Apoptose

RIPK1ligand-Linker Conjugate-1 is a Target Protein Ligand-Linker Conjugate that consists of a RIPK1 ligand and a PROTAC linker, designed to recruit E3 ligase. It is utilized in the synthesis of PROTACRIPK1Degrader-1.

TrxR1-IN-2 (Compound 6a) acts as a TrxR1 inhibitor that covalently bonds with the Cys475 and Sec498 sites of TrxR1. This interaction hampers TrxR1 activity, resulting in a redox homeostasis disruption and inducing apoptosis and ferroptosis.

AY-4 (Compound AY-4) is a potent PROTAC degrader targeting FTH1, with a dissociation constant (Kd) of 3.17 nM. It effectively increases intracellular ferrous (Fe2+) and ferric (Fe3+) ion levels. AY-4 is a potential anticancer candidate that regulates iron homeostasis through ferritin degradation, enhancing the efficacy of existing drugs. Additionally, AY-4 significantly reduces FTH1 levels in breast cancer cells.

Obestatin (human) is an endogenous ligand for G-protein eurythmic entity 39 formed by shearing of preproghrelin and can be used to study obesity.

PROTACROR1degrader-1 (Compound 11d) serves as a PROTAC degrader targeting the pseudokinase ROR1, with the capability of degrading ROR1 in NSCLC cells at a DC50 of 40-80 nM. It induces PARP cleavage and apoptosis in NCI-H23 cells. [Pink: ligand for target protein ROR1 ligand-1; Black: linker; Blue: ligand for VHL E3 ligase (S,R,S)-AHPC]

DSTYSLSSTLTLSK TFA detects infliximab, a chimeric IgG1 antibody targeting TNF-α.

AMPK-IN-6 (compound 13a) is a potent AMPK inhibitor with an IC50 value of 0.093 µM. It induces apoptosis and suppresses autophagy. Additionally, AMPK-IN-6 exhibits antiproliferative activity and holds potential for research into pulmonary arterial hypertension.

VEGFR-2-IN-61 (Compound 7b) is an inhibitor of VEGFR-2 with an IC50 of 2.83 µM. It effectively inhibits the proliferation of various cancer cells, including MCF-7 cells, with an IC50 of 2.12 µM. Additionally, VEGFR-2-IN-61 suppresses cell migration and induces oxidative stress and apoptosis in MCF-7 cells.

DP-15 acts as a degrader of GSPT1 and BRD4, with DC50 values of 5.25 nM and 0.48 nM, respectively. This compound exhibits antiproliferative activity in AML and NHL cells, showing IC50 values in the nanomolar range, induces G1 phase cell cycle arrest, and triggers apoptosis in MOLM13 cells. Additionally, DP-15 demonstrates anti-leukemic properties in the MOLM-13 xenograft mouse model. [Pink: ligand for target protein JQ-1 carboxylic acid; Black: linker; Blue: ligand for E3 ligaseCereblonThalidomide-5-OH]

CGP-74514,CDK1 inhibitor (IC50=25 nM). Induces G2/M arrest, apoptosis. Used in bladder cancer research.

PROTACPI3K/110β degrader-2 is a selective PI3K/p110β PROTAC degrader. It effectively degrades the 110β protein and inhibits the expression of P-glycoprotein. Additionally, it increases reactive oxygen species (ROS) levels. PROTACPI3K/110β degrader-2 exerts antitumor effects by activating the endoplasmic reticulum stress (ERS) mediated mitochondrial apoptosis pathway and inhibiting the AKT/Bcl-2 signaling pathway. This compound is applicable in cancer research.

YTHu78 is a KDM5B PROTAC-based degrader. It induces the degradation of KDM5B through the ubiquitin-proteasome system and triggers apoptosis in MV-4-11 and MM.1S cell lines. YTHu78 demonstrates significant antiproliferative activity against various hematologic tumor cell lines and is useful for studying hematological malignancies.

PZ671 is a potent PROTAC degrader targeting Bcl-xL, exhibiting an IC50 of 1.3 nM in MOLT-4 cells and a DC50 of 0.9 nM for Bcl-xL. It induces apoptosis in MOLT-4 cells and effectively inhibits tumor growth in MOLT-4 xenograft mice, while quickly restoring transiently reduced platelet counts. PZ671 is applicable in cancer research, including studies on small cell lung cancer.

Apo A-I mimetic 5A peptide is a synthetic peptide molecule designed based on the structure and function of naturally occurring apolipoprotein A-I (Apo A-I). It facilitates the efflux of cholesterol from inside cells, helping to reduce intracellular cholesterol accumulation. Additionally, Apo A-I mimetic 5A peptide exhibits anti-inflammatory properties, lowering inflammatory markers in blood and tissues. This peptide is used in cardiovascular disease research.

PD-1/PD-L1-IN-40 (Compound EP16) is a PD-1/PD-L1 inhibitor. It effectively suppresses the production of exosomal PD-L1 with an IC50 of 0.108 μM. PD-1/PD-L1-IN-40 serves as a lead compound for the elimination of exosomal PD-L1 and is applicable in cancer research.

M7GpppAmpG is a trinucleotide 5′ cap analog, exhibiting capping efficiencies of 90% for the produced RNAs [1].

Ferroptosis-IN-20 (Compound 34a) is an inhibitor of ferroptosis targeting voltage-dependent anion channels (VDAC) with an EC50 of 24.2 nM. It prevents VDAC oligomerization and lipid peroxidation. Additionally, Ferroptosis-IN-20 reduces ROS levels, diminishes TFR1-mediated iron uptake, inhibits Fe2+ levels, and restores glutathione (GSH) levels. It also alleviates acute kidney injury (AKI) caused by folic acid.

Garlic oil can inhibit lung tumors caused by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) by inducing second-phase drug metabolizing enzymes.

GSNOR-IN-1 is a prodrug of GSNOR-IN-2 and functions as an S-nitrosoglutathione reductase (GSNOR) inhibitor capable of crossing the blood-brain barrier. GSNOR-IN-1 offers significant protective effects against damage induced by oxygen-glucose deprivation/reoxygenation (OGD/R). It regulates calcium signaling and synaptic function through Clstn1 S-nitrosylation and inhibits neuronal apoptosis. Additionally, GSNOR-IN-1 markedly reduces infarct volume in rat models of ischemic stroke while enhancing neurological function. With its neuroprotective properties, GSNOR-IN-1 holds potential for ischemic stroke research.

IBI-325 is a humanized monoclonal antibody inhibitor targeting CD73. It completely inhibits CD73 enzymatic activity without causing a hook effect. IBI-325 can reverse adenosine monophosphate-mediated immunosuppression and significantly inhibits T cell proliferation and the release of cytokines (IL-2, IFN-γ, and TNF-α). In both hPBMC-reconstituted mouse models and hCD73 knock-in mouse models, IBI-325 demonstrates potent antitumor activity. This compound is applicable for cancer immunotherapy research.

PROTACPI3Kδ degrader-1 is a covalent PI3Kδ-targeting PROTAC degrader that targets lysine, with a DC50 of 3.98 nM. It exhibits potent antiproliferative activity and selective PI3Kδ inhibition (IC50: 8 nM). Additionally, PROTACPI3Kδ degrader-1 effectively degrades p-AKT, induces cell cycle arrest in the G1 phase, and promotes apoptosis and autophagy. It also significantly suppresses tumor growth in the SU-DHL-6 xenograft mouse model.

HMGB1-IN-2 (compound 15) is a selective inhibitor of the highly conserved nuclear protein HMGB1, demonstrating no inhibitory effect at an IC50 of 20.2 μM in

Fosimdesonide, a small molecule analog of adalimumab, serves as a potent immunomodulator with demonstrated anti-inflammatory activity [1].

Roxatidine, a metabolite of Roxatidine acetate, is a H2-receptor antagonist that prevents ulcers and has anti-inflammatory properties.

Perfluorodecanoic acid is a biochemical.

GNE-1567 is a potent ERα PROTAC degrader and a selective antagonist of XIAP, with a Kd of 0.03 μM. It is applicable in breast cancer research.

Biotin-DEVD-CHO (TFA) is the biotin-conjugated form of the caspase-3 and caspase-7 inhibitor Ac-DEVD-CHO. It can be utilized for affinity purification of active caspase-3, -6, -7, and -8 and is also applicable for in vitro detection of active caspase-3.

[Ru(DIP)2TAP]Cl2, a Ruthenium(II) polypyridyl compound, serves as a photosensitizer and is utilized in photodynamic therapy (PDT) research.

L-Glutamic-5-14C acid is a bioactive chemical.

Eps8 peptide 327 is an HLA-A*2402-restricted peptide antigen derived from the Eps8 protein. It exhibits potent antitumor activity and significant cytotoxicity. Eps8 peptide 327 effectively inhibits cancer cell proliferation, induces apoptosis, and disrupts the EGFR signaling pathway by inhibiting the expression of downstream signals such as IL-2, TNF-α, and IFN-γ, as well as impeding the Eps8/EGFR interaction. It significantly suppresses tumor growth in HT-29 xenograft models.

Tubulin polymerization-IN-79 (Compound C20) acts as an inhibitor of microtubule polymerization. It exhibits significant antiproliferative activity against esophageal cancer cells, such as KYSE450 (IC50=0.36 μM) and EC-109 (IC50=0.63 μM). In esophageal cancer cells, Tubulin polymerization-IN-79 occupies the colchicine binding site, disrupting the microtubule network's integrity, activating the Hippo signaling pathway, downregulating the oncogenic protein YAP, and inducing G2/M phase arrest and apoptosis. This compound shows promise for esophageal cancer research.

Halleridone, a natural product, is identified in Teuanchum decipiens and Abeliophyllum distichum.

BTK ligand 12 is a PROTAC target protein ligand serving as an active control for NRX-0492 (a BTK degradator).

MB-314 is a humanized IgG1 monoclonal antibody (mAb) targeting Lewis Y. This compound enhances antibody-dependent cell-mediated cytotoxicity (ADCC) activity and increases the release of IFN-γ, TNF-α, MCP-1, and IL-6. MB-314 is applicable in cancer research.

Bcl-2-IN-23 (compound 5) is a selective inhibitor targeting Bcl-2. It demonstrates an IC50 range of 25.7-33.7 μM in HTB-140, HeLa, and SW620 cells. Acting through non-covalent competitive binding to the Bcl-2 protein, Bcl-2-IN-23 significantly reduces Bcl-2 expression, inducing late-stage apoptosis and necroptosis in cancer cells. By disrupting the Bcl-2-mediated mitochondrial apoptotic inhibition pathway, it increases cancer cell susceptibility to apoptosis and reduces the release of the inflammatory factor IL-6. Bcl-2-IN-23 is applicable in anti-apoptosis research for malignant tumors such as melanoma, cervical cancer, and colorectal cancer.

Mcl-1 inhibitor 3 shows good pharmacokinetic properties and excellent in vivo efficacy without toxicity.Mcl-1 inhibitor 3 is a highly potent and orally activate

L 683519 is one of the Tacrolimus impurities with immunosuppressant and could restrain the activity of FK-506 binding protein.

CSN5-IN-1 (compound Ac-11) serves as an inhibitor of CSN5, exhibiting IC50 values of 12.56 μM in FP assay and 19 μM in fluorescence assay. Additionally, it influences cellular protein expression by downregulating PD-L1 and upregulating NEDD8-Cul1.

5-hydroxy Diclofenac, a CYP3A4-formed NSAID diclofenac metabolite, inhibits COX-1/2 with varying IC50 values.

TrxR-IN-7 (14f) is a potent inhibitor of thioredoxin reductase (TrxR), with an IC50 value of 3.5 µM. It exhibits antiproliferative activity and can induce apoptosis and the production of reactive oxygen species (ROS).

Antioxidant agent-20 (Compound 3d) exhibits potent anti-inflammatory and antioxidant activities. It reduces reactive oxygen species (ROS) and apoptosis in a dose-dependent manner. Antioxidant agent-20 demonstrates photoprotective effects on UVB-exposed human skin keratinocytes (HaCaT) (IC50=5.13 µM) by activating Nrf2/HO-1 signaling and inhibiting the NF-κB pathway.

Mitochondria modulator-2 (Compound Ir1) induces depolarization of the mitochondrial membrane potential, generates reactive oxygen species (ROS), inhibits the migration of A549 cells, causes cell cycle arrest at the G2/M phase, and triggers apoptosis in A549 cells.

FLT3-IN-28 (Compound 12y) is an orally active FLT3 inhibitor with antitumor properties. It selectively targets cancer cells with FLT3 internal tandem duplication (ITD) mutations, demonstrating IC50 values of 85, 290, 130, 65, and 220 nM against BaF3-FLT3-ITD, BaF3-TEL-VEGFR2, MV4-11, MOLM-13, and MOLM-14 cell lines, respectively. These lines include acute myeloid leukemia (AML) cells harboring FLT3-ITD mutations such as MV4-11 and MOLM-13/14. The compound also reduces phosphorylation levels of FLT3 and STAT5 in MOLM-13 cells, leading to cell cycle arrest and apoptosis. With an oral bioavailability of 19.2% in SD rats, FLT3-IN-28 extends survival in a dose-dependent manner in MOLM-13 xenografted NSG mouse models. It holds promise for research in FLT3-ITD-related cancer studies.

Biguanidinium-porphyrin free TFA is a mitochondrial-targeting photosensitiser exhibiting low dark toxicity towards human hepatocellular carcinoma HEp2 cells.

Emavusertib Tosylate (also known as CA-4948) is a potent inhibitor of IRAK4/FLT3 with demonstrated antitumor activity. In cell lines such as ABC DLBCL and AML, CA-4948 exhibits strong cellular efficacy. Among 329 evaluated kinases, it shows medium to high selectivity. The compound has excellent oral bioavailability and favorable pharmacokinetic properties in ADME and PK profiles. In preclinical models involving mice, rats, and dogs, CA-4948 demonstrated good oral bioavailability and displayed over 90% tumor growth inhibition in relevant tumor models, correlating well with in vivo pharmacodynamic regulation.

EP5-1 is an antimicrobial peptide with antibacterial, antifungal, antitumor, and antiviral properties, notably inducing apoptosis in cancer cells and

PD-L1degrader-2 (Compound B3) is an orally effective AUTAC degrader that degrades PD-L1 via the autophagy-lysosome pathway with a DC50 of 0.5 μM. It inhibits the interaction between PD-1 and PD-L1, with an IC50 of 22.8 nM. PD-L1degrader-2 upregulates the expression of Atg9b, Lamp1, and Mitf, activating the autophagy-lysosome system. It exhibits antitumor activity in the CT26 mouse model.

Disitertide (P144) is a TGF-β1 receptor blocker, PI3K inhibitor, and apoptosis inducer.

NSC 15830 (S-(1,2-Dichlorovinyl)-L-cysteine) hydrochloride is a nephrotoxic compound that serves as a metabolite of trichloroethylene. This compound is capable of inhibiting TNF-α stimulated by pathogens.