protein-rna interaction

TLR3-IN-1 (CU CPT 4a) is a selective TLR3 inhibitor (IC50: 3.44 μM in RAW 264.7 cells). It can inhibit TLR3/dsRNA complex-mediated downstream signaling pathways and inhibit the production of TNF-α and IL-1β in whole cells.

Quarfloxin (CX-3543) is a fluoroquinolone derivative with antineoplastic activity with IC50 values in the nanomolar range in neuroblastoma cells. Quarfloxin disrupts the interaction between the nucleolin protein and a G-quadruplex DNA structure in the ribosomal DNA template.

PT-129 is a PROTAC degrader targeting the NTF2 domain of G3BP1/2, capable of inhibiting and degrading stress granules in stressed cells, disrupting ATF4 trafficking, and suppressing fibroblast-mediated cancer cell proliferation.

FAZ-3780 (compound G3Ib) is an inhibitor that binds to the NTF2L domain of G3BP1/2, exhibiting a binding affinity to G3BP1 with a Kd of 0.54 μM. It specifically targets the protein-protein interaction domain of G3BP1/2 and inhibits the co-condensation of G3BP1, caprin 1, and RNA in vitro.

Fli-1-IN-1 (compound 21) fumarate is an FLI1-targeting agent that binds directly to and inhibits the interaction of the EWS-FLI1 protein. Since EWS-FLI1 interacts with RNA helicase A, Fli-1-IN-1 fumarate's inhibition of EWS-FLI1 suggests potential anticancer properties.

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.

I3IN-002 is a small molecule inhibitor targeting the RNA-binding protein IGF2BP3, with an IC50 value of approximately 2 μM in SEM cells. It disrupts the interaction with m6A-modified mRNA, destabilizing target genes (such as CDK6, MYC, and BCL2), thereby inhibiting the growth of leukemia cells, inducing cell cycle arrest, and promoting apoptosis. I3IN-002 shows potential for research in B-cell acute lymphoblastic leukemia.

Glycosyltransferase-IN-2 (Compound 20) is an inhibitor of glycosyltransferase with broad-spectrum antiviral activities against coronaviruses. It shows IC50 values of 11.3 μM for MHV, 5.5 μM for HCoV-NL63, and approximately 16.2 μM for SARS-CoV-2. This compound can interfere with coronavirus infectivity, alter viral protein glycosylation, inhibit interaction with the ACE2 receptor, and suppress secretion of cytotoxic viral particles (SC-VLP) and RNA replication. Glycosyltransferase-IN-2 is utilized in coronavirus infection research.

MX69 is the MDM2/XIAP inhibitor, blocking the MDM2 protein-XIAP RNA interaction, leading to MDM2 degradation.

AMP-PNP tetralithium（Adenylyl-imidodiphosphate tetralithium） is a non-hydrolyzable ATP analog that fully occupies ATP-binding sites without undergoing enzymatic hydrolysis, thereby providing stable and controlled experimental conditions for dissecting ATP-dependent biological processes. AMP-PNP is widely used to investigate enzyme activity, kinase regulation, DNA and RNA metabolism, ion channel function, and protein complex assembly in biochemical and structural biology studies.

CR-1-31-B, a synthetic rocaglate, acts as a highly potent inhibitor of eIF4A. By disrupting the interaction between eIF4A and RNA, it effectively obstructs the initiation phase of protein synthesis. Specifically, CR-1-31-B interferes with the association between Plasmodium falciparum eIF4A (PfeIF4A) and RNA. Additionally, CR-1-31-B induces apoptosis in neuroblastoma and gallbladder cancer cells [4].

Anticancer agent 73 is an anticancer agent which potently targets transactivation response(TAR) RNA-binding protein 2 (TRBP) and disrupts the TRBP-Dicer interaction. Anticancer agent 73 suppresses the growth and metastasis of HCC in vitro and in vivo by modulating expression profiles of miRNAome and proteome in HCC cells.

CDK-IN-9 (compound 24) is a potent inhibitor of CDK and acts on CDK2/E (IC50: 4 nM). It functions as a molecular gel that induces interaction between CDK12 and DDB1, and can dephosphorylate retinoblastoma protein and RNA polymerase II, thereby inducing apoptosis.

Azaphilone-9 (AZA-9) functions as an inhibitor of the HuR-ARE RNA interaction, with an inhibition constant (IC50) of 1.2 μM, by targeting the RNA-binding protein Hu antigen R (HuR). As HuR-RNA interactions play a critical role in stabilizing oncogenic mRNAs within tumors, Azaphilone-9 exhibits potential in inhibiting cancer cell growth and progression.

PINT-87aa, an 87-amino acid (aa) peptide encoded by the circular form of the long intergenic non-protein-coding RNA p53-induced transcript (LINC-PINT), directly interacts with the polymerase associated factor complex (PAF1c) to inhibit the transcriptional elongation of multiple oncogenes, effectively suppressing glioblastoma cell proliferation both in vitro and in vivo [1].

MYC-RIBOTAC, a ribonuclease-targeting chimera (RIBOTAC) specific to the MYC internal ribosome entry site (IRES), comprises an MYC mRNA-binding element tethered to a small molecule that recruits and activates RNase L1. This interaction promotes the degradation of MYC mRNA, subsequently reducing MYC protein levels and inducing apoptosis, thereby presenting potential applications in anticancer research [1].

TMV-IN-6 (Compound 4g) is a novel antiviral and fungicidal agent that obstructs tobacco mosaic virus (TMV) assembly by binding to the TMV coat protein (CP) and disrupting the interaction between TMV CP and RNA [1].

PTBP1 α3-helix derived peptide P1 TFA is a cell-permeable, rationally designed stapled peptide that inhibits RNA binding by the Polypyrimidine Tract-Binding Protein 1 (PTBP1). PTBP1 α3-helix derived peptide P1 TFA is used in RNA-binding protein interaction research systems to study inhibition of PTBP1–RNA complex formation and modulation of post-transcriptional gene regulation. PTBP1 α3-helix derived peptide P1 TFA is further applied in mechanistic molecular biology studies investigating spliceosome-associated regulatory pathways and RNA processing dynamics in cellular models.

LIN28-IN-1 (compound 5) is a selective inhibitor targeting the RNA-binding protein LIN28, binding specifically to its cold shock domain (CSD). This compound interrupts the LIN28-let-7 miRNA interaction with an IC50 of 5.4 μM, mitigating LIN28's adverse effects on epigenetic gene control. LIN28-IN-1 also exhibits significant anti-proliferative activity against LIN28-expressing JAR cancer cells, with an IC50 value of 6.4 μM [1].

CDK9-Cyclin T1 PPI-IN-1 (Compound B19) is a selective inhibitor of the CDK9-Cyclin T1 protein-protein interaction (PPI), suppressing cell proliferation in TNBC MDA-MB-231 cells with an IC50 of 0.044 μM and inducing apoptosis. This compound diminishes CDK9 transcriptional activity and downregulates phosphorylation of RNA Pol II CTD ser2. In vivo, CDK9-Cyclin T1 PPI-IN-1 effectively impedes tumor growth in a TNBC 4T1 mouse model [1].

Tat-CIRP, a peptide inhibitor, impedes the protein-protein interaction between myeloid differentiation 2 (MD-2), also known as lymphocyte antigen 96 (LY96), and cold-inducible RNA binding protein (CIRP) by binding to MD-2. This disrupts the MD-2 and CIRP interaction as confirmed in co-immunoprecipitation assays. Notably, in vivo studies reveal that Tat-CIRP, at dosages of 10 and 20 mg/kg, significantly reduces infarct volume in both a mouse model of middle cerebral artery occlusion (MCAO) and a rhesus monkey model of thrombosis-induced stroke. Additionally, it improves motor function, evidenced by decreased time to manipulate and withdraw food with the affected arm in the primate model.

Fli-1-IN-1 (compound 21) serves as a FLI1 inhibitor by binding directly to the EWS-FLI1 protein, disrupting its interaction with RNA helicase A. This inhibition holds potential anticancer properties [1].

TK-216 D4 is a deuterated isomer of TK-216. TK216 is an orally active E26 transcription factor (ETS) inhibitor. TK216 binds to the EWS-FLI1 fusion protein, blocking its protein-protein interaction with RNA helicase A (RHA/DHX9) and inhibiting ETS transcription factor-mediated oncogene transcription. TK216 is used in cancer research.

Fleephilone is a fungal metabolite isolated from Trichoderma harzianum. It acts as an HIV REV/RRE binding inhibitor, hindering the interaction between REV protein and RRE RNA with an IC50 of 7.6 μM.