Bcl-2 Family Inhibitor

Gambogic Acid (Beta-Guttiferrin) is derived from the gamboges resin of the tree Garcinia hanburyi. Gambogic Acid (Beta-Guttiferrin) inhibits Bcl-X_L, Bcl-2, Bcl-W, Bcl-B, Bfl-1 and Mcl-1 with IC₅₀s of 1.47 μM, 1.21 μM, 2.02 μM, 0.66 μM, 1.06 μM and 0.79 μM.

BI-3802, a chemical probe, is a highly potent BCL6 degrader and inhibits the Bric-à-brac (BTB) domain of BCL6 with an IC₅₀ of ≤3 nM. BI-3802 induces the polymerization of BCL6 and promotes BCL6 degration depended on E3 ligase SIAH1. BI-3802 has antitumor activity.

D-​(+)​-​Phenyllactic acid is an anti-bacterial agent, excreted by Geotrichum candidum, inhibits a range of Gram-positive from humans and foodstuffs and Gram-negative bacteria found in humans.

Chelerythrine chloride is a potent, cell-permeable inhibitor of protein kinase C, with an IC₅₀ of 660 nM. Chelerythrine chloride inhibits the Bcl-XL-Bak BH3 peptide binding with IC₅₀ of 1.5 μM and displaces Bax from Bcl-XL. Chelerythrine chloride induces apoptosis and autophagy.

Obatoclax Mesylate (GX15-070 Mesylate), a BH3 mimetic, is a pan-BCL-2 family proteins inhibitor with a K_i of 220 nM for BCL-2. Obatoclax Mesylate induces autophagy-dependent cell death and targets cyclin D1 for proteasomal degradation. Obatoclax Mesylate has anti-cancer and broad-spectrum antiparasitic activity.

Bax inhibitor peptide V5 (BIP-V5) is a Bax-mediated apoptosis inhibitor, used for cancer treatment.

Sorafenib-d₃ (Donafenib) is the deuterated-labeled Sorafenib (HY-10201). Sorafenib (Bay 43-9006) is a potent oral active multikinase inhibitor. Sorafenib blocks autophosphorylation and activity of receptor tyrosine kinases (VEGFR-2, VEGFR-3) and RAF family kinases, thereby suppressing the RAF/MEK/ERK and PI3K/Akt pathways, inhibiting STAT3 phosphorylation, and selectively inhibiting the MAPK pathway in cancer cells. Sorafenib induces cell cycle arrest, autophagy, apoptosis, and PARP cleavage, reduces Bcl-2, Bcl-XL, cyclin D1 levels, and activates Bak and Bax. Sorafenib inhibits tumor growth and metastasis in mouse and rat models. Sorafenib can be used for cancer research, such as colon, breast, non-small-cell lung cancer (NSCLC), ovarian, pancreatic, melanoma, colorectal and hepatocellular carcinoma.

MRT68921 dihydrochloride is a potent NUAK1/ULK1 dual inhibitor. MRT68921 dihydrochloride inhibits ULK1 and ULK2 with IC₅₀ values of 2.9 nM and 1.1 nM, respectively. MRT68921 dihydrochloride can block cells autophagy and kill tumor cells by breaking the balance of oxidative stress signals. MRT68921 dihydrochloride can inhibit cell proliferation and induce ROS production and apoptosis. MRT68921 dihydrochloride can be used for the research of cancer, such as breast cancer.

Levonorgestrel is an orally active inhibitor of progesterone (HY-N0437). Levonorgestrel has anticancer activity and can induce Apoptosis. Levonorgestrel can be used as a contraceptive and in combination with other medications. Levonorgestrel can be used in the study of osteoporosis and uterine leiomyoma.

UMI-77 is a selective Mcl-1 inhibitor, which shows high binding affinity to Mcl-1 (IC₅₀=0.31 μM). UMI-77 binds to the BH3 binding groove of Mcl-1 with K_i of 490 nM, showing selectivity over other members of anti-apoptotic Bcl-2 members.

AZD4320 is a novel BH3-mimicking dual BCL2/BCLxL inhibitor with IC₅₀s of 26 nM, 17 nM, and 170 nM for KPUM-MS3, KPUM-UH1, and STR-428 cells, respectively.

TCPOBOP is a constitutive androstane receptor (CAR) agonist that induces robust hepatocyte proliferation and hepatomegaly without any liver injury or tissue loss. TCPOBOP attenuates Fas-induced murine liver injury by altering Bcl-2 proteins.

Daphnetin (7,8-dihydroxycoumarin), one coumarin derivative can be found in plants of the Genus Daphne, is a potent, oral active protein kinase inhibitor, with IC₅₀s of 7.67 μM, 9.33 μM and 25.01 μM for EGFR, PKA and PKC in vitro, respectively. Daphnetin triggers ROS-induced cell apoptosis and induces cytoprotective autophagy by modulating the AMPK/Akt/mTOR pathway. Daphnetin has anti-inflammation activitity and inhibits TNF-α, IL-1β, ROS, and MDA production. Daphnetin has schizontocidal activity against malaria parasites. Daphnetin can be used for rheumatoid arthritis , cancer and anti-malarian research.

Cardamonin can be found from cardamom, and can target various signaling molecules, transcriptional factors, cytokines and enzymes. Cardamonin can inhibit mTOR, NF-κB, Akt, STAT3, Wnt/β-catenin and COX-2. Cardamonin shows anticancer, anti-inflammatory, antimicrobial and antidiabetic activities.

Azoramide is a potent, orally active small-molecule modulator of the unfolded protein response (UPR). Azoramide improves ER protein folding and elevates ER chaperone capacity, which together protects cells against ER stress. Azoramide alleviates PLA2G6 mutant-induced ER stress through modulating unfolded protein response, and enhances the CERB signaling to rescue mitochondrial function, thereby preventing apoptosis of DA neurons. Azoramide has antidiabetic activity.

AS 1411 (AGRO-100) is an oligonucleotide aptamer targeting nucleoproteins. AS 1411 inhibits tumor cell proliferation by affecting the activity of nucleoprotein-containing complexes and can be used as a carrier to precisely deliver nanoparticles, oligonucleotides and small molecules to cancer cells. AS 1411 reduces PRMT5 expression to inhibit tumor growth in DU145 prostate cancer cells. AS 1411 works by blocking the binding of nucleoproteins to bcl-2 mRNA in MCF-7 breast cancer cells. AS 1411-coupled Jin nanospheres can inhibit breast cancer cell proliferation in vitro and in mouse models, has the ability to cross the blood-brain barrier with low tissue toxicity.

Lisaftoclax is an orally active, selective BCL-2 inhibitor with a K_i of < 0.1 nM against human BCL-2. Lisaftoclax selectively binds to BCL-2, disrupts the BCL-2:BIM complex, and antagonizes the antiapoptotic function of BCL-2. Lisaftoclax induces BAX/BAK-dependent, caspase-mediated apoptosis, upregulates the pro-death proteins BIM and Noxa, and downregulates mitochondrial respiratory function and ATP production. Lisaftoclax can be used in the research of hematological malignancies including chronic lymphocytic leukemia, multiple myeloma, and diffuse large B-cell lymphoma.

Azadirachtin is an oral active triterpenoid compound with anticancer, antimalarial, anti-inflammatory, and insecticidal activities. Azadirachtin induces cell apoptosis through the mitochondrial pathway (by inhibiting Bcl-2/Bax ratio or activating Apaf-1 and caspase-3) or through death receptors (by inhibiting TNFR activation). Additionally, Azadirachtin exerts its anti-inflammatory effects by inhibiting NF-кB signaling pathway activation, and it exhibits insecticidal activity by inducing apoptosis in insect cells.

MSN-125 is a potent Bax and Bak oligomerization inhibitor. MSN-125 prevents mitochondrial outer membrane permeabilization (MOMP) with an IC₅₀ of 4 μM. MSN-125 potently inhibits Bax/Bak-mediated apoptosis in HCT-116, BMK Cells, and primary cortical neurons, protects primary neurons against glutamate excitotoxicity.

ABBV-467 is a selective MCL-1 inhibitor (K_i: <0.01 nM). ABBV-467 induces apoptosis. ABBV-467 induces cancer cell death and inhibits tumor growth in models of hematological malignancies, such as multiple myeloma.