SB 202190 (FHPI) is a p38 MAPK inhibitor that inhibits p38α and p38β2 (IC50=50/100 nM) selectively and cell-permeably. SB 202190 has antitumor activity and also induces the differentiation of human embryonic stem cells into cardiomyocytes.

FM04 is an orally active and highly potent inhibitor of P-glycoprotein (P-gp) with an EC50 value of 83 nM. FM04 can interact with Q1193 and I1115 in human P-gp nucleotide binding domain 2 (NBD2). Thereby disrupting the R262-Q1081-Q1118 interaction pocket and uncoupling the ICL2-NBD2 interaction, thereby inhibiting P-gp. FM04 can be used in the treatment of cancer and tumors.

Trifluoromethyl-tubercidin (TFMT) inhibits host MTr1 and suppresses virus replication. TFMT inhibits MTr1 through interaction at its S-adenosyl-l-methionine binding pocket to restrict influenza virus replication. TFMT was effective in inhibiting viral replication in mice, displayed little toxicity.

DCAI is an inhibitor of nucleotide exchange and nucleotide release acting by binding to the pocket adjacent to the Ras-SOS interface.

MB710, an aminobenzothiazole derivative, stabilizes the oncogenic p53 mutation Y220C by binding tightly to the Y220C pocket, enhancing the stability of p53-Y220C with a dissociation constant (Kd) of 4.1 μM. This compound exhibits anticancer activity in cell lines harboring the p53-Y220C mutation [1].

BA-53038B is an HBV core protein allosteric modulator (CpAM), binding to the HAP pocket and modulating HBV capsid assembly in a distinct manner (EC50: 3.32 μM).

JAK3-IN-11 (Compound 12) exhibits potent, noncytotoxic, irreversible, orally active JAK3 inhibitory activity (IC50 = 1.7 nM) with an excellent selectivity profile (>588-fold compared to other JAK isoforms), covalently binds to the ATP-binding pocket in JAK3. JAK3-IN-11 strongly inhibits JAK3-dependent signaling and T-cell proliferation which is a promising tool for studying autoimmune diseases [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.

VPC-13566 is a BF3-specific small molecule, which effectively inhibited the androgen receptor transcriptional activity and displaced the BAG1L peptide from the BF3 pocket. VPC-13566 inhibits the growth of various prostate cancer cell lines and reduces the growth of AR-dependent prostate cancer xenograft tumors in mice.

COH29 (RNR Inhibitor COH29) is an orally available, aromatically substituted thiazole and inhibitor of the human ribonucleotide reductase (RNR), with potential antineoplastic activity. Upon oral administration, the RNR inhibitor COH29 binds to the ligand-binding pocket of the RNR M2 subunit (hRRM2) near the C-terminal tail. Inhibition of RNR activity decreases the pool of deoxyribonucleotide triphosphates available for DNA synthesis. The resulting decrease in DNA synthesis causes cell cycle arrest and growth inhibition. In addition, this agent may inhibit the nuclear enzyme poly (ADP-ribose) polymerase (PARP) 1, which prevents the repair of damaged DNA and causes both the accumulation of single and double strand DNA breaks and the induction of apoptosis.

CXCL12 ligand 1 is the first ligand of the sY12-binding pocket on chemokine CXCL12 .

Necrostatin-34 (2-{[3-cyano-4-(4-methylphenyl)-6-oxo-1,4) is a RIPK1 kinase inhibitor, stabilizing RIPK1 kinase in an inactive conformation by occupying a distinct binding pocket in the kinase domain.

SWTX-143, a novel covalent inhibitor, specifically and irreversibly binds to the palmitoylation pocket of all four TEAD isoforms, inhibiting the transcriptional activity of the YAP/TAZ-TEAD complex and demonstrating antitumor activity [1].

Aplithianines A effectively inhibits J-PKAcα with an IC50 value of 1 μM and displays higher potency against wild-type PKA, achieving an IC50 of 84 nM by competitively interacting with the ATP pocket [1].

This peptide, generated from the BH3 domain of Bak (Flu-BakBH3), has been shown to have high-affinity binding to a surface pocket of the Bcl-XL protein that is required for its death antagonist function.

JNJ-67569762 is a selective BACE1 inhibitor targeting the S3 pocket ( IC 50 = 2.7 nM).

PHD-1-IN-1 is a potent inhibitor of hypoxia-inducible factor prolylhydroxylase domain-1 (PHD-1) enzyme(IC50 = 0.034 μM).

FTO-IN-10 (compound 7), a potent inhibitor of the human demethylase FTO (fat mass and obesity-associated protein), exhibits an IC50 of 4.5 μM. It interacts with the binding pocket of FTO's structural domain II via hydrophobic and hydrogen bonding interactions, and promotes DNA damage and autophagic cell death in A549 cells [1].

FAK-IN-11 (Compound 4l), a FAK inhibitor, specifically targets the ATP binding pocket of FAK to prevent its phosphorylation. It exhibits cytotoxic effects on MDA-MB-231 cells, achieving an IC50 value of 13.73 μM, and induces non-apoptotic cell death in these cells [1].

GW841819X is an analogue of (+)-JQ1 and a novel inhibitor of BET bromodomains. GW841819X was a single enantiomer but of undefined chirality at the 4-position of the benzodiazepine ring3. GW841819X and JQ1 were recently discovered that bind to the acetyl-lysine binding pocket of BET bromodomains with Kd ranges from 50 to 370 nM [1]. GW841819X bounded to both the individual BD1 and BD2 domains with affinities of 46 and 52.5 nM, respectively. GW841819X-Brd3 interaction was estimated to be around 70 nM4. GW841819X displayed activity in vivo against NUT-midline carcinoma, multiple myeloma, mixed-lineage leukemia, and acute myeloid leukemia1. It also potent induced the ApoA1 reporter gene with an EC50 of 440 nM. It had very little effect on LDL-R luciferase activity at the concentrations at which it induces ApoA1 expression, suggesting that the effect is indeed specific3. GW841819X competed directly with GATA1 site for BD1 binding and also specifically blocked the interaction between Brd3 and acetylated GATA14. Recent findings reported that GW841819X are chose as an interest compound to further develop into potential drugs against diseases including cancer, HIV infection and heart disease2.

Resveratrol-3-O-sulfate is a metabolite of resveratrol . In U-937 cells stimulated with LPS, resveratrol-3-O-sulfate (1 μM) decreases the expression of IL-1α, IL-1β, and IL-6 by 61.2, 76.6, and 42.2%, respectively, and decreases the release of TNF-α and IL-6 to similar levels as resveratrol. It has antioxidant activity in a Trolox assay, dose-dependently decreases growth of Caco-2 colorectal adenocarcinoma cells when used at concentrations ranging from 10 to 100 μM, and induces apoptosis at concentrations of 25 and 50 μM. Resveratrol-3-O-sulfate also displaces rosiglitazone from the outer mitochondrial protein mitoNEET (IC50 = 3.36 μM for the human protein), indicating that it binds to the thiazolidine-2,4-dione (TZD) binding pocket.

R-10015 is a highly potent and selective LIMK inhibitor that blocks LIMK by binding to the ATP-binding pocket. It inhibits human LIMK1 with an IC50 value of 38 nM. It also exerts broad-spectrum antiviral effects and may be used in HIV infection research.

MeOIstPyrd is an anti-skin cancer agent that inhibits cell proliferation, migration, and spheroid formation through activation of the mitochondrial intrinsic apoptotic pathway. It induces DNA damage, activates p53, prolongs its half-life, and stabilizes p53 via ser15 phosphorylation. Additionally, MeOIstPyrd interfaces with MDM2 within the p53 sub-pocket, preventing the p53-MDM2 interaction [1].

RS-104966 is an inhibitor of collagenase that acts by inducing the conformational change in the side-chains of the S1 pocket of MMP-1.

C188 is a cell-permeable naphthol compound and a STAT3 inhibitor. C188 inhibits IL-6-stimulated STAT3 Tyr705 phosphorylation and nuclear translocation in HepG2 cells by targeting STAT3 SH2 domain peptide-binding pocket, while exhibiting little effect agai

PS77 is a Pkh inhibitor directed to the PIF-pocket with increased selectivity for C. albicans Pkh2.

GP29 is a Type II kinase inhibitor of the IRE1α endoribonuclease that acts by targeting the ATP-binding pocket of IRE1α.

NP603 is a cell-permeable inhibitor of FGFR1, PDGFRβ, and VEGFR2 that binds to the ATP pocket. It also is a very weak EGFR inhibitor.

TKIM is a TWIK-related potassium channel 1 (TREK-1) inhibitor, binding to the pocket of the intermediate (IM) state of TREK-1.

CL-82198, a selective MMP-13 inhibitor, serves as a pharmacological intervention to halt the progression of osteoarthritis (OA). Its mechanism of action involves binding to the S1’ pocket of MMP-13, ensuring its selectivity and preventing inhibition of other MMPs.

Apostatin-1 (Apt-1) is a novel TRADD inhibitor. Apostatin-1 can bind to a pocket on the N-terminal TRAF2 binding domain of TRADD.

DCLX069 is a potent and selective PRMT1 inhibitor. DCLX069 occupies the SAM binding pocket to exert the inhibitory effect. DCLX069 effectively blocks cell proliferation in breast cancer, liver cancer and acute myeloid leukemia cell lines.

KRA-533, a potent KRAS agonist, directly targets the GTP/GDP binding pocket within the KRAS protein, inhibiting GTP cleavage. This inhibition leads to the buildup of constitutively active GTP-bound KRAS, which subsequently activates both apoptotic and autophagic cell death pathways specifically in cancer cells.

CM026 is a selective aldehyde dehydrogenase 1A1 inhibitor that acts by binding within the aldehyde binding pocket of ALDH1A1 in an uncompetitive partial mode of inhibition.

Antifungal agent 40 is an antifungal agent that extends into the narrow hydrophobic pocket II of C. alb. CYP51 and inhibits the activity of lanosterol 14α-demethylase (CYP51), which has an inhibitory effect on biofilm formation.

AP-22161 selectively binds the Src SH2 domain by targeting highly conserved phosphotyrosine binding to cysteine residues in the pocket. AP-22161 selectively inhibits Src SH2 binding and can be used to inhibit osteoclast absorption.

BI-207524 is a novel NS5B Thumb Pocket 1 Inhibitor with Improved Potency for the Potential Treatment of Chronic Hepatitis C Virus Infection.

UNC2541 is a potent and Mer tyrosine kinase (MerTK)-specific inhibitor. It also binds in the MerTK ATP pocket (IC50: 4.4 nM). UNC2541 inhibits phosphorylated MerTK (pMerTK; EC50, 510 nM).

BMS-309403 sodium is a potent, orally active, selective inhibitor of the adipocyte fatty acid binding protein (FABP4, aP2), demonstrating inhibitory constants (K i ) of <2, 250, and 350 nM for FABP4, FABP3, and FABP5, respectively. It operates by competitively binding to the fatty-acid-binding pocket of the protein, thereby impeding the attachment of endogenous fatty acids. This compound has been shown to enhance endothelial function both in apolipoprotein E-deficient mice and cultured human endothelial cells, underlining its potential therapeutic benefits [1] [2] [3].

PS423 is a substrate-selective protein kinase PDK1 inhibitor that acts by binding to the PIF-pocket allosteric docking site.

KRas/son of sevenless 1 (SOS1) interaction inhibitor. Binds within nucleotide binding pocket of KRas (Kd values are 106 - 176 nM for wild type KRas and various KRas mutants). Inhibits nucleotide binding to KRas in a concentration dependent manner. Display

IG-105 is a potent microtubule inhibitor with potential anticancer activity. IG-105 inhibits microtubule assembly by binding at colchicine pocket. IG-105 shows a potent anticancer activity in vitro and in vivo and has good safety in mice. IG-105 showed a potent activity against human leukemia and solid tumors in breast, liver, prostate, lung, skin, colon, and pancreas with IC(50) values between 0.012 and 0.298 mumol/L. It was also active in drug-resistant tumor cells and not a P-glycoprotein substrate. It inhibited microtubule assembly followed by M-phase arrest, Bcl-2 inactivation, and then apoptosis through caspase pathways.

L002, a potent, cell-permeable, reversible, and specific acetyltransferase p300 (KAT3B) inhibitor with an IC50 of 1.98 μM, directly binds the acetyl-CoA pocket and competitively inhibits the FATp300 catalytic domain. By blocking histone acetylation, p53 acetylation, and STAT3 activation, L002 shows potential in the treatment of hypertension‐induced cardiac hypertrophy and fibrogenesis.

Aliskiren(CGP 60536) is an orally effective renin inhibitor with IC50 of 1.5 nM. IC50 value: 1.5 nM [1] Target: renin in vitro: Aliskiren hemifumarate appears to bind to both the hydrophobic S1/S3-binding pocket and to a large, distinct subpocket that extends from the S3-binding site towards the hydrophobic core of renin. Oral bioavailability of Aliskiren hemifumarate is 2.4% in rats, 16% in marmosets and about 2.5% in humans [2]. in vivo: Aliskiren hemifumarate (< 10 mg/kg, oral) inhibits plasma renin activity and lowers blood pressure in sodium-depleted marmosets[3].Once-daily oral treatment with Aliskiren hemifumarate lowers blood pressure effectively, with a safety and tolerability profile, in patients with mild-to-moderate hypertension[4].

ARS-1323-alkyne is a switch-II pocket (S-IIP) inhibitor and a conformational specific chemical reporter of KRASG12C nucleotide state in living cells.

CBS1194 is a novel antiviral agent against influenza A virus (IAV), and is more specifically, a group 2 IAV fusion inhibitor. CBS1194 prevents membrane fusion of the virus through the inhibition of the conformational change of hemagglutinin (HA). CBS1194 causes steric hinderance that prevents the rearrangement of the HA that would normally be induced by low-pH, by fitting into the pocket by the fusion peptide.

OD36 hydrochloride (OD-36 hydrochloride) is a potent RIPK2 inhibitor with an IC50 of 5.3 nM.OD36 hydrochloride is a macrocyclic inhibitor that binds efficiently to the ATP pocket of the ALK2 kinase and effectively antagonizes mutant ALK2 signaling and osteogenic differentiation.OD36 hydrochloride targets ALK2. OD36 hydrochloride targets ALK2 with a KD of 37 nM.

PVZB1194, a biphenyl-type inhibitor of Kinesin spindle protein Eg5 (KIF11), exhibits anticancer potential by inducing cell cycle arrest and apoptosis through inhibiting Eg5 ATPase activity. It binds to the α4/α6 allosteric pocket and demonstrates ATP-competitive activity [1].

BH3I-2' is a cell-permeable BH3 mimetic. BH3I-2' induces apoptosis by specifically preventing BH3 domain-mediated interactions between pro-apoptotic and anti-apoptotic members of the Bcl-2 family, thereby blocking the interaction between Bcl-x and Bak BH3 by targeting the Bcl-x binding pocket.

Ivaltinostat (CG-200745) formic is an oral active panHDAC inhibitor with an isohydroxamic acid component that binds zinc at the bottom of the catalytic pocket. Ivaltinostat formic inhibited the deacetylation of histone H3 and tubulin. Ivaltinostat formic promotes p53 accumulation, induces p53-dependent trans activation, and enhances MDM2 and p21 (Waf1/Cip1) protein expression. Ivaltinostat formic increases the sensitivity of Gemcitabine resistant cells to Gemcitabine and 5-Fluorouracil (5-FU). Ivaltinostat formic induces apoptosis and has antitumor effect.