Apoptosis

Necrosis Inhibitor 3 (compound B3) effectively inhibits necrosis, demonstrating an IC50 of 0.29 nM in HT29 cells [1].

NiCur is an effective and selective inhibitor of CBP histone acetyltransferase (HAT), with an IC50 of 0.35 μM.

4-Bromo A23187 is a halogenated analog of the calcium ionophore A-23187. 4-Bromo A23187 is a calcium modulator and induces apoptosis in different cells.

KIRA9 inhibits IRE1 with a 4.8 μM IC50, blocking ER-stress-induced mRNA decay and apoptosis by fully binding IRE1's ATP site.

DeFer-2 is a ferritin PROTAC degrader (Kd= 17.1 μM). It triggers the degradation of ferritin leading to the accumulation of free iron ions and an increase in ROS, which subsequently initiates caspase 3-GSDME mediated pyroptosis in cancer cells. DeFer-2 significantly inhibits tumor growth and extends the survival of mice with subcutaneous B16F10 tumors, and it is useful for melanoma research.

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

<p>TNF-α-IN-12, a TNF-α inhibitor with an IC50 of 0.1 μM, can reduce TNF-α blood levels [1].</p>

PD-1/PD-L1-IN-30: Cancer research inhibitor with 0.018 μM IC50.

Soquelitinib (CPI-818) is a selective ITK inhibitor， inhibits tumor growth,T-cell, up-regulatCXCR3, IFNγ, TNFα, and CD107a expression in normal CD8 cells.

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

EGFR-IN-3 is an EGFR inhibitor with antitumor activity.EGFR-IN-3 inhibits EGFRwt-TK, induces apoptosis (cell death), and can block cells in the G2/M phase.

YK5 is an allosteric inhibitor pocket of Hsp70 and represents a previously unknown chemical tool to investigate cellular mechanisms associated with Hsp70.

GL0388, a Bax activator, induces apoptosis, hinders breast cancer growth, and has IC50 of 0.299-1.57 μM.

PKM2-IN-6 (compound 7d) is an orally active PKM2 inhibitor (IC50=23 nM) capable of inducing apoptosis and G2 cell cycle arrest. It reduces PKM1 and PKM2 expression at the mRNA level, exhibits antitumour activity, and is suitable for investigating triple-negative breast cancer (TNBC).

RIPK1-IN-23 (compound 19) is an RIPK1 inhibitor with potent anti-necroptotic effects in HT-29 cells (EC50 = 1.7 nM). Additionally, RIPK1-IN-23 exhibits anti-inflammatory properties.

<p>tDHU, acid is a dihydropyrimidine cereblon ligand consisting of an E3 ligase ligand and a benzoic acid linker. It serves as an E3 ubiquitin ligase ligand-linker conjugate in the development of PROTACs.</p>

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

QTX125 TFA: Potent, selective HDAC6 inhibitor with antitumor effects.

Verrucarin A, a mycotoxin from Myrothecium verrucaria, inhibits protein synthesis, leukemia growth, and triggers apoptosis.

<p>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>

CDK4/6-IN-10: Oral CDK4 (IC50: 22 nM) & CDK6 (IC50: 10 nM) inhibitor with anti-cancer potential for MM research.

Rafutrombopag is a thrombopoietin (TPO) agonist.

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).

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

<p>Thalidomide-NH-amido-PEG2-C2-NH2 is a synthetic E3 ligase ligand-linker conjugate comprising a Thalidomide-based cereblon ligand and a linker. It is utilized in the synthesis of PROTACs.</p>

<p>Coumarin 9a: Selective inhibitor of hCA IX/XII (Ki 93.3/85.7 nM), blocks cancer cell growth, and induces apoptosis.</p>

<p>Sinulatumolin E, a terpenoid, inhibits TNF-α (IC 50: 3.6 μM); has anti-inflammatory properties.</p>

Antitumor Agent-184 (compound 12aa) triggers apoptosis in various cell lines, exhibiting IC50 values of 2.35 μM in B16-F10 cells, 7.32 μM in 4T1 cells, and 10.31 μM in CT26 cells.

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

OICR12694 (JNJ-65234637) is an orally active inhibitor of B cell lymphoma 6 (BCL6) .

Cofpropamine, a caffeine derivative that inhibits polyadenylation, enhances the suppressive effects of Cyclophosphamide in animal models of rat adjuvant arthritis and mouse collagen-induced arthritis.

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

Topo II/HDAC-IN-1 (7d) demonstrates potent dual inhibitory effects on Topo II and HDAC, while Topo II/HDAC-IN-1 (8d) effectively induces apoptosis [1].

Z-3578 is a small molecule antagonist targeting the MrgX2 (Mas-related G protein-coupled receptor X2) with notable anti-pseudoallergic properties, exhibiting a KD value of 729 nM. It effectively inhibits mast cell degranulation induced by substance P (SP) and C48/80, with IC50 values of 4.90 µM and 6.18 µM, respectively, suppresses the release of β-hexosaminidase, and significantly reduces the release of histamine and TNF-α, as well as intracellular calcium flux. Additionally, in a mouse pseudoallergy model, Z-3578 significantly alleviates foot swelling, dye leakage, and reduces serum histamine levels, indicating a strong in vivo anti-allergic effect. Z-3578 presents as a promising lead compound in the field of anti-allergic treatments, particularly for pseudoallergic reactions.

CK156 inhibits DAPK with high selectivity; IC50: 182 nM (DRAK1), 34 μM (CK2a1), 39 μM (CK2a2); key in autoimmune/inflammation research.

<p>AQIM-I is a survivin inhibitor that reduces survivin expression and colony formation. It promotes reactive oxygen species (ROS) production, apoptosis, cell cycle arrest, DNA damage, and autophagy. Moreover, AQIM-I effectively inhibits nonsmall cell lung cancer cells A549, with an IC 50 value of 9 nM [1].</p>

RET-IN-7 exhibits strong inhibitory effects against RET kinase in vitro and shows significant efficacy in treating RET-driven tumor xenografts in mice through

D-Cl-amidine hydrochloride is a potent and highly selective inhibitor of PAD1. It exhibits excellent tolerance and does not induce significant toxicity [1].

<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>

Bcl-2-IN-7 inhibits Bcl-2, encourages apoptosis in cancer cells, and has anti-tumor activity with various IC50 values.

Pan-Trk-IN-3: potent Trk inhibitor (IC50: 2-26 nM), effective against drug-resistant mutants, induces apoptosis, anti-tumor effects.

<p>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.</p>

VEGFR-2-IN-15 (Compound 14b) is a potent inhibitor of VEGFR-2. VEGFR-2-IN-15 inhibits the growth of HepG2 cells in the Pre-G1 phase and induces apoptosis.

Nenocorilant (Relacorilant) is an orally active glucocorticoid receptor (GR) antagonist (Ki: 0.15 nM). Nenocorilant can be used to study tumours.

TFCP2L1-IN-1 is a TFCP2L1 transcription factor inhibitor that regulates cell proliferation and promotes antitumor effect of Sorafenib by STAT3/NANOG pathway.

JR5-26B is an orally active apoptosis (apoptosis) inducer. It induces cell death via copper-mediated apoptosis and necroptosis (necroptosis). JR5-26B exhibits antiproliferative activity against MIA PaCa-2, PANC-1, PAN02, SU.86.86, and KPC-2 cells, with IC50 values of 0.6, 4.4, 8.0, 1.1, and 3.4 μM, respectively.

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

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

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

STAT3-IN-12,STAT3 signaling inhibitor. Blocks IL-6-induced JAK/STAT3 activation. Induces apoptosis. Used in HCC and esophageal cancer research.

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).

PI4KIII beta inhibitor 4 (Compound 16) is a selective inhibitor of PI4KIIIβ with an IC50 of 0.005 μM. By inhibiting the PI3K/AKT pathway, PI4KIII beta inhibitor 4 induces apoptosis, causes cell cycle arrest, and triggers autophagy in tumor cells. This compound is applicable for tumor research.

<p>eIF4E-IN-4 (Compound 33) is a selective inhibitor of the eukaryotic initiation factor 4E (eIF4E) with a biochemical activity value of 95 nM. It inhibits cap-dependent mRNA translation with an IC50 of 2.5 μM and is applicable in research on breast cancer, colon cancer, and head and neck cancer.</p>

NSC308848 is an effective apoptosis (cell death) inducer that operates in a Myc-dependent manner. It acts by inhibiting Myc transactivation and disrupting the DNA binding activity of Myc family proteins.

TNF-α-IN-2 is orally active TNFα inhibitor that distorts the TNFα trimer, causing abnormal signal transduction when it binds to TNFR1, rheumatoid arthritis.

RIP3 Activator 1 (compound C8) is an effective RIP3 activator that inhibits cell growth and induces necroptotic cell death (necroptosis) and autophagy through the RIP3/p62/Keap1 signaling pathway. Additionally, this compound enhances the expression of p-MLKL and promotes the accumulation of LC3-II and p62 proteins.

Anticancer agent 16 showed good cytotoxic effects on HCT-116 cell line (IC50: 8.55 μM), NCI-H460 cell line (IC50: 5.41 μM) and SKOV3 cell line (IC50: 6.4 μM).

HER2-IN-11 is a psoralen derivative that induces apoptosis. HER2-IN-11 shows light-activated cytotoxicity and also exhibits anti-breast cancer activity [1].

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.

Vitamin K5 (hydrochloride), a naphthoquinone compound, exhibits trichomonacidal activity in vitro and can be utilized for anti-infection research [1].

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

ADAR1-IN-1 is a potent ADAR1 inhibitor. It significantly suppresses the proliferation of DU-145 cells (IC50 = 1.11 μM), inhibits colony formation, migration, and invasion, and induces cell cycle arrest and apoptosis. ADAR1-IN-1 effectively and safely impedes tumor growth and can be utilized in prostate cancer (PCa) research.

Dicycloplatin is an inducer of DNA damage. It activates doubly phosphorylated checkpoint kinase 2 (CHK2), breast cancer 1 (BRCA1), and triply phosphorylated p53 to induce DNA damage. Dicycloplatin can cause cell cycle arrest, inhibit proliferation, and trigger apoptosis in prostate cancer PC3 cells and lung cancer NCI/H446 cells. It is applicable for research in the field of cancer.

CIL-102 is an apoptosis inducer that functions as an MMP-2/MMP-9 inhibitor, effectively reducing both the protein expression and mRNA levels of MMP-2/MMP-9. CIL-102 also demonstrates anticancer activity.

SM-433 hydrochloride, a Smac mimetic & IAP inhibitor, binds XIAP BIR3; potent IC50 <1 μM. (Patent WO2008128171A2)

Aplysin suppresses breast cancer cells and protects liver cells by blocking PI3K/AKT/FOXO3a and preventing oxidative damage.

Anticancer agent 44 induces apoptosis, is selective, cytotoxic to cancer cells, and minimally toxic to human lymphocytes.

NF-κB-IN-4 (compound 17) is a potent inhibitor of NF-κB pathway which can cross blood brain barrier (BBB).

SMO-IN-5 (Compound 25(B31)) is an effective inhibitor of smoothened (SMO), which suppresses the Hedgehog (Hh) signaling pathway. This compound inhibits cellular proliferation and induces apoptosis, demonstrating antitumor activity.

EGFR/VEGFR2-IN-3 (compound 9) is an effective inhibitor of EGFR and VEGFR-2, demonstrating IC50 values of 0.129 µM for EGFR, 0.142 µM for VEGFR-2, and 3.428 µM for COX-2. This compound exhibits cytotoxic properties and induces cell apoptosis (apoptosis) as well as cell cycle arrest at the G2/M phase.

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

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.

GLS1 Inhibitor-6: IC50=68nM, 220x more selective for GLS2, has anti-tumor and pro-apoptosis effects.

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].

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

FLT3-ITD-IN-3 (13v) is an orally active inhibitor of FLT3-ITD (internal tandem duplication of FLT3), which works by blocking FLT3 signaling. This inhibition leads to cell cycle arrest in the G0/G1 phase and induces apoptosis. The compound is currently employed in studies related to acute myeloid leukemia (AML).

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

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

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

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.

AKT-IN-3: potent oral Akt inhibitor with low hERG blockage. IC50: 1.4-1.7 nM for Akt1-3. Inhibits AGC kinases like PKA, PKC.

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

ZLWT-37: Oral CDK inhibitor, CDK9 IC50=0.002 µM, CDK2 IC50=0.054 µM; halts HCT116 cells at G2/M, induces apoptosis.

Anticancer agent 53 exhibits potent in vitro cytotoxicity, triggers apoptosis, halts S/G2/M cycle, and has antitumor effects without toxicity.

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

<p>Topo II/HDAC-IN-2 (8d) demonstrates remarkable dual inhibitory effects on Topo II and HDAC, and also induces apoptosis [1].</p>

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

Tubulin polymerization-IN-4: inhibits tubulin (IC50=4.6 μM), blocks G2/M phase, induces apoptosis, hinders cell cloning/migration, damages vasculature.

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.

Tubulin inhibitor 41 (Compd D19) is a promising lead compound for glioblastoma treatment, known for its ability to penetrate the blood-brain barrier (BBB). It functions as a tubulin inhibitor, inducing G2/M phase arrest, leading to cell apoptosis, and inhibiting the migration of U87 cells [1].

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.

GLI1-IN-1 (CBC-1), a GLI-1 inhibitor, exhibits superior water solubility and anticancer properties. It effectively induces apoptosis and inhibits colorectal cancer growth by targeting the Hedgehog (HH) pathway (IC 50 = 1.3 μM) [1].

Tubulin/NRP1-IN-1 (compound TN-2) serves as a dual inhibitor targeting both Tubulin and NRP1, exhibiting IC50 values of 0.71 μM and 0.85 μM, respectively. This compound notably reduces the viability of prostate tumor cell lines and triggers apoptosis [1].

TLBC, a borane-chalcone derivative, exhibits dose-dependent inhibitory effects across various glioma cell lines with IC50 values ranging from 5.5 to 25.5 μM. TLBC induces apoptosis independently of alterations in the tumor suppressor factor p53.

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.

Antiproliferative agent-63 (compound 4d) is a cyclic analog of cannabidiol that acts as an anticancer agent. It demonstrates favorable activity against breast and colorectal cancer. Moreover, this compound can arrest the cell cycle in the G1 phase and induce apoptosis through the mitochondrial pathway in breast cancer cell lines.

FLT3-IN-32 is a potent FLT3 inhibitor with high selectivity, effectively suppressing FLT3 activating mutations and inducing apoptosis. It demonstrates good tolerance in non-tumor-bearing mice. In NOD/SCID mice loaded with MV4-11 cells, FLT3-IN-32 exhibits outstanding antitumor efficacy, significantly extending mouse survival. FLT3-IN-32 is applicable for acute myeloid leukemia research.

Anticancer agent 17 was effective against HeLa cells (IC50: 0.19 μM) and A2780 cells (IC50: 0.09 μM).

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

(±)-Perillaldehyde exhibits antidepressant effects in mice with stress-induced depressive-like behavior by modulating the olfactory nervous system. Additionally, it demonstrates anti-inflammatory activity by activating JNK in RAW264.7 cells and suppressing the expression of TNF-α, with an IC50 value of 171.7 μM.

P53 Activator 11 (compound A-1) is a highly effective p53 activator, demonstrating an EC50 value of 0.478 µM for p53 (Y220C). It holds potential for cancer research [1].

LLW-018 is a potent PD-1/PD-L1 inhibitor with an IC50 value of 2.61 nM. It can disrupt the PD-1/PD-L1 interaction, with a cell-based PD-1/PD-L1 blocking bioassay IC50 value of 0.88 μM. LLW-018 holds potential for research in immune-related diseases.

<p>TopoisomeraseI/II inhibitor 8 (Compound Ru7) is a dual catalytic inhibitor of TopoisomeraseI/II that induces DNA damage and activates PARP-1, leading to the activation of RIPK1, RIPK3, and MLKL, ultimately causing necroptosis. It shows significant anticancer activity by effectively targeting cancer cell nuclei and inducing cell death through necroptosis, offering substantial clinical potential in overcoming resistance in cancer treatment.</p>

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.

Bim-IN-1 is a potent inhibitor of Bim expression with low toxicity, Bim-IN-1 reduces Bim expression levels with little inhibition of protein kinase A.

T-1-PMPA, a potent EGFR inhibitor, demonstrates apoptotic properties and effectively inhibits EGFR WT and EGFR 790m, with IC50 values of 86 nM and 561.73 nM, respectively [1].

Microtubule stabilizer; halts cancer cell growth (IC50: 3-30 nM); arrests cells in prometaphase; prevents bipolar spindle formation.