IAP Inhibitor

LCL161 is a IAP inhibitor which inhibits XIAP in HEK293 cell and cIAP1 in MDA-MB-231 cell with IC₅₀s of 35 and 0.4 nM, respectively.

Anticancer agent 294 (Example 2) is an anticancer agent that has inhibitory activity against apoptosis inhibitor protein 1 (cIAP1) with an IC₅₀ of 15 nM.

FL118 (10,11-(Methylenedioxy)-20(S)-camptothecin), a Camptothecin (HY-16560) analogue, is a potent and orally active survivin inhibitor. FL118 binds to oncoprotein DDX5 (p68) to dephosphorylates and degrades DDX5. FL118 can be used for the research of cancer.

GDC-0152 is a potent IAPs inhibitor, and binds to the BIR3 domains of XIAP, cIAP1, cIAP2 and the BIR domain of ML-IAP with K_i values of 28 nM, 17 nM, 43 nM and 14 nM, respectively.

Jolkinolide B is a bioactive diterpene isolated from the roots of Euphorbia fischeriana Steud with oral activity. Jolkinolide B downregulates XIAP, cIAP1, cIAP2, and phosphorylated Akt, upregulates Smac, activates caspase-3 and caspase-9, and inhibits NF-κB, TGFβ/smad3 and JAK/STAT3 pathways. Jolkinolide B exerts comprehensive biological effects including inducing cancer cell apoptosis, suppressing inflammatory responses, improving lung function, alleviating hepatic steatosis and eliminating intracellular Mycobacterium tuberculosis. Jolkinolide B can be used for the research of leukemia, histiocytic lymphoma, asthma, metabolic dysfunction-associated steatotic liver disease and tuberculosis.

MX69 is an inhibitor of MDM2/XIAP, used for cancer treatment.

CUDC-427 is a potent second-generation pan-selective IAP antagonist, used for treatment of various cancers.

XIAP degrader-1, a primary amine tethered small molecule, promotes the degradation of X-linked inhibitor of apoptosis protein (XIAP).

Flavokawain A is a chalcone compound and an orally active inhibitor of PRMT5 and cytochrome P450. Flavokawain A has anti-inflammatory, anti-tumor, and immunomodulatory effects. Flavokawain A can inhibit the proliferation of tumor cells and induce apoptosis. Flavokawain A can be used in the research of diseases such as bladder cancer.

1-Monopalmitin (Glyceryl palmitate) is an activator of the PI3K/Akt pathway and an inhibitor of P-glycoprotein (P-gp). 1-Monopalmitin can induce G2/M arrest and caspase-dependent apoptosis in cancer cells, while inhibiting IAPs protein expression. 1-Monopalmitin can increase drug accumulation by inhibiting P-gp activity in intestinal Caco-2 cells. 1-Monopalmitin has the ability to induce protective autophagy and apoptosis of lung cancer cells (IC₅₀=50-58 μg/mL), with low toxicity to normal cells.

Flavokawain C is an orally active natural chalcone. Flavokawain C inhibits the proliferation of various cancer cells. Flavokawain C upregulates GADD153 in cancer cells, inhibits the phosphorylation of Akt and JNK, suppresses early ERK phosphorylation, activates late ERK phosphorylation, activates caspase related subtypes, induces PARP-1 cleavage, causes upregulation of p21 and p27, downregulation of mutant p53 and anti-apoptotic IAP proteins, elevates intracellular ROS levels, reduces SOD activity, and induces apoptosis. Flavokawain C downregulates FABP4, induces autophagy in cancer cells, and activates the AMPK/mTOR pathway. Flavokawain C decreases the expression of glycolysis-related proteins GLUT1 and HK2, and inhibits glycolysis in nasopharyngeal carcinoma cells. Flavokawain C inhibits the activation of the EGFR/PI3K/Akt/mTOR signaling pathway and reduces the expression of HSP90B1. Flavokawain C inhibits angiogenesis by decreasing the expression of angiogenic proteins Ang-1 and VEGF in human umbilical vein endothelial cells. Flavokawain C increases γ-H2AX levels in cells, inhibits the phosphorylation of FAK, PI3K and AKT in cells, and induces DNA damage in cells. Flavokawain C exerts anti-tumor activity in multiple tumor xenograft mouse models. Flavokawain C is applicable to research related to colorectal cancer, colon adenocarcinoma, nephroblastoma, nasopharyngeal carcinoma and liver cancer.

Polygalacin D (PGD) is a bioactive compound isolated from Platycodon grandiflorum with anticancer and anti-proliferative properties. PGD suppresses the expression of the IAP family of proteins including survivin, cIAP-1 and cIAP-2 and blocks the PI3K/Akt pathway by inhibiting the phosphorylation of GSK3β, Akt and the expression of PI3K. Polygalacin D induces apoptosis

A 410099.1 is a BIRC inhibitor, with EC₅₀ values for BIRC2, BIRC3, BIRC4, BIRC7, and BIRC8 are 4.6, 9.2, 15.6, 19.9, and 93.9 nM, respectively.

Hellebrigenin is an inhibitor that selectively targets the MAPK signaling pathway (ERK, p38, JNK) and XIAP, and can inhibit Akt expression and phosphorylation. Hellebrigenin can activate endogenous apoptosis pathways (such as mitochondrial membrane potential disruption, Caspase family activation, PARP cleavage), downregulate anti-apoptotic proteins (Bcl-2, Bcl-xL) and upregulate pro-apoptotic proteins (Bax, Bak). Hellebrigenin can also induce DNA double-strand breaks to activate the ATM pathway. Hellebrigenin can inhibit tumor cell proliferation and clone formation, and is mainly used in the study of oral squamous cell carcinoma, liver cancer and other cancers.

PBX-7016 is a Camptothecin (HY-16560) derivative. PBX-7016 can selectively inhibit Topoisomerase 1. PBX-7016 can specifically bind and degrade the cancer protein DDX5, thereby down-regulating the expression of anti-apoptotic proteins such as Survivin, Mcl-1, and XIAP, and promoting the apoptosis of cancer cells. PBX-7016 can be used to synthesis of ADCs.

Isolinderalactone is a sesquiterpene that exhibits anti-cancer, anti-inflammatory, and neuroprotective effects. Isolinderalactone inhibits VEGF expression and tyrosine phosphorylation of VEGFR2. Isolinderalactone decreases viability and induces apoptosis in U-87 glioblastoma (GBM) cells and colorectal cancer (CRC) cells. Isolinderalactone induces G2/M phase cell cycle arrest, ROS generation, pJNK/p38 MAPK activation, in colorectal cancer (CRC) cells. Isolinderalactone blocks LPS (HY-D1056)-induced NF-κB activation while activating Nrf2-HMOX1 signaling in RAW264.7 macrophages. Isolinderalactone improves cognitive dysfunction in APP/PS1 mice. Isolinderalactone can be used for the study of Glioblastoma multiforme (GBM), colorectal cancer, Alzheimer’s disease and acute lung injury.

UC-112 is a XIAP inhibitor with anticancer activity. UC-112 selectively downregulates and degrades survivin via the ubiquitin-mediated proteasomal degradation pathway. UC-112 reduces XIAP levels in in vivo tumor models. UC-112 activates caspase-3/7 and caspase-9, and induces cancer cell apoptosis. UC-112 is applicable to studies on melanoma, prostate cancer and cancer-related research.

SM-433, a Smac mimetic, function as inhibitor of inhibitor of apoptosis proteins (IAPs). SM-433 exhibits strong binding affinity XIAP BIR3 protein with an IC₅₀<1 μM (patent WO2008128171A2).

Sanggenon G is a cell-permeable and potent inhibitor of X-linked inhibitor of apoptosis protein (XIAP). Sanggenon G binds specifically to the BIR3 domain of XIAP with a binding affinity of 34.26 μM. Sanggenon G enhances caspase activation.

SM-433 hydrochlorid, a Smac mimetic, function as inhibitor of inhibitor of apoptosis proteins (IAPs). SM-433 hydrochlorid exhibits strong binding affinity XIAP BIR3 protein with an IC₅₀<1 μM (patent WO2008128171A2).