SW IV-52 is a pro-apoptotic small molecule SMAC mimetic and XIAP inhibitor.

SW IV-134 is a sigma-2/SMAC drug conjugate, chemically linked the sigma-2 ligand SW43 to the Smac mimetic SW IV-52.SW IV-134 slowed tumor growth and improved survival in murine models of pancreatic cancer.SW IV-134 significantly reduced tumor burden and improved overall survival in a mouse xenograft model of ovarian cancer without causing significant adverse effects to normal tissues.SW IV-134 induced degradation of cIAP-1 and cIAP-2 leading to NF-қB activation and TNFα-dependent cell death.

SN-6109 (SN6109) is a small molecule inhibitor RIPK-1 with IC50 of 0.45 uM in radiometric kinase assays.SN-6109 reduced MLKL activation EC50 2.5-11.5 uM under long-term necroptosis execution in murine fibroblast L929 cells, and full protection from ATP depletion and membrane leakage in human and murine cells.SN-6109 decreased p-MLKL/MLKL and p-RIPK3/RIPK3 ratios in mouse liver tissue, showed efficacy in an in vivo model of tissue injury and inflammation driven by RIPK1/3-dependent cell death.

SGC-STK17B-1 is a potent, selective, ATP-competitive inhibitor of death-associated protein kinase family member STK17B (DRAK2) with IC50 of 34 nM, >100-fold selectivity over STK17A; SGC-STK17B-1 is also >100-fold selective over all of the other kinases tested, with only STK17A, CAMKK1, and AURKB (IC50s=5-9 uM) in panel of 403 wild type human kinase assays. SGC-STK17B-1 demonstrated the highest cell potency in the NanoBRET target engagement assay (IC50=190 nM). SGC-STK17B-1 is the first truly potent and selective chemical probe of STK17B.

Procaspase-6 inhibitor 13 is a small molecule, noncovalent, allosteric inhibitor of procaspase-6 with KD of 0.38 uM.Procaspase-6 inhibitor 13 binds to pro-C6 at the dimer interface and contacts amino acids Y198, T199 and E214.Procaspase-6 inhibitor 13 significantly stabilizes procaspase-6.

Procaspase-6 inhibitor 12 is a small molecule, noncovalent, allosteric inhibitor of procaspase-6 with KD of 0.47 uM.Procaspase-6 inhibitor 12 binds to pro-C6 at the dimer interface and contacts amino acids Y198, T199 and E214.Procaspase-6 inhibitor 12 significantly stabilizes procaspase-6.Procaspase-6 inhibitor 12 prevents the activation of the Caspase-6 zymogen by mHTT1–586 in COS-7 cells.

PG3d (Caspase-6 inhibitor PG3d) is a cell-active, allosteric and irreversible, non-competitive Caspase-6 inhibitor.PG3d preferentially inhibits the cleavage of protein over peptide substrates both with purified proteins and in live cells.PG3d prevents the C6 (Caspase-6)-HTT interaction and prevents mHTT1-586 mediated activation of procaspase-6.PG3d specifically inhibits the cleavage of protein, but not peptide substrates of Caspase-6.

NPD4928 (NPD 4928) is a small molecule that enhances ferroptosis via inhibition of ferroptosis suppressor protein 1 (FSP1).NPD4928 enhanced the sensitivity of various cancer cells to GPX4 inhibitor RSL3.

Leusin-1 (Leukemia specific inhibitor 1) is a cell cycle phase specific inhibitor that specifically arrest leukemia cells during G2-phase and triggers an apoptotic cell death (CCRF-CEM IC50= 2.66 uM and TOM1 IC50= 0.877 uM).Leusin-1 showed specificity towards acute lymphoblastic leukemia cells than other types of leukemias, non-bloodborne cancers, or normal cells.Leusin-1 also arrested cells with lower levels of p-H3 (present only in M-phase) and increased levels of Cyclin A (levels peak in G2-phase).Leusin-1 does not target tubulin, Leusin-1 inhibited colony formation similar to Taxol.

iHPCAL1 is a ferroptosis inhibitor that effectively inhibits RSL3-induced cell death, directly interacts with HPCAL1 and significantly inhibits HPCAL1 protein expression at 1.25-5 uM in HT-1080 and Calu-1 cells.iHPCAL1 delayed thermal-induced HPCAL1 protein degradation in cellular thermal shift assays (CETSAs), failed to affect the phosphorylation of PRKCQ, but inhibited the phosphorylation of HPCAL1 as well as the autophagic degradation of CDH2 induced by RSL3.The suppression of HPCAL1 phosphorylation and function induced by iHPCAL1 occurs downstream of PRKCQ phosphorylation.Bortezomib, but not chloroquine, prevented iHPCAL1-induced HPCAL1 protein degradation, iHPCAL1 stimulates the degradation of HPCAL1 through the proteasome pathway, thereby limiting ferroptosis.iHPCAL1 inhibited the anticancer activity of Imidazole ketone erastin (IKE) in a xenograft tumor model after inoculating HT-1080 cells into athymic nude mice or in an orthotopic pancreatic tumor model in which KPC cells, with no significant effect on IKE-induced GPX4 degradation in the xenograft tumor model.iHPCAL1 (10 mg/kg) protects against ferroptosis-associated acute pancreatitis in mice.

H210 is a potent dual Mdm2/MdmX inhibitor with Ki of 9.66/2.89 nM, respectively.

GW440139B is a potent RIPK3 inhibitor, suppresses necroptosis driven by dimerizable RIPK3 with IC50 of 73.6 nM.GW440139B inhibits TNF- and TRIF-mediated necroptosis independent of RIPK1-RIPK3 interaction, directly inhibited RIPK3-mediated MLKL phosphorylation at Ser345, thus inhibiting necroptosis.

Dual DRAK1 and DRAK2 inhibitor 1 is a potent, dual DRAK2/1 inhibitor Kd value of 9/5 nM, respectively; Dual DRAK1 and DRAK2 inhibitor 1 also is a functional inhibitor of DRAK2/1 enzymatic activity with IC50 of 0.86 and 2.25 uM. Dual DRAK1 and DRAK2 inhibitor 1 is a chemical tool compound to study DRAK1 and DRAK2 biology.

D-NA-NOXA SAHB-15 R31E is a peptidic, functionally selective and cell-permeable BFL-1/A1 inhibitor that is specifically cytotoxic to BFL-1/A1-dependent human cancer cells.

CCT369347 (CCT-369347) is potent selective inhibitor of BCL-6 with TR-FRET IC50 of 26 nM.CCT369347 demonstrated antiproliferative activity in a panel of BCL6-positive lymphoma cell lines (OCI-Ly1, SU-DHL-4, and SU-DHL-6) with IC50 of 1.68-3.45 uM, with weaker activity against low BCL6 expression cells and noncytotoxocity. CCT369347 inhibits BCL6 in a cellular assay with a submicromolar IC50 and shows promising early PK.

ALRN-6924 (ALRN6924) is a potent dual inhibitor of MDM2/MDMX.ALRN-6924 demonstrated potent anti-proliferative activity in a dose-dependent manner in two ER+ cell lines with WT TP53, MCF-7 and ZR-75-1, with IC50 values of 113 nM and 500 nM respectively.The combination of ALRN-6924 and chemotherapeutic agents synergistically inhibit cell proliferation in vitro, ALRN-6924 combined with paclitaxel reactivates p53 and induces cell cycle arrest and apoptosis in vitro.ALRN-6924 mutually enhances both paclitaxel and eribulin antitumor efficacy and inhibits tumor growth in vivo.

A novel small-molecule dual inhibitor of p53-MDM2/X interactions by potentially binding to p53, without effect on other MDM; causes growth inhibition, mediated by p53 stabilization and upregulation of p53 transcriptional targets involved in cell cycle arrest and apoptosis; shows a p53-dependent antitumor activity in human tumor xenograft mice models; a novel p53 activator.

A derivative of BAM-7 that acts as a nove potent, direct activator of Bax with EC50 of 700 nM; inhibits GBM cell proliferation, arrests the cell cycle, and induces apoptosis through the induction of mitochondrial membrane permeabilization; also blocks proliferation and self-renewal of GSCs and induces their apoptosis; sensitizes both GBM cells and GSCs to the alkylating agent Temozolomide.

NSC194598 is a specific small molecule inhibitor that inhibits p53 sequence-specific DNA binding in vitro (IC50=180 nM) and in vivo.

NSC405640 is a potent inhibitor of the MDM2-p53 interaction. NSC405640 rescues structural p53 mutations. NSC405640 selectively inhibits the growth of cell lines with wild-type p53.

Mutant p53 modulator-1 is a mutant p53 modulator. Mutant p53 modulator-1 reduces the progression of cancers that contain a p53 mutation (extracted from patent WO2021231474A1, compound 231B).

PK9327 is a small-molecule stabilizer targeting cavity-creating p53 cancer mutations.

Bcl-2/Mcl-1-IN-1 (compound 3) is a Bcl-2/Mcl-1 inhibitor, with Kis of 1.19 μM and 4.53 μM for Mcl-1 and Bcl-2, respectively. Bcl-2/Mcl-1-IN-1 can be used for the research of cancer.

Bcl-2/Mcl-1-IN-2 (compound 2) is a Bcl-2/Mcl-1 inhibitor, with Kis of 0.88 μM and 4.70 μM for Mcl-1 and Bcl-2, respectively. Bcl-2/Mcl-1-IN-2 can be used for the research of cancer.

Mcl-1 inhibitor 7 is a potent Mcl-1 inhibitor, example 35, extracted from patent WO2020097577A.

Bcl-2/Mcl-1-IN-3 (compound 1) is a Bcl-2/Mcl-1 inhibitor, with Kis of 0.14 μM and 0.23 μM for Mcl-1 and Bcl-2, respectively. Bcl-2/Mcl-1-IN-3 can be used for the research of cancer.

ISIS 104838 is an antisense oligonucleotide drug that reduces the production of tumor necrosis factor (TNF-alpha), a substance that contributes to joint pain and swelling in rheumatoid arthritis.

RIPK1-IN-10 is a potent RIPK1 inhibitor, example 37, extracted from patent WO2021160109.

RIPK1-IN-11 is a potent and orally active RIPK1 inhibitor (Kd=9.2 nM; IC50=67 nM). RIPK1-IN-11 inhibits necroptosis in both human and mouse cells (EC50=17-30 nM). Anti-inflammatory activity.

RIPK1-IN-12 is a potent RIPK1 inhibitor. RIPK1-IN-12 inhibits necroptosis in both human and mouse cells, with EC50 values of 1.6 and 2.9 nM, respectively.