TMC647055 Choline Hydroxide Salt is a novel and potent non-nucleoside inhibitor of the HCV NS5B polymerase which potentially for the treatment of HCV infection. It has nanomolar cellular potency (EC(50) of 82 nM) with minimal associated cell toxicity (CC(

SI-2 is an inhibitor (SMI) of steroid receptor coactivator-3 (SRC-3 or AIB1). SI-2 can selectively reduce the transcriptional activities and the protein concentrations of SRC-3 in cells, and selectively induce breast cancer cell death with IC50 values in the low nanomolar range (3-20 nM), but not affect normal cell viability.

OSMI-4 is a low nanomolar O-GlcNAc transferase (OGT) inhibitor (EC50 of 3 μM in cells), which can be used to study OGT inhibition in different human cell lines.

LT052, a highly active and selective BET BD1 inhibitor with an IC50 of 87.7 nM, demonstrates nanomolar BRD4 BD1 potency and significant selectivity, being 138-fold more selective for BRD4 BD1 over BRD4 BD2 (IC50 =12.130 μM). Its anti-inflammatory properties make it a potential candidate for acute gout arthritis research [1].

BI-2852 is a KRAS inhibitor for the switch I/II pocket (SI/II-pocket) with nanomolar affinity. BI-2852 is leading to inhibition of downstream signaling and an antiproliferative effect in KRAS mutant cells.

Alpidem (Ananxyl) is an anxiolytic drug from the imidazopyridine family. Alpidem does not produce sedative effects at normal doses, and is instead used specifically for the treatment of anxiety. Alpidem has nanomolar binding affinity for both the central benzodiaze

CP-456773 (MCC950 (CP-456773) and CRID3) is an effective and specific cytokine release inhibitor and NLRP3 inflammasome inhibitor. CP-456773 inhibits IL-1β secretion and caspase 1 processing. MCC950 blocked canonical and noncanonical NLRP3 activation at nanomolar concentrations. MCC950 specifically inhibited activation of NLRP3 but not the AIM2, NLRC4 or NLRP1 inflammasomes. MCC950 reduced IL-1β production in vivo and attenuated the severity of experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis.

Charybdotoxin-Lq2 (ChTX-Lq2) is a potent inhibitor of calcium-activated potassium efflux, exhibiting a dissociation constant (Kd) of 43 nanomolar (nM) [1].

3-Iodothyronamine is derived from the deiodination and decarboxylation of endogenous thyroxine. It activates the G protein-coupled receptor known as trace amine-associated receptor 1 at nanomolar concentrations whereupon it rapidly influences thyroid hormone actions including body temperature, heart rate, and cardiac output. It has also been reported to function in controlling lipid and glucose utilization, hormonal secretion, and neuronal function, and has been considered for use in chemically-induced hibernation for medical purposes.

Potent Nav1.7 blocker (IC50 = 2.5 nM). Also inhibits Nav1.1, Nav1.2, Nav1.3 and Nav1.6 in the nanomolar range. Exhibits no effects on Cav channels or nAChR at 5 μM. Demonstrates analgesic activity in vivo; antagonizes effects of scorpion-venom toxin OD1 a

BRD9 Degrader-1 functions as a BRD9 degrader, demonstrating micromolar binding affinity towards BRD9 and nanomolar affinity for the ternary complex involving BRD9 and VCB [1].

ARCC-4 is an enzalutamide-based von Hippel-Lindau (VHL)-recruiting AR PROTAC and outperforms enzalutamide and it is a low-nanomolar androgen receptor (AR) degrader based on PROTAC, with a DC50 of 5 nM. ARCC-4 effectively degrades clinically relevant AR mutants associated with antiandrogen therapy[1].

FSCPX is a potent and selective irreversible antagonist of the A1 adenosine receptor (A1AR), exhibiting low nanomolar binding potency. Additionally, FSCPX can effectively decrease the interstitial adenosine level in the guinea pig atrium, thereby modifying the effect of NBTI, a nucleoside transport inhibitor.

1,4-Anthraquinone is an anticancer drug that blocks nucleoside transport, inhibits macromolecule synthesis, induces DNA fragmentation, and decreases the growth and viability of L1210 leukemic cells in the same nanomolar range as daunorubicin in vitro.1,4-

PF-07059013, an orally active and potent noncovalent modulator of sickled hemoglobin (HbS), specifically binds to Hb with nanomolar affinity and demonstrates substantial partitioning into red blood cells (RBCs), making it useful for sickle cell disease (SCD) research [1][2].

NF157 significantly decreases the expression of metalloproteinase (MMP)-3, MMP-13, which can be used in the treatment of osteoarthritis (OA). NF157 is a highly selective nanomolar P2Y11 antagonist (pKi: 7.35). The IC50s are 463 nM, 1811 µM, 170 µM for P2Y

PITCOIN4 is a Class II Alpha PI3K-C2α inhibitor with high selectivity, demonstrating nanomolar inhibition of PI3K-C2α and exhibiting over 100-fold selectivity against a broad kinase panel [1].

AuM1Gly, a topoisomerase I inhibitor, demonstrates efficacy in inhibiting the proliferation of MDA-MB-231 breast cancer cells, exhibiting IC50 values in the low nanomolar range [1].

DNA gyrase B-IN-2 (Compound E), a 2-aminobenzothiazole derivative, serves as a potent inhibitor of DNA gyrase B with substantial efficacy against ESKAPE pathogens. The compound exhibits potent nanomolar-range inhibition (IC 50 < 10 nM) and a broad-spectrum antibacterial effect, with minimum inhibitory concentrations below 0.03 μg/mL for most Gram-positive species and between 4–16 μg/mL for Gram-negative species including E. coli, Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. DNA gyrase B-IN-2 is applicable in infection research [1].

GCPII-IN-1 is a potent inhibitor scaffold targeting glutamate carboxypeptidase II (GCPII), also known as prostate-specific membrane antigen (PSMA). It exhibits a high affinity for GCPII, with a binding affinity (K i ) of 44.3 nanomolar (nM).

Chetomin (BRN0077366) is an inhibitor of HIF-1 by weaken transcription of HIF-1, disrupting the binding of HIF-1α and HIF-2α to p300 at low nanomolar concentrations.

Cisplatin-resistant cells-IN-1 (Compound 8) exhibits high cytotoxicity against Cisplatin-resistant cells and effectively diminishes metabolic activity at low nanomolar concentrations, with an IC50 ranging from 0.14 to 1.79 μM in various resistant cell lines, including A549/A549-R, K562/K562-R, and MCF-7/MCF-7TamR [1].

Brevetoxin B is a polyketide neurotoxin produced by Karenia species and other dinoflagellates. It binds to site 5 on the alpha subunit of voltage-gated sodium channels (IC50 = 15 nM) on neurons at the neuromuscular junction, causing the channel to open irreversibly at potentials more negative than normal, discharging action potentials repetitively. Brevetoxin B is ichthyotoxic at nanomolar concentrations and is responsible for an illness described as neurotoxic shellfish poisoning.

ARN19689 is an effective inhibitor of human NAAA, demonstrating high potency in the low nanomolar range (IC 50 = 0.042 μM). The compound acts through a non-covalent mechanism, highlighting its ability to interact with the enzyme for inhibition.

Argifin is a sub-nanomolar chitinase inhibitor produced by soil microorganisms (IC50: 0.025 μM, 6.4 μM, 1.1 μM and 4.5 μM for SmChiA (Serratia marcescens chitinaese A), SmChiB, Aspergillus fumigatus chitinase B1 and human chitotriosidase).

GNE-987 is a highly active chimeric BET degrader. GNE-987 binds equipotently to the BD1 and BD2 bromodomains of BRD4 with low nanomolar affinities (IC50: 4.7 and 4.4 nM, respectively). GNE-987 exhibits picomolar cell BRD4 degradation activity (DC50: 0.03

ICA-121431 (2,2-Diphenyl-N-[4-(thiazol-2-ylsulfamoyl) is a nanomolar potent small molecule Nav1.7 channel inhibitor with IC50 of 19 nM for rat Nav1.7, with little or no activity against human Nav1.5 or Nav1.7 channels.

BBDDL2059 is a selective covalent inhibitor targeting EZH2, exhibiting an IC50 of 1.5 nM against the EZH2-Y641F mutant. It demonstrates potency in inhibiting lymphoma cell proliferation at nanomolar concentrations, proving its utility in anticancer research [1].

Compound 17b, a TLR7 agonist also known as TLR7 agonist 14, exhibits high potency with an EC50 of 18 nM. It effectively activates mouse macrophages and human peripheral blood mononuclear cells (hPBMCs) at low-nanomolar concentrations [1].

CEP-14083 is a potent ALK inhibitor that has shown activity in an NPM/ALK–carrying T-cell lymphoma in vitro study. Presumably, this compound binds to the hinge region of the kinase in an ATP-competitive manner. CEP-14083 displays a potent activity against ALK in enzymatic assays (IC50 = 11 nmol/L). Further, CEP-14083 is also able to inhibit the insulin receptor at a concentration within a nanomolar range. In a preclinical assay, CEP-14083 showed that, via NPM/ALK TK inhibition, it could control the expression of molecules that determine T-cell identity and signaling in lymphoma cells. CEP-14083 has shown preclinical activity in both cell lines and animal models harboring ALK alteration.

PW0464, a nanomolar potent complete G protein biased ligand, is a noncatechol D1R agonist, with an EC50 of 5.8 nM (Gs-cAMP)[1]. PW0464 (compound 24) is found to elicit complete G protein bias, showing no activity for D1R-mediated β-arrestin recruitment[1].PW0464 (compound 24), the non-catechol agonist, forms bonds with S1985.42 and S2025.46 via its fluorine atom[2]. [1]. Pingyuan Wang, et al. Synthesis and Pharmacological Evaluation of Noncatechol G Protein Biased and Unbiased Dopamine D1 Receptor Agonists. ACS Med Chem Lett[2]. David R Sibley, et al. Novel Cryo-EM structures of the D1 dopamine receptor unlock its therapeutic potential. Signal Transduct Target Ther. 2021 May 22;6(1):205.

Downregulate phosphorylation of STAT3, increase the expression of cleaved caspase-3, inhibit cell cycle progression and promote apoptosis in breast and pancreatic cancer cells with low micromolar to nanomolar IC50 values. Furthermore, HJC-0123 significantly suppressed estrogen receptor (ER)-negative breast cancer MDA-MB-231 xenograft tumor growth in vivo (p.o.), indicating its great potential as an efficacious and orally bioavailable drug candidate for human cancer therapy.

Potent BRD9 degrader. Selectively binds BRD9 and elicits near complete degradation of BRD9 at nanomolar concentrations. Inhibits growth of synovial sarcoma cells in vitro and tumor progression in a synovial sarcoma xenograft mouse model.

AEG40730 is a potent and selective IAP antagonist and a BIR-binding tetrapeptide. AEG40730 binds to cIAP1 and cIAP2, facilitates their autoubiquitination and proteosomal degradation, and causes a dramatic reduction in RIP1 ubiquitination. Treatment with nanomolar concentrations of AEG40730 resulted in the loss of both XIAP and c-IAP1 proteins, albeit with different kinetics.

BAY-298 is an orally active and selective luteinizing hormone receptor (LH-R) antagonist with IC 50 s of 96 nM, 23 nM and 78 nM for hLH (human LH) and rLH (rat LH) and cLH (cynomolgus monkey LH), respectively. BAY-298 is the first nanomolar hLH-R antagonist reducing sex hormone levels in vivo[1].

Rhizopodin is a potent natural macrolide antibiotic that effectively affects the actin cytoskeleton at nanomolar concentrations.

Compounds 17o (IC50: 14.0 nM, NCI-H460) and 17p (IC50: 2.9 nM, NCI-H460) with furan moieties showed potent cytotoxic effects at the nanomolar level against various human cancer cell lines.

TDI-10229 is a potent and orally available inhibitor of soluble adenylyl cyclase (sAC, ADCY10). TDI-10229 displays nanomolar inhibition of sAC in both biochemical and cellular assays (IC50= 195 nM). TDI-10229 exhibits mouse pharmacokinetic properties sufficient to warrant its use as an in vivo tool compound.

Anticancer Agent 110 exhibits potent in vitro anti-leukemia activity, demonstrating high cytotoxicity against K-562 lineage chronic myelogenous leukemia cells at nanomolar concentrations. It induces DNA damage and subsequently triggers apoptosis [1].

PB2, a tris(2-carboxyethyl)phosphine (TCEP) analogue, enhances the survival of retinal ganglion cells (RGCs) following axotomy in vitro. Even at nanomolar and picomolar concentrations, PB2 demonstrates pronounced efficacy in promoting RGC survival. Notably, PB2 exhibits superior permeability compared to TCEP. Serving as a potent reducing agent, PB2 provides robust neuroprotection for RGCs[1].

BTZ043 is a DprE1 inhibitor with nanomolar bactericidal activity against Mycobacterium tuberculosis in vitro.

TLR7 agonist 15 (compound 16b) is a potent activator of mouse macrophages and hPBMCs, demonstrating an EC50 of 18 nM. It induces robust responses at low-nanomolar concentrations [1].

AXL-IN-15 (cpd391) is a potent inhibitor of Axl, exhibiting both a dissociation constant (K i) and a half-maximal inhibitory concentration (IC50) of less than 1 nanomolar (nM). It is applicable for cancer research [1].

S-72 acts as a microtubule polymerization inhibitor, effective in cell-free assays at concentrations of 1, 3, and 10 µM. At nanomolar levels (IC50s = 15.64 and 26.32 nM, respectively), it diminishes the viability of both MCF-7 and paclitaxel-resistant MCF-7/T breast cancer cells. Moreover, at 50 nM, S-72 impedes migration, invasion, and wound healing in these cell lines. Additionally, at 100 nM, it arrests the cell cycle at the G2/M phase and induces apoptosis in MCF-7/T cells, while also inhibiting stimulator of interferon genes (STING) activation. In vivo, S-72 dosage at 15 mg/kg per day curtails tumor growth in mouse xenograft models of paclitaxel-resistant breast cancer, specifically MCF-7/T and MX-1/T.

TfR-T12 TFA, a transferrin receptor (TfR)-binding peptide capable of crossing the blood-brain barrier (BBB), exhibits nanomolar (nM) binding affinity [1] [2].

IRC-083927 HCl is novel and potent microtubule inhibitor with potential anticancer activity. IRC-083927 inhibits the tubulin polymerization by a binding to the colchicine site. IRC-083927 inhibits in vitro cell growth of human cancer cell lines in the low nanomolar range. More interesting, it remains highly active against cell lines resistant to microtubule-interacting agents (taxanes, Vinca alkaloids, or epothilones). Chronic oral treatment with IRC-083927 (5 mg/kg) inhibits the growth of two human tumor xenografts in nude mice (C33-A, human cervical cancer and MDA-MB-231, human hormone-independent breast cancer). Together, the antitumor effects induced by IRC-083927 on tumor models resistant to tubulin agents support further investigations to fully evaluate its potential for the treatment of advanced cancers, particularly those resistant to current clinically available drugs.

JNJ-46281222 is an metabotropic glutamate (mGlu) 2-selective, highly potent PAM (positive allosteric modulator). It has nanomolar affinity (Kd = 1.7 nM) and a high modulatory potency (pEC50 = 7.71).

ST1936 oxalate is a selective, nanomolar affinity agonist of 5-HT6 receptor(Ki values of 13 nM, 168 nM and 245 nM for human 5-HT6, 5-HT7 and 5-HT2B receptors, respectively).

LFS-829 is a a small-molecule antagonist of exportin-1. LFS-829 showed low-range nanomolar activities. Oral administration of LFS-829 can significantly reverse the pathological features of colitis model mice. LFS-829 can attenuate dual NF-κB signaling and the Nrf2 cytoprotection pathway via targeting exportin-1 in colitis mice. Moreover, LFS-829 has a very low risk of cardiotoxicity and acute toxicity. LFS-829 holds great promise for the treatment of colitis and may warrant translation for use in clinical trials.

BIM-46050 is a potent and specific inhibitor of human farnesyltransferase. BIM-46050 is free acidic form of BIM-46068. The IC50 values for in vitro inhibition of human brain FTase indicate that BIM-46050 and the ester form BIM-46068 are potent inhibitors of farnesyltransferase. Their potencies are in the nanomolar range and compare favorably with the compounds B581, FTI-277 and L745,631. B581 is an analog of the tetrapeptide Cys-Val-Phe-Met obtained by replacement of the amino-terminal amide bonds inhibiting processing of farnesylated proteins specifically. FTI-277 is a methyl ester of FTI-276, reported as a preferential inhibitor of FTase over GGTase I (100-fold). L745,631 is a 2-substituted piperazine reported to be a highly selective inhibitor of FTase over GGTase (2,000-fold). The selectivity of BIM-46050 and BIM-46068 for FTase over GGTase is very similar for both compounds (3,000-fold).