BC-DXI-495 is a specific small molecule inhibitor of AIMP2-DX2-HSP70 interaction, specifically reduced the levels of DX2 (IC50=4.2 uM) but not AIMP2-F, and the viability of lung cancer cells (EC50=14 uM).BC-DXI-495 bound to DX2 with KD of 14 uM.BC-DXI-495 specifically reduced the levels of endogenous DX2 protein but not of AIMP2-F , affected the DX2 protein level, but not mRNA level.BC-DXI-495 inhibited DX2-dependent cell growth, significantly diminished tumor growth in a xenograft model of H460 cells, with little effect on body weigh.BC-DXI-495 significantly suppressed the growth and weight of tumors expressing DX2 WT, but not L80A mutant.

BAY-155 (BAY155) is a novel, potent and selective menin-MLL inhibitor with binding IC50 of 8 nM, 10-fold better compared to that of MI-503; BAY-155 demonstrated a significantly enhanced selectivity profile compared to MI-503 in a panel of assays covering numerous safety pharmacology-relevant targets including GPCRs, ion channels and transporters. BAY-155 shows anti-proliferative activity in a large cell line panel, exhibits specific therapeutic activityin AML/ALL models.

Bamocaftor (VX-659) is a next-generation CFTR corrector, restores F508del-CFTR protein function.

Azoffluxin (CMLD012336) is a bis-benzodioxolylindolinone that synergizes with fluconazole against C. auris through the inhibition of efflux pump Cdr1, thus increasing intracellular fluconazole levels.Azoffluxin increases intracellular accumulation of fluconazole (FLC) by inhibiting Cdr1-mediated efflux in C. auris.Azoffluxin potentiates intracellular acting compounds against C. auris, to a similar degree as deletion of CDR1.Azoffluxin is active against diverse C. auris strains, azoffluxin potentiated fluconazole in multiple isolates from three of the four major clades. The clade III isolates from South Africa were the exception.Azoffluxin enhances fluconazole (FLC) activity against azole-resistant C. albicans isolates.Azoffluxin not only enhanced fluconazole activity but also reduced fungal burden by ~1000-fold as a single agent in mice infected with drug-resistant C. auris.

Azo-EMD is a cell permeable, photoswitchable compound that inhibits mitotic kinesin Eg5 more potently in its light-induced cis form, used for optical control mitosis.Under UV light conditions, HeLa cells undergo mitotic arrest, as evidenced by the formation of a monopolar spindle.

AZD1332 is a potent, selective, ATP-competitive neurotrophic tyrosine kinase receptor (NRTK;TRK) inhibitor with IC50 of <10 nM; inhibits phosphorylation of TrkA/B/C in MCF10A cells overexpressing TrkA and NIH3T3 cells over expressing TrkA, TrkB, or TrkC with IC50 of <5 nM, inhibits a panel Baf3 survival driven by TrkA, TrkB, or TrkC with EC50 of 2 nM, AZD 1332 is orally available.

AZ7 (PI4KA inhibitor 7) is a potent, selective PI4KA inhibitor with pIC50 of 8.2, >100-fold selectivity over PI4Kβ, PI3Kα and PIP5Kγ.AZ7 inhibited the accumulation of IP1 (pIC50 6.3) caused a qualitative reduction in cellular PIP, PIP2 and PIP3 levels.PI4KA inhibitor 7 inhibited cell growth with pGI50 values of >5.0 in 91 of the cell lines in a panel of 183 cancer cell lines.

AZ3 (PI4KB inhibitor 3) is a seletive PI4KB inhibitor with pIC50 of 7.8, shows good lipid kinase selectivity (pIC50 5.1, 4.7 and 4.0 for PI4Kα, PI3Kα and PIP5Kγ respectively).

AXKO-0046 (AXKO0046) is the first highly selective, small molecule inhibitor of human lactate dehydrogenase B (LDHB), exhibits uncompetitive LDHB inhibition with EC50 of 42 nM.AXKO-0046 selectively inhibited LDHB activity in an uncompetitive manner with respect to NADH and pyruvate, no inhibitory activity against LDHA at 300 uM.AXKO-0046 did not bind in the catalytic site of the enzyme but significantly bound to LDHB in the novel allosteric site of the tetramer.AXKO-0046 is a promising chemical probe to elucidate the role of LDHB-associated pathways in cancer metabolism.

Autotaxin-IN-13 ( ATX-i) is a highly potent, selective Autotaxin inhibitor with IC50 of 6 nM.Autotaxin showed sufficient oral bioavailability and low plasma clearance in vivo as well as a suitable half-life to allow for bid or food admix dosing.

Autoquin is a novel autophagy inhibitor (IC50=0.56 uM) by indirect modulation of the activity of the lysosomal enzymes acid sphingomyelinase and acid ceramidase; Autoquin showed a dose‐dependent inhibition of EGFP‐LC3 puncta after 3 hours upon autophagy induction by amino acid starvation in the primary screening assay. Autoquin is a lysosomotropic compound that acts as a functional inhibitor of acid sphingomyelinase, increases lysosomal mass and sequesters Fe2+ to the lysosomes in MCF7 cells, causing an increase in lysosomal reactive oxygen species.

Autophazole is a novel autophagy inhibitor, promotes cancer cell death via caspase activation.Autophazole was internalized into lysosomes of cells where it induced lysosomal membrane permeabilization (LMP), promoted LMP-mediated apoptosis.LMP induced by Autophazole caused release of cathepsins from lysosomes into the cytosol. Cathepsins in the cytosol cleaved Bid to generate tBid, which subsequently activated Bax to induce mitochondrial outer membrane permeabilization (MOMP).Autophazole is a new chemical probe in efforts aimed at gaining a better understanding of the autophagic process.

Autophagy inducer D61 is a small molecule autophagy inducer with antibacterial activity, induces LC3II and promotes aggregation of LC3II near Salmonella.D61 (25 uM) reduced the bacterial load (GFP signal in RAW 264.7 macrophages) by 20-fold, with IC50 of 1.3 μM in the SAFIRE assay.D61 antibacterial activity depends on the VPS34 complex and on ATG5.D61 also reduced Salmonella load in the spleens and livers of infected mice.D61 antibacterial activity in macrophages is synergistic with the antibiotic chloramphenicol but that this synergy is largely independent of the known autophagy-stimulating activity of chloramphenicol.Salmonella enterica is a natural bacterial pathogen of humans and animals that causes systemic infection or gastroenteritis.

Atg4B inhibitor 21f is a potent competitive inhibitor for Atg4B with Ki of 3.1 uM.Atg4B inhibitor 21f enhanced the anticancer activity of anti-CRPC drugs via autophagy inhibition.

AstraZeneca CCR4 antagonist is a potent, selective CCR4 antagonist, inhibits CCR4 ligand macrophage-derived chemokine (MDC/CCL22) in CCR4+CD4+ T cells.

ASR490 (ASR 490) is a small molecule that binds to NRR of Notch1, specifically inhibits Notch1-mediated survival of colorectal cancer cells (IC50=0.6-1.2 uM); ASR490 overcomes Notch1 overexpression and inhibits the growth of HCT/Notch1 transfectants, reduces Notch1-mediated tumor burden in xenografts.

ASP9822 is a novel potent selective CDK7 inhibitor with IC50 of 4.3 nM, with anti-cancer activity.

ASP2205 (ASP2205 fumarate) is a potent, selective 5-HT2C receptor agonist with EC50 of 0.85/2.5 nM for human/rat 5-HT2C in the intracellular Ca2+ mobilization assays, respectively.ASP2205 showed partial agonistic action on human 5-HT2A receptor with EC50 of 96 nM, no agonistic action against 5-HT2B.ASP2205 (0.1-1 mg/kg, i.d.) significantly elevated the leak point pressure (LPP) in anesthetized rats in a dose-dependent manner.ASP2205 is a more potent and selective 5-HT2C receptor agonist than lorcaserin.

ASK120067 is a novel third-generation inhibitor of EGFR T790M (L858R/T790M IC50=0.3 nM, T790M IC50=0.5 nM), with selectivity over EGFR WT (IC50=6 nM).ASK120067 potently inhibited the EGFR L858R/T790M and EGFR T790M resistant mutants, with IC50 of 0.3 nM and 0.5 nM, respectively, as well as the EGFR exon19del sensitizing mutant (IC50= 0.5 nM).ASK120067 also displayed a favorable selectivity profile against a panel of 258 kinases.ASK120067 selectively inhibits the growth of EGFR-mutant cell lines and induces apoptosis, with IC50 values of 12 nM, 6 nM and 2 nM against NCI-H1975, PC-9, and HCC827 cells, respectively.ASK120067 dose-dependently inhibited EGF-induced EGFR L858R/T790M phosphorylation and consequent activation of the downstream molecules AKT and ERK in NCI-H1975 cells, with similar or even more effective potency than osimertinib.ASK120067 (5, 10 mg/kg once daily) demonstrated profound and selective antitumor efficacy in EGFR-mutant xenograft models in vivo.

ASIC1a inhibitor 5b is a highly selective and potent ASIC1a inhibitor, inhibits proton-evoked ASIC1a currents with an apparent IC50 of 27 nM at pH 6.7.ASIC1a inhibitor 5b can potently and selectively inhibit acid-induced activation of ASIC1a-containing channels, including both ASIC1a homotrimers and ASIC1a-ASIC2 heterotrimers, in a pH-dependent manner.ASIC1a inhibitor 5b binds to the acidic pocket of ASIC1a, exhibits a dramatic leftward shift under pH 6.7 activation of ASIC1a as compared to pH 6.0.ASIC1a inhibitor 5b protected neurons from ASIC1a-dependent cell death and is blood-brain barrier permeable.ASIC1a inhibitor 5b (5 mg/kg) attenuated neurological impairment and alleviated infarct volume in mouse MCAO model of ischemic stroke.

AS2690168 is a novel orally available, selective RANKL signal transduction inhibitor, reduces TRAP staining of sRANKL-stimulated RAW264 cells with IC50 of 0.28 uM, suppresses RANKL-induced osteoclastogenesis.AS2690168 suppressed soluble RANKL (sRANKL)-induced NFATc1 mRNA expression in RAW264 cells with 37.1% and 98.9% inhibiyion at 0.3 and 3.0 uM, respectively.AS2690168 also suppressed calcium release from parathyroid hormone-stimulated mouse calvaria with an IC50 value of 0.46 uM.AS2690168 (3 mg/kg, p.o.) completely suppressed the decrease in femoral bone mineral content in an sRANKL-induced osteopenic mice model, also significantly suppressed the decrease in femoral bone mineral density and increase in serum tartrate-resistant acid phosphatase-5b levels in ovariectomized rats at doses of 0.3, 1 and 3 mg/kg.AS260168 suppressed the increase in urine deoxypyridinoline in a rat prednisolone-induced osteoporosis model at 10 mg/kg.

AS2690168 is a novel orally available, selective RANKL signal transduction inhibitor, reduces TRAP staining of sRANKL-stimulated RAW264 cells with IC50 of 0.28 uM, suppresses RANKL-induced osteoclastogenesis.AS2690168 suppressed soluble RANKL (sRANKL)-induced NFATc1 mRNA expression in RAW264 cells with 37.1% and 98.9% inhibiyion at 0.3 and 3.0 uM, respectively.AS2690168 also suppressed calcium release from parathyroid hormone-stimulated mouse calvaria with an IC50 value of 0.46 uM.AS2690168 (3 mg/kg, p.o.) completely suppressed the decrease in femoral bone mineral content in an sRANKL-induced osteopenic mice model, also significantly suppressed the decrease in femoral bone mineral density and increase in serum tartrate-resistant acid phosphatase-5b levels in ovariectomized rats at doses of 0.3, 1 and 3 mg/kg.AS260168 suppressed the increase in urine deoxypyridinoline in a rat prednisolone-induced osteoporosis model at 10 mg/kg.

Artepillin C (CREB-CRTC2 inhibitor APC) is an inhibitor of CREB/CRTC2 interaction (IC50=24.5 uM), dissociates the CREB/CRTC2 complex, directly binds to CREB with Kd of 3.2 uM.CREB-CRTC2 inhibitor APC inhibits CRTC2 interacting with CREB-ZIP and reduces acetyltransferase activity of CBP by binding with CREB protein directly.Artepillin C attenuated gluconeogenesis in primary hepatocytes, reduced glucose output from primary hepatocytes induced by glucagon, remarkably decreased the mRNA accumulation of G6pc, Pck1, and Pgc-1α induced by glucagon in primary hepatocytes.|Artepillin C could ameliorate hyperlipidemia in obese mice.

ARN-75041 (ARN75041) is a potent, small molecule fusion inhibitor of arenavirus, inhibits pseudotyped entry of pGTOV and pCHAPV with EC50 of 1.7 and 15.3 nM, respectively. ARN-75041 demonstrated sub-nanomolar against native replicative LASV (LASV EC90<0.3 nM) and JUNV (EC90=6.2 nM).ARN-75041 also potently inhibits mutant T434I pTCRV variant with EC50 of 29 nM.ARN-75041 dramatically improved survival outcome and potently inhibited TCRV replication in serum and various tissues at doses of 10 and 35 mg/kg, provided highly significant post-exposure protection in mice against TCRV infection.

ARN-75039 (ARN75039) is a potent, small molecule fusion inhibitor of arenavirus, inhibits pseudotyped entry of pGTOV and pCHAPV with EC50 of 0.13 and 4.3 nM, respectively.ARN-75039 demonstrated sub-nanomolar EC50 activity against pTCRV that further translated to native wild-and NWAs, including LASV, JUNV and MACV, in pseudotyped virus assays and against native replicative LASV and JUNV.ARN-75039 also potently inhibits mutant T434I pTCRV variant with EC50 of 29 nM.ARN-75039 dramatically improved survival outcome and potently inhibited TCRV replication in serum and various tissues at doses of 10 and 35 mg/kg, provided highly significant post-exposure protection in mice against TCRV infection.

ARN24092 (ARN-4092) is a potent, selective inhibitor of Na+-K+-Cl- importer NKCC1, shows significant dose-dependent inhibition of NKCC1 in the Ca2+ influx assay (51.9% at 100 uM).ARN24092 did not show any significant inhibition of NKCC2 in the Cl-influx assay nor inhibition of KCC2 in the thallium (Tl) influx assay.ARN24092 (i.p, 0.6 mg/kg, daily) restored the short-term working memory of Ts65Dn mice in the T-maze test, completely restored associative memory in Ts65Dn mice in the contextual fear-conditioning (CFC) test, without side effects showed in health of the mice.

ARN23765 (ARN 23765) is a highly potent, pharmacological corrector of the mutant CFTR chloride channel with EC50 of 38 pM in cellular assays; ARN23765 is more than 5000-fold lower compared to presently available corrector drugs. ARN23765 also showed high efficacy, synergy with other types of correctors, and compatibility with chronic VX-770 potentiator.

AP-202 (AP202) is a highly potent and selective α4β2 nAChR antagonist with binding Ki of 18 nM, 57-fold selectivity over α3β4 receptor.AP-202 is agonist activity, also dispalys 40-fold, 10-fold and 90-fold selectivity over α4β4, α3β2, α3β4α5 receptors, does not activate α7 nAChR or block acetylcholine induced changes in membrane potential.AP-202 showed significant activity in blocking nicotine priming-induced as well as cue-induced reinstatement of nicotine seeking in vivo.

Antimicrobial peptide BING (IRIILRAQGALKI) is a thermostable 13-residue peptide that targets bacterial envelope stress response by suppressing cpxR expression in Gram-negative bacteria.BING downregulates efflux pump components and synergises the effect of antibiotics, and suppresses the development of antibiotic resistance.BING downregulated the expression of efflux pump components mexB, mexY and oprM in P. aeruginosa and significantly synergised the toxicity of antibiotics towards these bacteria.

anle145c is a small molecule inhibitor of amyloid aggregation and formation, inhibits human islet amyloid polypeptide (hIAPP)-induced death of INS-1E cells.anle145c has a special mode of action in which anle145c-stabilized oligomers act as a thermodynamic sink for the preferred aggregation state of hIAPP and anle145c.anle145c prevents hIAPP fibril formation in solution, and converts preformed hIAPP fibrils into non-toxic oligomers.anle145c is a promising candidate to inhibit protein aggregation in case of T2DM.