Bcl-2 Family

Navitoclax (ABT-263) is a potent oral Bcl-2 inhibitor that binds to Bcl-xL, Bcl-2, and Bcl-w proteins (Ki<1 nM), demonstrating antitumor activity and inducing apoptosis.

Venetoclax (ABT-199) is a Bcl-2 inhibitor (Ki<0.01 nM) with potent, selective, and orally active properties. Venetoclax has a 3-order-of-magnitude lower affinity for Bcl-xL and Bcl-W (Kis=48 245 nM). Venetoclax induces autophagy and apoptosis.

S63845 is a selective myeloid leukemia 1(MCL1) inhibitor that binds to human MCL1 with a Kd of 0.19 nM.

ABT-737 is a BH3 mimetic and an inhibitor of Bcl-2, Bcl-xL, and Bcl-w (EC50=30.3 nM 78.7 nM 197.8 nM). ABT-737 exhibits antitumor activity and anti-aging activity.

MIK665 (S-64315) (S-64315) has an inhibitory effect on myeloid leukemia.

N-Methylnicotinamide is one of the endogenous metabolites that ameliorates endothelial dysfunction.

BT2, a BCKDC kinase (BDK) inhibitor, exhibits an IC50 of 3.19 μM and functions as a potent, selective Mcl-1 inhibitor with a Ki value of 59 μM. Its interaction with BDK induces helix movements in the N-terminal domain, leading to BDK's dissociation from the branched-chain α-ketoacid dehydrogenase complex (BCKDC).

Kurarinone is a flavonoid extracted from the shrub Sophora flavescens, which has anti-tumor, estrogenic and anti-inflammatory activities, and also has a strong inhibitory effect on immune responses.

Se-Methylselenocysteine (Se-MSC) is a potent chemopreventive agent in many test systems and has been shown to inhibit tumor promotion and induce apoptosis.

Obatoclax Mesylate (GX15-070) is a Bcl-2 antagonist (Ki: 0.22 μM) and can induce apoptosis with up-regulation of Bim, induced cytochrome c release, and activation of caspase-3.

Gambogic Acid (Guttic Acid) ( EC50=0.78-1.64 uM) activates caspases. Gambogic Acid competitively suppresses Bcl-XL, Bcl-2, Bcl-W, Bcl-B, Bfl-1 and Mcl-1. The IC50s of Gambogic Acid for Bcl-XL, Bcl-2, Bcl-W, Bcl-B, Bfl-1 and Mcl-1 are 1.47, 1.21, 2.02, 0.66, 1.06 and 0.79 uM, respectively.

Erianin is a nature product extracted from Dendrobium chrysotoxum, has notable antitumour activity , can cause extensive tumour necrosis, growth delay. Erianin has antiangiogenic action by inhibiting endothelial metabolism in a JNK SAPK-dependent manner a

Jaceosidin has anti-oxidative activity. Jaceosidin has anti-inflammatory activity, also a microglial inhibitor with anti-neuroinflammation activity. aceosidin has anticancer activity, modulates the ERK ATM Chk1 2 pathway, leading to inactivation of the Cd

Navitoclax-piperazine (ABT-263-piperazine) is a B-cell lymphoma extra large (BCL-XL) inhibitor.

PF-07328948 is a branched-chain keto acid dehydrogenase kinase (BDK) inhibitor, useful in research on cardiovascular disease (CVD) and metabolic disorders.

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

A-1331852 is a potent and selectiveBCL-XL inhibitor and may be useful in the treatment of cancer, immune and autoimmune diseases.

Jolkinolide B is a bioactive diterpene isolated from the roots of Euphorbia fischeriana Steud. Jolkinolide B induces apoptosis in cancer cells. Jolkinolide B can be used for studies on preventing and treating osteolysis.

S55746 (BLC201) is an effective and selective BCL-2 inhibitor (Ki: 1.3 nM and a Kd of 3.9 nM).

UMI-77 is a selective Mcl-1 inhibitor. UMI-77 binds to the BH3-binding groove of Mcl-1 with a Ki of 490 nM and is selective over other members of the Bcl-2 family.

BAI1 (Bax channel blocker) is a potent inhibitor of Bax-mediated mitochondrial cytochrome C release (IC50: 0.52 μM).

Lisaftoclax (Bcl-2 Bcl-xl inhibitor 1) is an oral dual inhibitor of Bcl-2 and Bcl-xl, with IC50 values of 2 nM and 5.9 nM for Bcl-2 and Bcl-xl, respectively. Lisaftoclax is used to treat chronic lymphocytic leukemia (CLL) by inhibiting the action of the BCL-2 protein, which promotes the death of leukemia cells.

Dihydrokaempferol (Aromadendrin) is a natural product. It induces apoptosis and inhibits Bcl-2 and Bcl-xL expression, possesses anti-inflammatory, antioxidant, and anti-diabetic properties, it exhibits anti-inflammatory activity

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.

1. Chelerythrine (Broussonpapyrine) may have antimanic effect . 2. Chelerythrine can inhibit telomerase activity. 3. Chelerythrine is a well-known protein kinase C inhibitor . 4. Chelerythrine has potential antiproliferative and antitumor effects.

Chelerythrine Chloride is a cell-permeable inhibitor of protein kinase C, competitive with respect to the phosphate acceptor and non-competitive with respect to ATP.

BI-3802, a highly potent BCL6 degrader, targets and inhibits the Bric-à-brac (BTB) domain of BCL6, exhibiting an IC50 value of ≤3 nM. It induces polymerization of BCL6 and facilitates its degradation in a manner dependent on the E3 ligase SIAH1, demonstrating notable antitumor activity[1][2].

ARV-393 HCl is an orally active and potent PROTAC targeting BCL6 with antitumor activity for the study of non-Hodgkin's lymphoma.

Paris saponin VII (Dioscini) shows inhibitory effects on cell proliferation.

3',6-Disinapoylsucrose (Disinapoyl sucrose) shows the neuroprotective effect and antidepressive activity in rats.

AZD4320 is an inhibitor of BH3-mimicking dual BCL2 BCLxL. For KPUM-MS3, KPUM-UH1, and STR-428 cells, the IC50s values are 26 nM, 17 nM, and 170 nM , respectively.

Clitocine, an adenosine analogue derived from mushrooms, is a potent transcriptional readout agent, an inhibitor of nonsense mutations, and has anticancer activity, inducing the production of p53 protein in cells carrying the p53 nonsense mutation allele.Clitocine enhances TRAIL-mediated apoptosis in human colon cancer cells by promoting Mcl-1 degradation.NSC 81464 is an alkaloid of the yohimbine type extracted from the roots and leaves of Rauwolfia vomitoria.

BTSA1 is a BAX activator that binds with high affinity and specificity to the N-terminal activation site and induces conformational changes to BAX leading to BAX-mediated apoptosis.

BCL6-IN-3 is a potent BCL6 inhibitor with GI50 of 70 nM in SU-DHL4 cells. BCL6-in-3 regulates cell activation, differentiation, DNA damage and apoptosis, and has antitumor activity.

A-385358 is a selective Bcl-xL inhibitor with Kis of 0.80 nM for Bcl-xL and 67 nM for Bcl-2, respectively.

Moringin is an isothiocyanate obtained from myrosinase-mediated hydrolysis of the glucosinolate precursor glucoMoringin present in Moringa oleifera seeds. Moringin has anti-inflammatory and antioxidative properties.

Tapotoclax (AMG-176) is an orally active MCL1 inhibitor for the study of myeloid leukemia.

ML311 is a selective inhibitor of the Mcl-1 Bim interaction.

Gossypol (BL 193) Acetate is a polyphenolic aldehyde that permeates cells and acts as an inhibitor for several dehydrogenase enzymes.

Myristicin (Myristicine) is a natural product found in spices and umbelliferous plants. Myristicin has anti-cholinergic, Antibacterial, and hepatoprotective effects, it also has anti-inflammatory properties related with its inhibition of NO, cytokines,chemokines, and growth factors in dsRNA-stimulated macrophages via the calcium pathway. Myristicin can induce Apoptosis as characterised by alterations in the mitochondrial membrane potential, cytochrome c release, Caspase-3 activation, PARP-cleavage and DNA fragmentation.

IMB-XH1 (Mcl1-IN-2) is a myeloid cell factor 1 (Mcl-1) inhibitor.

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.

Paederosidic acid has significant anti-tumor, anticonvulsant and sedative effects. Paederosidic acid increases brain gamma-aminobutyric acid and decreases glutamic acid in the brain, and it up-regulates expressions of GAD 65, may be a promising future the

Hinokiflavone, a novel modulator of pre-mRNA splicing activity both in vitro and in cellulo, inhibits the assembly of the spliceosome, particularly blocking the formation of the B complex. Additionally, it acts as a SUMO protease inhibitor by impeding the activity of sentrin-specific protease 1 (SENP1). Hinokiflavone also demonstrates significant cytotoxicity, including the inhibition of MMP-9.

δ-Tocotrienol (Delta-Tocotrienol) is a potential angiogenic inhibitor. δ-Tocotrienol is also a nontoxic activator of mir-34a which can inhibit nonsmall cell lung cancer cells (NSC-LC) cell proliferation, induce apoptosis and inhibit invasion, and thus offering a potential starting point for the design of novel anticancer agents.

Sabutoclax (BI-97C1)(BI-97C1) is a pan-Bcl-2 inhibitor, including Bcl-xL, Bcl-2, Mcl-1 and Bfl-1 with IC50 of 0.31 μM, 0.32 μM, 0.20 μM and 0.62 μM, respectively.

Orobol (3',4',5,7-tetrahydroxy-isoflavon) is an inhibitor of tyrosine-specific protein kinase and phosphatidylinositol turnover. Orobol inhibits PI3K isoforms with IC50s of 3.46-5.27 μM for PI3K α β γ K δ. Orobol exhibits anti-skin-aging and anti-obesity effects.

A09-003 is a novel cell cycle protein-dependent kinase-9 CDK-9 inhibitor.A09-003 inhibits the proliferation of a variety of leukemia cell lines and inhibits the increase of leukemia sequence-1 protein in myeloid cells.A09-003 also induces apoptosis, decreases RNA polymerase II activity, and decreases Mcl-1 expression.