protein–protein interaction (ppi)

ZW4864 (free base) is an orally active and selective β-catenin/B-Cell lymphoma 9 protein-protein interaction (β-catenin/BCL9 PPI) inhibitor, with a K_i value of 0.76 μM and an IC_50 value of 0.87 μM [1]. ZW4864 (free base) also demonstrates good pharmacokinetic properties.

BRCA1-IN-2 is a cell membrane-crossing BRCA1 protein-protein interaction (PPI) inhibitor with antitumor activity that acts by disrupting the interaction of BRCA1 (BRCT)2 with proteins.

Dri-c21045 showed concentration-dependent inhibition of NF- B activation and all CD40L induced by B cell proliferation. IC50 was 17.1 M and 4.5 M, respectively.Dri-c21045 is an effective selective inhibitor of CD40-CD40L synergistic stimulator protein-pro

IPR-803 is an effective inhibitor of the uPAR·uPA protein-protein interaction (PPI) with anti-tumor activity. IPR-803 binds directly to uPAR with a Ki of 0.2 μM.

S1g-10 is an Hsp70/Bim inhibitor that exhibits significant antitumor activity, particularly in chronic myeloid leukemia (CML) cells. It inhibits the protein-protein interaction between Hsp70 and Bim, blocking cancer cell survival signals and inducing apoptosis. S1g-10 is an optimized derivative of S1g-2, with a 10-fold increase in anticancer potency.

Keap1-Nrf2-IN-27 is an inhibitor of the Keap1-Nrf2 protein-protein interaction (PPI) with a KD2 value of 0.119 μM. It suppresses the expression of pro-inflammatory cytokines TNF-α and IL-6 in an LPS-induced RAW264.7 cell model.

Keap1-Nrf2-IN-18 (Compound 22) is an orally active inhibitor of the Keap1-Nrf2 protein-protein interaction (PPI), demonstrating favorable pharmacokinetic (PK) properties and enhanced in vivo efficacy in rats. In structure-activity relationship (SAR) studies, Keap1-Nrf2-IN-18 exhibits the strongest inhibitory activity (KD = 0.0029 μM).

Keap1-Nrf2-IN-19 (compound 33) is an orally active inhibitor of the Keap1-Nrf2 protein-protein interaction (PPI), with a Kd value of 0.0014 μM. Keap1-Nrf2-IN-19 exhibits less than 50% inhibition of hERG at 30 μM and CYPs at 10 μM.

LPPM-8 is a ligand for Med25 and acts as an inhibitor of Med25 protein-protein interactions (PPI). It engages with Med25 via the H2 surface of its activator-interaction domain, thereby stabilizing full-length proteins in the cellular proteome. LPPM-8 is an orthosteric inhibitor of H2-binding transcription activators (e.g., ATF6a). Med25 plays a role in the transcriptional regulation of RNA polymerase II-dependent genes and can form a transcription complex with ATF6α. LPPM-8 is valuable for studying the complex biology of Med25 and its Mediator complex.

WDR5-MYC-IN-2 is an inhibitor of the WDR5-MYC protein-protein interaction (PPI) with an IC50 of 0.59 μM. It is utilized in research on MYC-driven cancers and in the development of other potent WDR5-MYC PPI inhibitors.

Hsp90-Cdc37-IN-4 is a novel derivative of triptolide that inhibits the protein-protein interaction (PPI) between Hsp90 and Cdc37. It selectively inhibits casein kinase 2 (CK 2), reducing the phosphorylation of its substrate Cdc37 at the serine 13 site. Additionally, Hsp90-Cdc37-IN-4 induces cell cycle arrest in the G0/G1 phase and triggers apoptosis via the mitochondrial pathway. This compound exhibits significant anti-breast cancer activity.

CD-10 is an orally active inhibitor of the Keap1-Nrf2 protein-protein interaction (PPI) that can penetrate the blood-brain barrier. It binds to Keap1 with a KD value of 193 nM. CD-10 exerts significant antioxidant and anti-inflammatory effects by activating the Keap1-Nrf2 pathway, demonstrated by reduced levels of MDA, IL-4, and IL-10, and increased expression of HO-1 protein. In a chronic unpredictable mild stress (CUMS) mouse model, CD-10 effectively alleviates anxiety and depressive behaviors and restores serum neurotransmitter levels by promoting Nrf2 nuclear translocation. CD-10 is applicable for research in depression.

KI-TOX-A3 is a selective protein-protein interaction (PPI) inhibitor targeting the TOX protein, with an IC50 value of 0.51 μM for the TOX-KAT7 interaction. It promotes proteasomal degradation of TOX, restores KAT7-mediated H3K14 acetylation, reverses CD8+ T cell exhaustion, and inhibits proliferation of T-cell acute lymphoblastic leukemia (T-ALL) cells. KI-TOX-A3 holds potential for research in hematological malignancies, including T-ALL.

eIF4E/eIF4G PPI-IN-1 is an inhibitor that disrupts the interaction between eIF4E and eIF4G, exhibiting a dissociation constant (KD) of 20.2 μM for the eIF4E protein. It demonstrates antitumor effects through various mechanisms, including modulation of eIF4E activity via inhibition of the Ras/MAPK/eIF4E signaling pathway, influencing apoptosis and cell migration. Additionally, eIF4E/eIF4G PPI-IN-1 inhibits the growth of HepG2 xenografted tumors in nude mice and is relatively non-toxic to mice.

PEX5-PEX14 PPI-IN-3 (Compound 7) is an inhibitor of the PEX5-PEX14 protein-protein interaction, with an EC50 of 95 μM. It demonstrates an EC50 of 7.2 μM against Trypanosoma brucei and exhibits low cytotoxicity in HepG2 cells. PEX5-PEX14 PPI-IN-3 also possesses antiparasitic activity.

MDK-3298 is a reversible covalent inhibitor of Mcl-1, a target of protein-protein interaction (PPI).

ISIR-005 is a natural stabilizer of the 14-3-3/Gab2 protein-protein interaction (PPI) interface.

RAS inhibitor Abd-7 is a powerful compound (Kd=51 nM) that binds to RAS and inhibits the protein-protein interaction (PPI) between RAS and its effectors. By interacting with RAS within cells, RAS inhibitor Abd-7 hinders RAS-effector interactions and suppresses endogenous RAS-dependent signaling. Additionally, RAS inhibitor Abd-7 disrupts the PPI of different mutant KRAS proteins with PI3K, CRAF, RALGDS, as well as NRAS Q61H and HRAS G12V[1].

β-Catenin-IN-37 is a selective inhibitor of the protein-protein interaction between β-Catenin and T-cell factor (Tcf), known as β-catenin/Tcf PPI. It effectively inhibits canonical Wnt signaling and impedes the growth of colorectal cancer cells SW480 and HCT116, with IC50 values of 20 μM and 31 μM, respectively.

PCSK9-IN-2 is a newly developed small molecule that effectively inhibits the protein-protein interaction (PPI) between PCSK9 and LDLR. It has been found to have a potent inhibitory activity with an IC50 value of 7.57 μM.

ZW4864 is a selective inhibitor of the β-catenin/B-Cell Lymphoma 9 protein (β-catenin/BCL9 PPI) interaction, demonstrating oral activity. It inhibits β-catenin/BCL9 PPI with a K_i value of 0.76 μM and an IC_50 value of 0.87 μM.

M2I-1 a small Mad2 inhibitor-1. the first small molecule inhibitor targeting the binding of Mad2 to Cdc20, an essential proteinprotein interaction (PPI) within the SAC. It can disturbs conformational dynamics of Mad2 critical for complex formation with Cd

TAS1553 is a highly effective, orally bioavailable protein-protein interaction (PPI) inhibitor with an IC50 value of 0.0396 μM. It effectively hinders DNA replication and diminishes the intracellular dATP pool. Moreover, TAS1553 induces apoptosis, making it a valuable compound in cancer research [1].

(R)-STU104 is a novel TAK1-MKK3 protein-protein interaction (PPI) inhibitor that inhibits TNF-α and suppresses the TAK1/MKK3/p38/MnK1/MK2/elF4E signalling pathway by binding to MKK3 and disrupting TAK1 phosphorylation of MKK3. (R)-STU104 is a candidate compound for the treatment of ulcerative colitis.