Apoptosis

ZLMT-12: tacrine derivative, inhibits CDK2/CDK9, weak on AChE/BuChE, anti-proliferative, low toxicity, blocks S/G2/M phase, induces apoptosis.

EGFR/HER2-IN-6 is a dual inhibitor of EGFR, HER2, and DHFR with IC50s: 0.122, 0.078, and 0.585 μM, showing anticancer potential and selectivity.

SL-176, a WIP1 inhibitor, when combined with GSK-J4, can induce cell cycle arrest and apoptosis (apoptosis), thereby inhibiting tumor growth both in vitro and in vivo.

LSD1-IN-21: potent LSD1 inhibitor, crosses blood-brain barrier, IC50 of 0.956 μM; lowers TNF-α, anti-cancer, anti-inflammatory.

Thalidomide-O-PEG4-amine TFA is a synthetic E3 ligase ligand-linker conjugate, composed of a cereblon ligand derived from Thalidomide and a single linker.

<p>Topoisomerase I/II inhibitor 3 suppresses cell growth and induces apoptosis in liver cancer by blocking PI3K/Akt/mTOR.</p>

Compound B6, also known as TOPOI/PARP-1-IN-1, is a dual inhibitor targeting TOPOI and PARP, exhibiting low cytotoxicity and oral activity with a PARP1 IC 50 of 0.09 μM. This compound effectively inhibits cancer cell proliferation and migration, induces cell cycle arrest at the G0/G1 phase, and triggers apoptosis. In murine models, TOPOI/PARP-1-IN-1 demonstrated a tumor growth inhibition rate (TGI) of 75.4% [1].

ASK1-IN-7 (Compound 4c) is an ASK1 inhibitor and a derivative of the ASK1 inhibitor scaffold 5-(5-Phenyl-furan-2-ylmethylene)-2-thioxo-thiazolidin-4-one. This compound is potentially applicable in research involving ASK1 signaling pathways, including studies on cellular stress response, inflammatory response, neurodegenerative diseases, and cardiovascular diseases.

Ran-IN-1 (Compound M36) is an orally active and selective inhibitor of Ran GTPase. It binds allosterically with high specificity to the switch II pocket of GDP-bound Ran (RanGDP), stabilizing its inactive state and reducing the formation of active Ran-GTP. Ran-IN-1 induces apoptosis in epithelial ovarian cancer (EOC) cells and inhibits DNA repair pathways such as homologous recombination (HR) and non-homologous end joining (NHEJ). This compound shows potential for research in epithelial ovarian cancer, particularly in high-grade serous carcinoma.

CDK-IN-9: A potent CDK inhibitor, gels to enhance CDK12/DDB1 binding, targets CDK2/E (IC50: 4 nM), induces apoptosis via dephosphorylation.

<p>NLRP3-IN-26 (compound 15Z), with an IC50 of 0.13 μM, functions as an inhibitor of NLRP3. It is applicable in studies involving the DSS-induced colitis model [1].</p>

Z-VA-DL-D-FMK (Z-VA-DL-D(OH)-FMK) acts as an inhibitor of caspases. It irreversibly binds to caspases, enhancing the sensitivity to TNF-α and stimulating HIV replication in infected T cells ACH-2.

<p>ASP9831 is an orally active PDE4 inhibitor. It suppresses LPS-induced TNF-α production and exhibits anti-inflammatory properties. ASP9831 is useful in the study of steatohepatitis.</p>

Topoisomerase IIα-IN-4 (F2) is a non-intercalative ATP-competitive inhibitor of human DNA topoisomerase II, specifically inhibiting TopoIIα with an IC50 value

<p>Z-VAD is an irreversible pan-caspase inhibitor, suppressing multiple caspases including caspase-3, -6, -7, -8, and -9. Z-VAD induces autophagy in tumour cells.</p>

Topo I-IN-1 (14d) is a powerful Topo I inhibitor with antitumor effects and DNA intercalation, inducing apoptosis.

AKN-028 acetate: an oral TK inhibitor for AML research, targets FLT3 with IC50 of 6 nM, inhibits autophosphorylation, and induces apoptosis.

Ivaltinostat (CG-200745) is an oral panHDAC inhibitor, inducing apoptosis and enhancing cancer drug sensitivity.

Antitumor agent-77 suppresses cancer cell growth, migration, induces apoptosis, and hinders EMT.

BRD-K56819078, a Bcl-2 inhibitor, significantly reduces the burden of senescent cells and the mRNA expression of aging-related genes in the kidneys. It exerts its anti-aging effects by inhibiting cell apoptosis (apoptosis).

Bcl-2-IN-3 (Compound 10) is an inhibitor of Bcl-2, utilized in cancer research.

Etalocib (LY293111) sodium is an orally active leukotriene B4 (LTB4) receptor antagonist with a Ki value of 25 nM for inhibiting [3H]LTB4 binding. It exhibits an IC50 of 20 nM against LTB4-induced calcium mobilization. Additionally, Etalocib sodium can induce apoptosis.

ABL-L is able to induce apoptosis in human laryngeal cancer cells using a p53-dependent pathway.

HDAC/PSMD14-IN-1 is a derivative of gambogic acid. It serves as an orally active dual inhibitor targeting PSMD14 and HDAC1, with IC50 values of 238.7 nM and 141.2 nM, respectively. The compound exhibits significant cytotoxicity against ESCC cell lines (IC50: 30-250 nM) and effectively reverses epithelial-mesenchymal transition (EMT). Additionally, HDAC/PSMD14-IN-1 can induce apoptosis. In KYSE30 cell xenograft models in mice, it displays antitumor activity. HDAC/PSMD14-IN-1 is useful for researching esophageal cancer treatment.

YW3-56: PAD2 & PAD4 inhibitor (IC50 = 0.5-5 μM), halts U2OS cell growth (IC50 ~2.5 μM), reduces S-180 & MDA-MB-231 tumor growth in mice.

p53 Activator 8 (compound 5), a potent p53 activator, exhibits significant anti-proliferative effects on MCF7 breast cancer cell lines, demonstrating an IC 50 value of 0.5 μM [1] [2].

Antitumor agent-42 inhibits microtubule multimerisation and NO release, exhibiting anti-angiogenic, colony-forming and apoptosis-inducing effects.

PBX-7011, an active camptothecin derivative, binds to the DDX5 protein in cells and induces cell death through DDX5 protein degradation [1].

PLK1-IN-13 is a selective, orally active PLK1 inhibitor with an IC50 of 0.27 nM. It also inhibits PLK2 (IC50: 12.72 nM) and PLK3 (IC50: 4.12 nM). PLK1-IN-13 induces cell cycle arrest at the G2 phase, promotes apoptosis, and downregulates the transcription of the cancer-associated oncogene c-MYC. This compound inhibits tumor growth and is applicable for research in acute myeloid leukemia (AML).

p53 Activator 14 (Compound 7A) is a derivative of Neratinib that can induce DNA damage and activate p53, thereby inhibiting the proliferation of various cancer cells, with an IC50 of 7.21 μM for HCT116 cells. This compound hinders adhesion, migration, and invasion of HCT116 cells, disrupts the cell cycle, and triggers apoptosis. In addition, p53 Activator 14 exhibits anti-tumor properties and inhibits angiogenesis in the chick embryo chorioallantoic membrane (CAM) model.

<p>MB710 is an amino-benzothiazole derivative that tightly binds to the Y220C pocket and stabilizes p53-Y220C in vitro.</p>

FHND5071 (1H) is a selective inhibitor of RET (rearranged during transfection) tyrosine kinase. It shows potential for research applications in RET-driven cancers, such as thyroid and lung cancer.

<p>GGTI298 is a potent GGTase I inhibitor; IC50 3μM for Rap1A, &gt;20μM for Ha-Ras.</p>

MI-888 (TFA) is an orally active inhibitor of the MDM2-p53 interaction with a Ki of 0.44 nM. It can induce rapid, complete, and durable tumor regression in xenograft mouse models.

Ferroptosis-IN-6 is an efficient ferroptosis inhibitor, protecting cells from cell death induced by ferroptosis inducers, and inhibiting STY-BODIPY oxidation.

t9,t11,c15-CLNA is an isomer of conjugated linolenic acid (CLNA) produced by Lactobacillus plantarum ZS2058. It exhibits key activities including anti-inflammatory and antioxidant effects, as well as enhancement of intestinal barrier function. The regulatory mechanisms of t9,t11,c15-CLNA involve the upregulation of tight junction proteins, the inhibition of pro-inflammatory cytokines (such as TNF-α, IL-6), and the activation of antioxidant enzymes (such as SOD, CAT). t9,t11,c15-CLNA can be utilized in research on inflammatory bowel disease (like colitis).

NPB-1575 is a potent, orally active anti-inflammatory agent capable of crossing the blood-brain barrier. It mitigates neuroinflammation and resists ferroptosis by activating IRS2/Nrf2/NF-κB. NPB-1575 protects against cerebral ischemic injury and improves neurological function outcomes, making it suitable for research in focal ischemic stroke.

Antitumor agent-51 targets osteosarcoma with 21.9 nM IC50, high selectivity, and low toxicity.

eIF4A-IN-1 is an eIF4A inhibitor used in tumor research.

Metamizole (Dipyrone) hemimagnesium is an anti-inflammatory and antioxidant compound known for its ability to reduce fever. It decreases levels of C-reactive protein (CRP) and interleukin 6 (IL-6). Additionally, Metamizole hemimagnesium acts as an orally active cyclooxygenase (COX) inhibitor, suppressing cell proliferation and promoting apoptosis. It is utilized in the study of inflammation and fever.

<p>Potent oral XIAP/cIAP1 inhibitor with EC50s: XIAP 5.1 nM, cIAP1 0.32 nM; curbs tumor growth in vivo.</p>

Neral, a monoterpenoid compound, exhibits anti-inflammatory and anticancer activities. It inhibits TNF-α and IL-6, along with inflammatory mediators such as pro-IL-1β, iNOS, COX-2, and NLRP-3.

Anticancer agent 46, potent and selective, induces apoptosis, is cytotoxic to cancer cells, with low toxicity to human lymphocytes.

Neuroprotective agent 11 (Compound 1a) is an orally active polyphenolic compound that offers significant protection against cerebral ischemia. Its primary activities include inhibiting neuronal inflammation and apoptosis, reducing cerebral infarct size, and improving behavioral symptoms in mice with cerebral ischemia. The mechanism involves downregulating inflammatory factors (iNOS, COX-2) and apoptotic proteins (cleaved-Caspase3, p53). Neuroprotective agent 11 is applicable for research in ischemia-related brain diseases, such as ischemic stroke.

TP-030-1, RIPK1 inhibitor: K(i) hRIPK1 at 3.9nM, IC50 mRIPK1 at 4.2μM; targets inflammation, neurodegeneration research.

Minnelide treats pancreatic cancer, hinders androgen-related prostate growth, shrinks tumors, and improves survival.

HDAC-IN-9, a dual tubulin/HDAC inhibitor, impedes A549 cell invasion/migration and shows strong anti-tumor/angiogenic effects.

GQN-B37-E is an effective selective binder and inhibitor of MCL-1. It binds to the BH3-binding domain of MCL-1. GQN-B37-E demonstrates binding affinity for MCL-1 within the sub-micromolar range (Ki= 0.6 μM), yet shows negligible binding to BCL-2 or BCL-XL.

HDAC6/HSP90-IN-2, a cancer research chemical, inhibits HDAC6 & Hsp90 with IC50s of 105.7 & 61 nM.

BRD1991 is a chemical compound that specifically disrupts the interaction between Beclin 1 and Bcl-2, thereby inducing autophagy.

MTX-216 is an ATP-competitive inhibitor targeting both PI3K and EGFR. It simultaneously inhibits Ki-67 and ribosomal S6 phosphorylation, inducing apoptosis in NF1LOF cells. Additionally, MTX-216 suppresses SYK kinase activity with an IC50 of 281 nM. This compound is applicable for melanoma research.

Antitumor agent-76 is a water-soluble, orally active, rapid-release prodrug of Triptolide that exhibits anticancer effects.

JH-XVII-10: potent, oral DYRK1A/B inhibitor (IC50: 3/5 nM), shows antitumor activity in HNSCC.

SF-9-2 is a PD-L1/PD-1 binding inhibitor with an IC50 of 24.9 nM. It suppresses epithelial-mesenchymal transition, migration, invasion, and proliferation of SK-N-SH cells, while also inducing apoptosis and causing cell cycle arrest. SF-9-2 blocks PD-L1-induced growth of SK-N-SH cells via the MAPK signaling pathway. It restores GSK-3β activity and enhances PD-L1 degradation through the ubiquitin-proteasome pathway. In the SK-N-SH NOG mouse model, SF-9-2 inhibits tumor growth without notable toxicity. Additionally, SF-9-2 acts as an immune checkpoint inhibitor, blocking PD-L1 to restore T cell function and is applicable to neuroblastoma research.

RIPK2-IN-6 (Compound 15a) is an inhibitor of RIPK that specifically targets the phosphorylation of RIPK2, thereby suppressing the NF-κB and MAPK signaling pathways. It has demonstrated anti-inflammatory and anti-fibrotic activities in a mouse model of colitis induced by Dextran sodium sulfate.

Anticancer agent 14: a potent breast cancer inhibitor; induces cell death, disrupts mito. membrane potential (IC50: 0.20-0.65 μM).

Multi-kinase-IN-1, a powerful kinase inhibitor, exhibits antitumor properties by inducing cell apoptosis.

SphK1-IN-2: SphK1 inhibitor, IC50: 19.81 nM; less effective on SphK2. Induces apoptosis, hinders cancer cell growth.

Triphen diol, a phenol diol, fights pancreatic cancer & cholangiocarcinoma, inducing apoptosis via caspase-dependent & -independent paths.

TP-030-2 is a RIPK1 inhibitor (human K i =0.43 nM ; mouse IC 50 =100 nM) .

Flizasertib is a serine/threonine kinase inhibitor that acts by inhibiting RIPK1, which has anti-inflammatory and therapeutic effects on immune disorders.

ZLHQ-5f inhibits CDK2/Topo I, with IC50 of 0.145μM for CDK2/CycA2, and promotes apoptosis by arresting HCT116 cells in S phase.

Scytonemin, a cyanobacterial pigment, inhibits cancer cell growth by decreasing Plk1 activity, especially effective on U266 myeloma cells.

BTK-IN-7 is a potent inhibitor for BTK with 4.0 nM IC50, highly selective over ITK and EGFR, showing strong antitumor activity.

AK 295, also known as CX 295, is a dipeptide inhibitor of alpha-ketoamide calpain.

MA242 free base is a dual MDM2/NFAT1 inhibitor that triggers apoptosis in pancreatic cancer cells.

MLS-0053105, a chloromaleimide, functions as a selective inhibitor of BFL-1, exhibiting an IC50 of 0.4 µM against Bfl-1/F-Bid. Its inhibitory potency is over tenfold lower for Bcl-W, Bcl-2, and Bcl-XL, and it shows no activity against Bcl-B and Mcl-1.

Compound 5a, an anticancer agent, enhances P53 and has antiproliferative effects.

PARP1/BRD4-IN-2, a potent inhibitor of PARP1 and BRD4, halts cell cycle, triggers apoptosis, and has antitumor effects on TNBC.

FKBP12 PROTAC dTAG-13 is a PROTAC and selective degrader for target validation by splicing FKBP12 F36V with CRBN and thereby degrading FKBP12 F36V.

ERK1/2 inhibitor 11 (compound L6) is a dual inhibitor of ERK1/2 that promotes the accumulation of DSBs and the degradation of ERK1/2 expression. This compound decreases BCL-2 levels and induces DNA damage by inhibiting PARP and ERK1/2. Additionally, ERK1/2 inhibitor 11 activates caspase 3 to induce apoptosis.

Ferrostatin-1 diyne (Fer-1 diyne) (compound 2) serves as an inhibitor of ferroptosis, accumulating in cellular lysosomes, mitochondria, and the endoplasmic reticulum. It notably inhibits ferroptosis independently of lysosomal and mitochondrial activity.

EGFR-IN-47: strong oral EGFRL858R/T790M/C797S blocker, induces cell death; promising for NSCLC research. IC50: 0.01 μM.

Tandutinib (MLN518) sulfate is an effective and selective inhibitor of FLT3, with an IC50 value of 0.22 μM. It also inhibits c-Kit and PDGFR, displaying IC50 values of 0.17 μM and 0.20 μM respectively. This compound can be utilized in the treatment of acute myeloid leukemia and has the capability to cross the blood-brain barrier.

Anticancer agent 69 targets PC3 cells (IC50=26 nM), raises ROS, lowers EGFR, and induces apoptosis.

Tubulin inhibitor 14 blocks NQO2 and microtubule formation, disrupts blood vessels, and may target tumors; IC50 of 1.0 μM.

<p>Microtubulin-IN-1 (Compound 8g) is an inhibitor of microtubulin, targeting the colchicine-binding site to disrupt tubulin integrity and induce upregulation of p53 protein expression. It exhibits antiproliferative activity across various cancer cell lines, including NCI-H460, BxPC-3, and HT-29, with IC50 values of 2.4, 1.6, and 2.07 nM, respectively. Additionally, Microtubulin-IN-1 induces cell cycle arrest at the G2/M phase and apoptosis in NCI-H460 cells.</p>

GLUT-1-IN-4 (Compound 13) is an inhibitor of the GLUT-1 glucose transporter that depends on the p53 protein. It suppresses the proliferation of various cancer cells at submicromolar IC50 levels. Additionally, GLUT-1-IN-4 can halt the cell cycle, induce oxidative stress, and promote apoptosis (cell death).

CCT369260 (compound 1), an orally active inhibitor targeting B-cell lymphoma 6 (BCL6), demonstrates anti-tumor efficacy with an IC50 value of 520 nM [1].

Ganoderic acid R: potent anticancer, induces apoptosis, cytotoxic to MDR and sensitive tumor cells.

protease-activated receptor-1 (PAR1) antagonist

<p>Microtubule inhibitor 2: potent, selective, oral, induces ferroptosis, strong antitumor effect.</p>

HER2-IN-10 is a psoralen derivative that induces apoptosis. HER2-IN-10 shows anti-breast cancer activity and light-activated cytotoxicity [1].

Compound 14 is a peptidomimetic that significantly lowers TNFα, NO, CD40, and CD86, showcasing strong anti-inflammatory effects.

STAT3-IN-9 hinders STAT3 at Tyr705, doesn't affect STAT1 Tyr701, induces apoptosis, and arrests cells in G2/M phase.

Compound 5f, a potent tubulin polymerization inhibitor (IC50 = 1.09 μM), blocks cell migration, tube formation, and has anti-angiogenic effects.

GRP78-IN-1 binds to GRP78 protein, inhibits cell growth, and triggers apoptosis in breast cancer; has -8.07 kcal/mol binding energy.

<p>ASK1-IN-8 (Compound 35) is an orally active inhibitor of apoptosis signal-regulating kinase 1 (ASK1) with an IC50 value of 1.8 nM. In a mouse liver injury model induced by Acetaminophen, ASK1-IN-8 significantly reduces plasma alanine aminotransferase (ALT) levels, offering liver protection. This compound is useful for research in liver disease-related fields.</p>

Tubulin inhibitor 13 (E27), IC50 16.1 μM, blocks tubulin polymerization, cancer cell migration, and invasion, induces apoptosis.

EGFR-IN-45: Strong EGFR/CDK2 inhibitor (IC50s: 0.4 & 1.6 μM), halts cancer cell cycle pre-G1, prompts apoptosis, also targets Topo I/II.

RET-IN-11 selectively inhibits RET (IC50: 6.20 nM), promotes apoptosis, and hinders cell proliferation and migration.

Compound 28 is a nonsteroidal VDR agonist with 690 nM potency, inducing cell cycle arrest and apoptosis in MCF-7 cells.

<p>MLKL-IN-6 (compound P28) is a mixed lineage kinase inhibitor that specifically targets the Mixed Lineage Kinase domain-like (MLKL) protein.</p>

Ferroptosis-IN-15 (compound 12) serves as an effective inhibitor of ferroptosis, exhibiting EC50 values of 0.76 μM and 0.67 μM in A375 cells and 786-O cells, respectively. It acts as a potential iron chelator and radical-scavenging antioxidant.

NCI-006, an LDH inhibitor, slows tumor growth and enhances pyruvate's role in mitochondrial metabolism.

Fosizensertib is an inhibitor of RIP-1 kinase and is used in research related to ulcerative colitis.

Rezatapopt (PC14586) is a p53 reactivator with antitumor activity for the study of locally advanced or metastatic solid tumors.

HL001 is an orally active small molecule inhibitor of cyclophilin A (CypA) and a receptor antagonist of lysophosphatidic acid 1 (LPA1). It induces cell cycle arrest and apoptosis in tumor cells via p53. By downregulating G3BP1, HL001 promotes reactive oxygen species production and DNA damage to stabilize p53. It disrupts the interaction between MDM2 and p53-72R in a CypA-dependent manner. HL001 exhibits antitumor activity and can also be used in research on pulmonary fibrosis.

Anticancer agent 64 (5m) induces apoptosis, has IC50 2.4μM in CCRF-CEM, activates caspases, cleaves PARP, affects mitochondria.

vacuolar H+-ATPases (V-ATPases) inhibitor