pocket

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.

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

Debio 0932 (CUDC-305) is a heat shock protein 90 (Hsp90) inhibitor that targets the n-terminal atp-binding pocket to promote apoptosis, and has the advantage of being orally available and able to cross the blood-brain barrier (BBB) for the treatment of cancers such as non-small-cell lung cancer (NSCLC) and neuroblastoma.

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.

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.

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.

MB710 is an amino benzothiazole derivative that binds tightly to the Y220C pocket and stabilizes p53-Y220C in vitro. It exhibits anticancer activity and can be used in cancer research.

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].

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).

Nutlin-3 is an MDM2 antagonist that inhibits MDM2-p53 interaction (Ki=90 nM) and activates p53. Nutlin-3 binds preferentially to the p53-binding pocket of MDM2, leading to stabilization of p53 and activation of the p53 pathway. Nutlin-3 has antitumor activity.

COH29 (RNR Inhibitor COH29) is an orally available, aromatically substituted thiazole and human ribonucleotide reductase (RNR) inhibitor with potential antineoplastic activity. COH29 binds to the ligand-binding pocket of the RNR M2 subunit (hRRM2) near the C-terminal tail, decreasing the pool of deoxyribonucleotide triphosphates needed for DNA synthesis, leading to cell cycle arrest and growth inhibition. It may also inhibit the nuclear enzyme poly (ADP-ribose) polymerase (PARP) 1, preventing DNA repair, causing accumulation of DNA breaks, and inducing apoptosis.

ICCB-19 hydrochloride (ICCB-19 HCl) is an inhibitor of TRADD (TNFRSF1A Associated Via Death Domain). It binds to a pocket on the N-terminal TRAF2-binding domain of TRADD (TRADD-N), which interacts with the C-terminal domain (TRADD-C) and TRAF2 to modulate the ubiquitination of RIPK1 and beclin 1.

AMG410 is a non-covalent, bimodal GDP (OFF) and GTP (ON)-binding pan-KRAS inhibitor with Kd (GDP) = 1 nM and Kd (GTP) = 22 nM, which enables circulation-independent blockade of KRAS. AMG410 is more than 100-fold selective for KRAS than HRAS and NRAS2, binds on the same variegated pocket as KRAS G12C inhibitors, and has high potency in KRAS G12D, G12V, G12C, G13D and other mutants, IC 50 = 1-4 nM. AMG140 regresses tumors and reduces phosphorylated ERK levels in colorectal, pancreatic and lung models of KRAS mutations.

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.

OD36 is a selective and potent RIPK2 inhibitor with an IC50 of 5.3 nM.OD36 inhibits ALK2 signaling and osteogenic differentiation (KD: 37 nM), and binds efficiently to the ALK2 kinase ATP pocket.

K-Ras-PDEδ-IN-1 is a potent inhibitor of competitive K-Ras-PDEδ that binds to the farnesyl binding pocket of PDEδ (Kd of 8 nM).

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

Bozitinib (PLB-1001) (PLB-1001) is a highly selective inhibitor of the c-MET kinase with blood-brain barrier permeability. Bozitinib binds to the conventional ATP-binding pocket of the tyrosine kinase superfamily.

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.

Vapendavir diphosphate (BTA798 diphosphate) is a rhinoceros enterovirus inhibitor that targets the hydrophobic pocket in the viral capsid and is a capsid-binding agent with antiviral activity that prevents viral entry into the cell. Vapendavir diphosphate inhibits EV71 replication.

ARP-100 (MMP-2 Inhibitor III) is a potent and selective matrix metalloproteinase MMP-2 inhibitor (IC50=12 nM). ARP-100 interacts with the S1' pocket of MMP-2 and exhibits anti-invasive properties in an in vitro invasion Matrigel model. ARP-100 has low inhibitory activity against MMP-1 (>50 μM), MMP-3 (4.5 μM), MMP-7 (>50 μM) and MMP-9 (0.2 μM)[1][2].

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.

INDY is an ATP-competitive inhibitor of Dyrk1A and Dyrk1B with IC50s of 0.24 μM and 0.23 μM and a Ki of 0.18 μM for Dyrk1A ATP pocket, respectively.

MLT-747 is an effective and allosteric inhibitor of MALT1. It binds MALT1 in the allosteric Trp580 pocket (IC50: 14 nM).