And1 inhibitor CH3 is potent acidic nucleoplasmic DNA-binding protein 1 (And-1) inhibitor, reducess And‐1 expression level in IGROV1 cells with IC50 of 2.08 uM.CH3 induces acidic nucleoplasmic DNA‐binding protein 1 (And‐1) degradation via the E3 ubiquitin ligase CUL4B‐mediated proteasome degradation pathway.CH3 promotes the interaction between And‐1 and CUL4B by altering And‐1 conformation.CH3 exhibits the significant inhibition in a broad range of cancer cells in vitro and in vivo.CH3 (20 mg/kg and 40 mg/kg) reduced tumor growth of ovarian IGROV1 and breast MCF7 xenografts at both treated doses.CH3 also could overcome cisplatin resistance in ovarian cancer.And1 is an important factor for deoxyribonucleic acid (DNA) replication and repair, is overexpressed in many types of cancer but not in normal tissues.

AN12855 (AN-12855) is potent, cofactor-independent M. tuberculosis InhA inhibitor, binds to and inhibits InhA with IC50 of 0.03 uM, shows potent activity against whole-cell M. tuberculosis H37Rv with IC90 of 0.09 uM; AN12855 demonstrates potent activity against drug-susceptible and drug-resistant strains of M. tuberculosis, exhibits comparable efficacy to the frontline antitubercular drug isoniazid (INH) in both acute and chronic models of TB infection with a lower potential for resistance development and shows in vitro activity against conventional KatG-mediated INH-resistant M. tuberculosis.

An anthelmintic effective agent for pinworms that shows to be a potent inhibitor of Wnt signaling with EC50 of 10 nM; binds to all CK1 family members in vitro at low nanomolar concentrations and selectively potentiates CK1α kinase activity; inhibits Wnt signaling downstream of β-catenin, and promotes Pygopus degradation; also is a potent inhibitor of HH signaling by reducing the stability of the Gli family of transcription factors.

AMY-101 (Cp40) is a peptidic inhibitor of the central complement component C3 for the management of patients with ARDS caused by SARS-CoV-2 infection.AMY-101 is a novel complement C3-targeted therapeutic based on the 3 rd-generation compstatin analog Cp40.

AMXI-5001 Hcl (AMXI 5001) is a novel, highly potent, orally active dual PARP1/2 (IC50 5/0.05 nM) and microtubule polymerization inhibitor, inhibits intracellular PAR formation with IC50 of 7 nM.AMXI-5001 binds to the catalytic domain of human PARP1 and is a weak tankyrase inhibitor (800-fold lower than IC50 towards either PARP1 or PARP2 enzymes).AMXI-5001 inhibited tubulin polymerization in a dose-dependent manner.AMXI-5001 exhibited selective antitumor cytotoxicity across a wide variety of human cancer cells with much lower IC50s than existing clinical PARP1/2 inhibitors.AMXI-5001 is highly active in both BRCA mutated and wild type cancers.AMXI-5001 elicited a remarkable In vivo preclinical anti-tumor activity in a BRCA mutated TNBC model induced complete regression of established tumors, including exceedingly large tumors, demonstrated superior anti-tumor effects compared to either single agent (PARP or microtubule) inhibitor or combination with both agents.

Amphihevir is a potent, selective HCV NS4B inhibitor with EC50 of 0.34 and 1.97 nM against the GT1a (H77) and GT1b replicon in luciferase assays.Amphihevir shows weaker acitivity against GT2a (JFH-1) (EC50=186 nM).Amphihevir shows EC50 3.13 nM and 18.16 nM with 100% human serum against GT1a and GT1b replicons using HCV-1b replicon cells test.Amphihevir reduced replicon RNA by nearly 6,300-fold (3.8 log10) at a concentration 25-fold greater than the EC90 (300 nM).Amphihevir was found to be inactive against other viruses, human kinases, and GPCRs, which implies its good selectivity.Amphihevir has good oral bioavailability and appropriate T1/2 in rats and dogs, showed good safety profiles in rats and dogs.Amphihevir is the first reported NS4B inhibitor that has advanced to clinical trials.

Aminoxyrone is a novel peptidometic C-terminal HSP90 inhibitor by targeting HSP90 dimerization via the C-terminal domain (CTD) with Kd of 27.4 uM; destabilizes BCR-ABL1 without inducing HSR in vitro and in vivo, additionally reduces pAKT-S473, pS6 expression and expression of client proteins associated with HSP90 chaperone activity, involving t-AKT, t-STAT5a, t-CRKL, cMYC, and BCL2; triggers the degradation of HSP90 client proteins without elevating the expression of HSPs (HSP70, HSP40 & HSP27); significantly inhibits cell growth and induces apoptosis of human leukemic stem cells (LSCs) with average EC50 of 20.94 uM, Aminoxyrone is effective in imatinib resistant CML and lacks heat shock response.

AMD3451 is a specific, dual CXCR5/CXCR4 antagonist with antiviral activity against a wide variety of HIV-1 and HIV-2 (IC50=1.2 to 26.5 uM) in vitro.AMD3451 has antiviral activity against a wide variety of R5, R5/X4, and X4 strains if HIV-1 and HIV-2 in various T-cell lines, CCR5- or CXCR4-transfected cells, PBMCs, and monocytes/macrophages.AMD3451 inhibited R5, R5/X4, and X4 HIV-1 primary clinical isolates in PBMCs (IC50, 1.8 to 7.3 uM), AMD3451 blocks R5 and X4 HIV-1 infection at the virus entry stage.AMD3451 dose-dependently inhibited the intracellular Ca2+ signaling induced by the CXCR4 ligand CXCL12 in T-lymphocytic cells and in CXCR4-transfected cells, as well as the Ca2+ flux induced by the CCR5 ligands CCL5, CCL3, and CCL4 in CCR5-transfected cells.AMD3451 did not interfere with chemokine-induced Ca2+ signaling through CCR1, CCR2, CCR3, CCR4, CCR6, CCR9, or CXCR3 and did not induce intracellular Ca2+ signaling by itself at 400 uM.AMD3451 inhibited CXCL12- and CCL3L1-induced endocytosis in CXCR4- and CCR5-transfected cells.AMD3451 does not inhibit the binding of CXCR4- or CCR5-specific MAbs.

AM9928 is a potent, covalent monoacylglycerol lipase (MAGL) inhibitor with IC50 of 8.9 nM (hMAGL).AM9928 covalently binds to and inactivates MAGL by carbamylation of the enzyme's catalytic Ser122 nucleophile.AM9928 inhibited adhesion and transmigration of breast cancer cells through human brain microvascular endothelial cells (HBMECs), inhibited TNBC's secretion of inflammatory cytokines such as IL-6 and IL-8, and the angiogenic factor VEGF-A.AM9928 inhibited in vivo changes in BBB permeability and decreased TNBC colonization in brain.MAGL inhibitor AM9928 is a novel treatment of TNBC tumor growth and TNBC-colonization in the brain.

AM6580 is a potent, covalent monoacylglycerol lipase (MAGL) inhibitor with IC50 of 3 nM (hMAGL).AM6580 covalently binds to and inactivates MAGL by carbamylation of the enzyme's catalytic Ser122 nucleophile.

AM237 is a selective TRPC5 channel activator that potently activated homomeric TRPC5:C5 channels (EC50=15–20 nM in Ca2+i assays).AM237 did not activate TRPC4:C4, TRPC4-C1, TRPC5-C1, TRPC1:C5, and TRPC1:C4 channels, or native TRPC1:C4 channels in A498 cells, but potently inhibited EA‐dependent activation of these channels with IC50 values ranging from 0.9 to 7 nM.AM237 (300 nM) did not activate or inhibit TRPC3, TRPC6, TRPV4, or TRPM2 channels.AM237 potentiated TRPC5:C5 channels activation by sphingosine‐1‐phosphate but suppressed activation evoked by (−)‐englerin A (EA).AM237 concentration‐dependently suppressed further activation of Ca2+ influx mediated by EA with IC50 of 13 nM, potentiated TRPC5:C5 activation by S1P.Pico145 is a competitive antagonist of AM237‐mediated TRPC5:C5 activation.

ALRN-6924 (ALRN6924) is a potent dual inhibitor of MDM2/MDMX.ALRN-6924 demonstrated potent anti-proliferative activity in a dose-dependent manner in two ER+ cell lines with WT TP53, MCF-7 and ZR-75-1, with IC50 values of 113 nM and 500 nM respectively.The combination of ALRN-6924 and chemotherapeutic agents synergistically inhibit cell proliferation in vitro, ALRN-6924 combined with paclitaxel reactivates p53 and induces cell cycle arrest and apoptosis in vitro.ALRN-6924 mutually enhances both paclitaxel and eribulin antitumor efficacy and inhibits tumor growth in vivo.

Alphastatin-C is a 14-amino acids peptide consisting of a C-terminal fragment of the α-chain of Fgn, is a potent inhibitor of bFGF induced endothelial cell (HUVEC-CS) activation in vitro.Alphastatin-C inhibits tumor angiogenesis and reduces melanoma tumor growth, inhibits the chorioallantoic membrane (CAM) angiogenesis in chick model.Alphastatin-C efficiently reduces tumor number and volume in a melanoma mice model, due to the impairment of tumor neovascularization in treated mice.Alphastatin-C is an efficient new antiangiogenic FGF-associated agent in vitro, and inhibitor of embryonic and tumor vascularization in vivo, also is an arteriogenic agent

ALKBH5 inhibitor 6 is a small molecule inhibitor of RNA 6-N-methyladenosine (m6A) demethylase ALKBH5, inhibits ALKBH5 RNA m6A demethylation activity with IC50 of 1.79 uM.

ALKBH5 inhibitor 3 is a small molecule inhibitor of RNA 6-N-methyladenosine (m6A) demethylase ALKBH5, inhibits ALKBH5 RNA m6A demethylation activity with IC50 of 0.84 uM.

ALK2 R206H inhibitor 23 is a potent and selective inhibitor of Activin Receptor-Like Kinase-2 (ALK2/ACVR1) with IC50 of 8 nM for mutant ALK2 R206H.ALK2 R206H inhibitor 23 displays >15-fold selectivity over ALK1/ALK3, and >100-fold over ALK5/ALK6.

ALESIA is a specific sphingosine-1-phosphate receptor 3 (S1PR3)-G12-biased agonist and selectively induces G12 signal.ALESIA promotes nitric oxide production and oxidative stress.ALESIA selectively induces apoptosis in cancer cells because of low glucose levels.Intraperitoneal administration of ALESIA improved the survival of mice with peritoneally disseminated rhabdomyosarcoma.ALESIA (Anticancer Ligand Enhancing Starvation-induced Apoptosis) is a new anticancer compound for glucose starvation therapy.

ALDH inhibitor KS100 (KS100) is a novel, potent, multi-isoform ALDH inhibitor with IC50 of 207/1410/240 nM for ALDH1A1/ALDH2/ALDH3A1, respectively; KS100 was mitigated by development of a nanoliposomal formulation, called NanoKS100. NanoKS100 was 5-fold more selective for killing melanoma cells compared with normal human fibroblasts. Inhibition by KS100 significantly reduced total cellular ALDH activity to increase reactive oxygen species generation, lipid peroxidation, and accumulation of toxic aldehydes leading to apoptosis and autophagy.

AL906 (AL 906) is a novel potent, selective EGFR inhibitor with IC50 of 12 nM (EGFR phosphorylation).AL906 blocked EGF-induced EGFR phosphorylation at doses as low as 1 uM in EGF-stimulated OV90 and DU145 cells.AL906 growth inhibitory activity was superior to that of the clinical drug gefitinib.AL906 selectively inhibited the growth of the NIH3T3-EGFR and HER2 transfectants in isogenic NIH3T3 transfected cell panel.

AH237 (AH-237) is a potent and selective inhibitor for PRMT4 and PRMT5 with IC50 of 2.8 and 0.42 nM, respectively.AH237 (AH-237) displayed over 50-fold selectivity against a panel of 41 MTases such as PRMTs, PKMTs, NTMT1/2, and DNA methyltransferases (DNMTs), Its potency was also confirmed for PRMT1 (IC50 = 5.9 uM) and PRMT7 (IC50 = 831 nM).

AGH-192 is a potent, selective, orally bioavailable 5-HT7 receptor agonist with Ki of 4 nM.AGH-192 displays excellent water solubility, high selectivity over related CNS targets, high metabolic stability, oral bioavailability and low cytotoxicity.AGH-192 could crosses blood-brain barrier to a high extent.AGH-192 alleviates the symptoms of neuropathic pain in a mouse model.

ACHN-975 (ACHN975) is a potent bacterial LpxC inhibitor with IC50 of 0.68 nM (P. aeruginosa LpxC); ACHN-975 is potent against the P. aeruginosa isolates with MIC50 of 0.06 ug/mL and MIC90 of 0.25 ug/mL. ACHN-975 demonstrated in a neutropenic mouse thigh model with P. aeruginosa ATCC 27853.

ACC2 inhibitor 2e is a highly potent and selective acetyl-CoA carboxylase 2 (ACC2) inhibitor with IC50 of 1.9 nM and 1950 nM for ACC2 and ACC1, respectively.ACC2 inhibitor 2e exhibited good PK profile and in vivo antidiabetic efficacy in C57BL/6 mice.

ACAi-028 is a small molecule inhibiting HIV-1 replication (EC50=0.55 uM) that targets a hydrophobic pocket in the N-terminal domain of capsid (CA-NTD).ACAi-028 binds directly and noncovalently to HIV-1 capsid monomer.ACAi-028 inhibits the early stage of the HIV-1 life cycle and does not affect the late stage, also prevents multiple-round HIV-1 infection using HIV-1 strains (HIV-1NL4-3 and HIV-1LAI), except for HIV-2 strain (HIV-2ROD).ACAi-028 inhibits the replication of various types of HIV-1 strains (HIV-1104pre and HIV-1MDR/B) in PBMCs and HIV-1ATVR5μM in MT-4 cells, with negligible cytotoxicity.

AB-506 is a small-molecule inhibitor targeting HBV core protein, inhibits viral replication in vitro (IC50=77 nM).AB-506 binds to HBV core protein, accelerates capsid assembly and inhibits HBV pgRNA encapsidation.AB-506 blocks cccDNA establishment in HBV-infected HepG2-hNTCP-C4 cells and primary human hepatocytes, leading to inhibition of viral RNA, HBsAg, and HBeAg production (EC50=0.64-1.52 uM).AB-506 demonstrated activity across HBV genotypes A-H and maintains antiviral activity against nucleostide analog-resistant variants in vitro.AB-506 showed an 8 to 20-fold increase in EC50 values against L30F, L37Q, and I105T substitutions.AB-506 exhibits good oral bioavailability, systemic exposure, and higher liver to plasma ratios in rodents.

AB-452 (AB452) is a potent, small molecule inhibitor of noncanonical poly(A) polymerases PAPD5 and PAPD7 (PAPD5/7), inhibits PAPD5/7 enzymatic activities, reduces HBsAg in vitro (EC50=1.4/6.8 nM).AB-452 demonstrated specific antiviral activity for HBV, was inactive against a panel of 10 different RNA and DNA viruses with EC50 values of >30 uM.AB-452 reduced HBsAg, HBeAg, and HBV DNA production with EC50 of 0.28-6.8 nM, without cytotoxicity.AB-452 interferes with multiple steps of HBV life cycle by reducing HBV RNA.AB-452 demonstrated antiviral activity in AAV-HBV-transduced mouse model.AB-452 promotes HBV RNA degradation through inhibiting PAPD5 and PAPD7 enzymatic activities and blockage of guanosine incorporation into viral RNA poly(A) tails..

AA6216 (AA 6216) is novel potent, selective PDE4 inhibitor with IC50 of 0.63 nM.AA6216 showed stronger inhibitory effects against PDE4 than other PDE family members. AA6216 potently inhibits cytokine production (TNF-α,IL-12p40, IL-4, and IL-13, IC50s=2.2-7.9 nM) by PBMCs stimulated with PHA.AA6216 inhibited the production of TGF-β1 by a human monocytic cell line THP-1, AA6216 dose-dependently reduced the production of TNF-α by alveolar macrophages from patients with IPF.AA6216 demonstrated anti-fibrotic potency on mouse model of bleomycin-induced lung fibrosis.

A-9758 (A9758) is a selective, small molecule inverse agonist of retinoid-related orphan receptor gamma t (hRORγt IC50=38 nM).A-9758 also inhibits mouse RORγ transactivation with similar activity (20 nM) and is equally active on dog and rat RORγ (25 and 64 nM, repectively).A-9758 inhibits TCR-mediated IL-17A secretion with an IC50 of 100 and 38 nM in human CD4+ T cells and in vitro differentiated mouse Th17 cells, respectively.A-9758 exhibits robust potency against IL-17A release both in vitro and in vivo, significantly attenuates IL-23 driven psoriasiform dermatitis.A-9758 exhibits efficacy in an ex vivo human whole blood assay, is efficacious in human IL-17 related diseases.

A-908292 is a highly potent and selective acetyl-CoA carboxylase 2 (ACC2) inhibitor with IC50 of 38 nM (hACC2), no activity against ACC1 (IC50>30 uM).

A-745 (A745) is a selective and potent HPK1 chemical probe (inhibitor) of HPK1.A-745 demonstrates an excellent cellular selectivity binding profile within pharmacologically relevant concentrations in unbiased cellular kinase-binding assays.A-745 exhibited in vitro immune cell activation phenotype reminiscent of Hpk1-deficient and Hpk1-kinase-dead T cells, including augmented proliferation and cytokine production.A-745 is a selective and potent small molecule HPK1 inhibitors with the pharmacological properties for immunotherapy.