepatic LDLR density in a dose-dependent manner.13PCSK9i functions by a unique, allosteric mechanism and is the smallest molecule identified to date with in vivo PCSK9-LDLR disruptor function.

(R,S′)-MNF is a bi-functional GPR55 inhibitor and biased β2 adrenergic agonist, inhibits proliferation of PDAC cell lines (IC50=0.11 uM, PANC-1 cells). (R,S′)-MNF is a biased β2-AR agonist that selectively signals through Gαs and does not recruit β-arrestin-2. (R,S′)-MNF attenuates pro-oncogenic signaling and cellular proliferation in PANC-1 cells. (R,S′)-MNF (1 uM) significantly decreased ERK phosphorylation stimulated by the GPR55 ligand O-1602, (R,S′)-MNF is an effective inhibitor of GPR55 internalization and signaling. (R,S′)-MNF (20-40 mg/Kg) reduces PANC-1 tumor growth in a mouse xenograft model.

(R)-STU104 is a potent, first-in-class TAK1-MKK3 porotein-protein interaction (PPI) inhibitor with SPR Kd of 71 nM for binding MKK3, disrupting the TAK1 phosphorylating MKK3.(R)-STU104 exhibited the potent inhibitory activity on TNF-α production on RAW264.7 cells with IC50 of 0.58 uM, suppressed the TAK1/MKK3/p38/MnK1/MK2/elF4E signal pathways.(R)-STU104 demonstrated remarkable dose-effect relationships on both acute and chronic mouse ulcerative colitis (UC) models.(R)-STU104 showed better anti-UC efficacy in vivo at 10 mg/kg/d than mesalazine at the dose of 50 mg/kg/d.

(R)-LMI (H2N-R-Leu-Met-Ile-COOH) is a tripeptide analogue of corticotropin-releasing factor (CRF) and CRF antagonist targeting the N-domain of CRF1 receptor; (R)-LMI inhibits CRF-stimulated cAMP accumulation with IC50 of 1.7 uM. (R)-LMI inhibits the production of interleukins by adipocytes and the proliferation rate of RAW 264.7 cells.