bcl-2-in-2

Bcl-2-IN-2 is a highly potent and selective inhibitor targeting Bcl-2 and Bcl-xL, displaying an IC50 value of 0.034 nM against Bcl-2 and 43 nM against Bcl-xL, demonstrating over 1000-fold selectivity for Bcl-2 compared to Bcl-xL.

MCL-1/BCL-2-IN-2 is a potent and selective dual inhibitor of Bcl-2 and Mcl-1.

Bcl-2-IN-22 (compound 1), a gold (I) NHC complex, exhibits anticancer activity. It induces cell death (apoptosis) via the mitochondrial pathway with an IC50 value of 0.014 μM. Additionally, Bcl-2-IN-22 targets members of the BCL-2 family, promoting apoptosis and sensitization in multidrug-resistant leukemia cells overexpressing BCL-2.

Bcl-2-IN-20 (Compound 81) is a Bcl-2 inhibitor with an IC50 of less than 10 μM, achieving a 79.1% inhibition rate at 9 μM. It demonstrates cytotoxicity in cell lines such as SK-MEL-28 (IC50 > 10 μM), A549 (IC50 = 6.1 μM), HepG2 (IC50 > 10 μM), MCF-7 (IC50 = 8.9 μM), HCT116 (IC50 > 10 μM), and HEK-293 (IC50 = 14.1 μM). Bcl-2-IN-20 also promotes the generation of ROS, inducing apoptosis and DNA damage.

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.

Bcl-2-IN-21 (compound C1), an iridium-based anticancer agent, effectively targets and inhibits Bcl-2, thereby impeding cancer cell colony formation and promoting increased levels of Bax and caspase 3.

Polyphyllin D induces apoptosis via the mitochondrial apoptotic pathway as evidenced by decreased Bcl-2 expression levels, disruption of MMP and increased Bax, cytochrome C, and cleaved-caspase-3 levels. Polyphyllin D has an anti-angiogenic effect. Polyphyllin D has toxicity in human RBCs as well as its underlying mechanism for the hemolysis and eryptosis/erythroptosis. Polyphyllin D has strong anticancer activity, can overcome drug resistance in R-HepG2 cells and elicit programmed cell death via mitochondrial dysfunction.

1. Dehydrocorydaline (13-Methylpalmatine) exerts anti-metastatic potential via suppression of MMPs and Bcl-2 signaling in NSC-LC cells. 2. Dehydrocorydaline stimulates p38 MAPK activation, which can enhance heterodimerization of MyoD and E proteins, thus resulting in MyoD activation and myoblast differentiation. 3. Dehydrocorydaline shows antiplatelet effects, it inhibits thrombin-induced platelet aggregation in a low dose ( IC50= 34.914 ug/mL). 4. Dehydrocorydaline has anti-inflammatory and antinociceptive effects. 5. Dehydrocorydaline inhibits MCF-7 cell proliferation by inducing apoptosis mediated by regulating Bax/Bcl-2, activating caspases as well as cleaving PARP.

Bcl-xL antagonist 2 is an effective and selective antagonist of Bcl-xL with an IC50 of 91 nM and a Ki of 65 nM. Bcl-xL antagonist 2 induces apoptosis in cancer cells and can be used in studies about chronic lymphocytic leukemia and non-Hodgkin's lymphoma.

TV 3279 is a novel ChE-MAI inhibitor , and the neuroprotective properties depend on their ability to induce the anti-apoptotic proteins PKC, Bcl-2, Bcl-x, and SOD, and to block the nuclear translocation of the pro-apoptotic enzyme glyceraldehyde phosphate dehydrogenase in PC-12 and neuroblastoma cells.

Docetaxel trihydrate (RP-56976 Trihydrate) is an antineoplastic agent that has a unique mechanism of action as an inhibitor of cellular mitosis and that currently plays a central role in the therapy of many solid tumor including breast and lung cancer. Therapy with docetaxel has been associated with a low rate of serum enzyme elevations and rarely to instances of acute hepatic necrosis generally due to severe hypersensitivity reactions or sepsis.

Amygdalin (Laetrile) has antifibrotic, antitumor, anti-inflammatory and analgesic effects, amygdalin joint HSYA could inhibit the degeneration of the endplate chondrocytes derived from intervertebral discs of rats induced by IL-1beta and better than the single use of Amygdalin or HSYA. Amygdalin induces apoptotic cell death in human DU145 and LNCaP prostate cancer cells by caspase-3 activation through down-regulation of Bcl-2 and up-regulation of Bax.

Vanillyl Alcohol (3-Methoxy-4-hydroxybenzyl alcohol) possesses anti-angiogenic, anticonvulsive, anti-inflammatory, anti-oxidant, neuroprotective, and anti-nociceptive activities. Vanillyl alcohol can effectively inhibit the cytotoxicity and improved cell viability in 1-methyl-4-phenylpyridinium (MPP+)-induced MN9D dopaminergic cells, it also can attenuate the elevation of reactive oxygen species (ROS) levels, decrease in the Bax/Bcl-2 ratio and poly (ADP-ribose) polymerase proteolysis.

Ethyl gallate (gallic acid ethyl ester) obviously decreases cell proliferation in MDA-MB-231 and MCF-7 cells in a dose- and time-dependent manner, exhibits cytotoxicity in a dose-dependent manner. Ethyl gallate can inhibit the abilities of invasion of breast cancer in vitro by inhibiting the mRNA levels of MMP-9/MMP-2, phosphorylation of Akt and protein expression of NF-κB and inhibits hydrogen peroxide signaling, may represent an alternative class of vasopressors for use in septic shock. Also, Ethyl gallate suppresses proliferation and invasion in human breast cancer cells by modulating the PI3K/Akt pathway, which may contribute to inhibiting their downstream targets such as NF-κB p-65, Bcl-2/Bax, and mRNA levels of MMP-2 and MMP-9 in breast cancer cells, could be used as potential antioxidants with safe therapeutic application in cancer chemotherapy.

TS-0022666 is a selective TUT4/7 inhibitor exhibiting antiproliferative and anti-leukaemic activity in vivo and in vitro. It enhances THP-1 cell sensitivity to BCL-2 inhibition, reduces uridylation, and may be used to study cancers with FOCAD deficiency.

Rubone (2'-Hydroxy-2,4,4',5,6'-pentamethoxychalcone), a natural product and a modulator of miR-34a (microRNA-34), upregulates miR-34a expression in a p53-dependent manner, which in turn downregulates the expression of downstream targets Bcl-2, cyclin-D1, CDK6, SIRT1, and FOXP1, thereby inhibiting tumor growth and reversal of hepatocellular carcinoma (HCC) and chemoresistance in prostate cancer.

D-Isofloridoside, a polysaccharide precursor, exhibits free radical scavenging activity and inhibits both ROS expression and the enzymes MMP-2 and MMP-9.

Chlorahololide D is a natural lindane-type sesquiterpene dimer and selective potassium channel blocker that stimulates reactive oxygen species ROS levels to cause cell cycle arrest in the G2 phase, modulates Bcl-2 and Bax and FAK, thereby inhibiting MCF-7 cell growth and triggering apoptosis. Chlorahololide D inhibits tumor proliferation, migration and angiogenesis in in vivo experiments and has anti-breast cancer potential.

A-1211212 (BCL2-IN-1) is a potent and selective Bcl-2 inhibitor. It promotes lymphocyte apoptosis, alters colonic mucosa in mice, and improves inflammation.

Nitroaspirin (NCX 4016) is a nitric oxide donor and a nitro-derivative of Aspirin that inhibits cyclooxygenase. It induces cell cycle arrest and apoptosis in Cisplatin-resistant human ovarian cancer cells by down-regulating EGFR/PI3K/STAT3 signaling and modulating Bcl-2 family proteins. Additionally, Nitroaspirin possesses antithrombotic and antiplatelet properties and acts as a direct and irreversible inhibitor of COX-1.

Destruxin B is a cyclic peptide with insecticidal and anticancer activity isolated from the insect pathogenic fungus Metarhizium isopliae. Destruxin B induces apoptosis of human non-small cell lung cancer cells through the Bcl-2 family-dependent mitochond

MCL-1/BCL-2-IN-2 (Compound Nap-1) is a potent and selective dual inhibitor of Mcl-1 and Bcl-2, with IC50 values of 4.45 μM and 3.18 μM, respectively [1].

MCL-1/BCL-2-IN-3 is a selective and potent dual inhibitor of Mcl-1 and Bcl-2, with IC50 values of 5.95 and 4.78 μM, respectively.

MCL-1/BCL-2-IN-4 is a selective and potent dual inhibitor of Mcl-1 and Bcl-2.