A-674563 is a potent, selective and orally available AKT inhibitor with Ki of 11 nM (Akt1); increases the efficacy of paclitaxel in a PC-3 xenograft model; enhances the transcription of several chondrocyte marker genes, including Col2a1, Acan and Col11a2, in mouse primary chondrocytes by inhibiting Sox9 degradation through the ubiquitin-proteasome pathway; also suppresses FLT3-ITD positive AML both in vitro and in vivo.

A-552 (A552) is a potent, small molecule antagonist of human IL-36γ, exhibits Ki of 31/54 nM in the human IL-36γ evoked CXCL1 release in human/mouse cellular assays.A-552 directly binds to human IL-36γ with IC50 of 67.6 nM measured by ITC, does not show affinity for either mouse IL-36γ, human IL-36α or IL-36β.A-552 attenuates human IL-36γ induced chemokine release in mouse plasma, and hIL-36γ induced inflammation in human 3D skin equivalents.A-552 is a novel first in class small molecule antagonist of the IL-36 signaling pathway that binds selective human IL-36γ and can dose-dependently inhibit IL-36γ induced production of proinflammatory cytokines from human and mouse cells.

A-1592668 (A 1592668) is a novel potent, CDK9-selective inhibitor with IC50 of 1.2 nM, >1000 fold selectivity over CDK1/2/7/8; A-1592668 also displays selectivity of ~12- and 240-fold over CDK4 and CDK6 respectively. A-1467729 inhibited phosphorylation of RNA pol-II (p-RNA pol-II; Ser2) with a potency of 26.7 nM at the cellular level, inhibited MCL-1 dependent hematologic tumor cell lines H929 (IC50=39 nM) and MV4-11 (IC50=42.4 nM) following 24 h of incubation.

A synthetic vitamin D3 analog that usually prescribed by a general practitioner or dermatologist for the treatment of psoriasis, chronic chapped lips and other severe dry skin conditions.

A small-molecule enhancer of autophagy through an mTOR-independent pathway; significantly reduces the number of eGFP-HDQ74-positive cells, and increases the transcript level of p62 in Atg5+/+ MEFs; significantly reduces levels of endogenous p62 and cell death in NPC1 hiPSC-derived neurons; enhances bacterial clearance and suppresses IL-1β Secretion in an autophagy-dependent manner; a valuable tool for studying the role of autophagy in the context of cellular homeostasis and disease.

A small molecule that inhibits tubulin polymerization.

A small molecule CD4-mimetic that binds gp120 and blocks CD4 binding, inhibits HIV-1 entry.

SAR340835 (SAR 340835, SAR296968 prodrug) is a potent, selective Na+/Ca2+ exchanger (NCX) inhibitor, a water-soluble prodrug of SAR296968.

SAR296968 (SAR 296968) is a potent, selective Na+/Ca2+ exchanger (NCX) inhibitor, potently inhibits hNCX1/2/3 with IC50 of 74/23/129 nM, respectively.SAR296968 showed the same range of inhibitory potency on NCX1 orthologs from dog, guinea pig, pig, rabbit, and rat (IC50=20-200 nM).SAR296968 inhibited both the forward and reverse mode of the NCX current in a concentration-dependent manner with similarly high potency in voltage-clamp studies in guinea pig cardiomyocytes.SAR296968 displays little to no effect against 5-HT2B, benzodiazepine peripheral receptor, norepinephrine uptake, dopamine uptake, AR and PR.SAR296968 exhibited antiarrhythmic properties in animal models of arrhythmias related to early or late afterdepolarizations, significantly increased left ventricular contractility in anesthetized pigs.

Neurounina-1 is a small molecule Na+/Ca2+ exchanger (NCX) activator, stimulates NCX1 and NCX2 activities with EC50 of 1.1-2.7 nM, does not affect NCX3 activity.Neurounina-1 (10 nM) reduced cell death of primary cortical neurons exposed to oxygen-glucose deprivation followed by reoxygenation, also reduced γ-aminobutyric acid (GABA) release, enhanced GABA(A) currents, and inhibited both glutamate release and N-methyl-d-aspartate receptors in vitro.Neurounina-1 effectively protects against stroke damage in vivo.

ARN22089 (ARN 22089) is a specific small molecule inhibitor of putative CDC42 family effector interaction, binds to CDC42 and has broad anti-cancer activity and inhibits MAPK and S6 signaling.ARN22089 could inhibit CDC42-PAK interactions with EC50 of 0.1 uM, and inhibit RHOJ/PAK interactions with approximate EC50 of 1-5 uM.ARN22089 has a single-digit micromolar IC50 activity against sensitive cell lines (WM3248, SKMel3, A375, and SW480), has IC50 of < 10 uM for 55/100 cell lines in a panel of 100 cancer cell lines with various different mutations, including several cell lines with neuroblastoma RAS (NRAS) mutations.ARN22089 inhibits MAPK and S6 phosphorylation and influences NFkB signaling in vitro.ARN22089 specifically inhibits tumor angiogenesis in 3D vascularized microtumors, shows drug-like properties and inhibits tumor growth in vivo.ARN22089 selectively binds and inhibits CDC42 effector interactions.ARN22089 binds better to the purified CDC42 compared with other known CDC42 inhibitors (ZCL278, ML141, R-ketoralac, and Casin).CDC42 family GTPases (RHOJ, RHOQ, CDC42) are linked to multiple human cancers and modulate cell-cycle progression, tumor cell migration/invasion, and tumor angiogenesis.

A potent, stable cyclohexapeptide somatostatin mimic that exhibits unique high-affinity binding to human somatostatin receptors (pKi=8.2/9.0/9.1/<7.0/9.9 for sst1/2/3/4/5, respectively); effectively inhibits GHRH-induced growth hormone release in primary cultures of rat pituitary cells with IC50 of 0.4 nM, also potently suppresses GH secretion in rats.

A potent, specific and mixed glycine transporter subtype 1 (GlyT1) inhibitor (pIC50=7.7) and GPR55 agonist (pEC50=6.5); shows no activity across a set of more than 200 validated molecular target assays from diverse classes, including kinases, proteases and other enzymes, GPCRs.

A potent, small molecule CXCR2 inhibitor with IC50 of 26 nM and 30 nM for mCXCR2 and hCXCR2, respectively; inhibits the growth and metastatic potential pancreatic ductal adenocarcinoma, enhances sensitivity to anti-PD1 immunotherapy in vivo; chemical analog of AZD 5069.

A potent, selective, small molecule motilin receptor agonist with pEC50 of 7.9 (hMTL-R); displays selectivity over closely related human ghrelin acceptor (pEC50< 6.0) and no liabilities at the hERG channel; possesses highly excellent pharmacokinetic profiles in both rat and dog.

A potent, selective, small molecule motilin receptor agonist with pEC50 of 7.9 (hMTL-R); displays selectivity over closely related human ghrelin acceptor (pEC50< 6.0) and no liabilities at the hERG channel; possesses highly excellent pharmacokinetic profiles in both rat and dog.

A potent, selective, orally active LXR agonist that recruits the steroid receptor coactivator 1 to human LXRα in a cell-free ligand-sensing assay with an EC50 of 125 nM; acts as a full agonist on hLXRα and hLXRβ in cell-based reporter gene assays with EC50 of 190 and 30 nM, respectively; increases expression of ABCA1 in the small intestine and peripheral macrophages in C57BL/6 mice at 10 mg/kg.

A potent, selective soluble guanylate cyclase (sGC) stimulator that increases sGC activity (cGMP formation) with EC50s of 27 and 25 nM for rat and human sGC, respectively; displays 23-fold selectivity for sGC over OATP1B1 and >197-fold selectivity over a panel of 38 proteins; increases P-VASP levels in rat aortic smooth muscle cells with EC50 of 12.7 nM; attenuates the development of cardiac hypertrophy in a blood pressure-independent fashion.

A potent, selective PDE4 inhibitor with pIC50 of 11.5, 11.3, 11.4, and 11.9 for PDE4B, A, C, and D, respectively; displays >380,000-fold selectivity over PDE1/23/5/6/7; inhibits TNFα production by lLPS-stimulated human peripheral blood monocytes with IC50 of 0.01 nM; inhibites LPS-induced pulmonary neutrophilia with ED50 of 1.1 ug/kg (aqueous suspension) and 2.9 ug/kg (dry powder formulation) in rats.

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.