Mcl-1 Inhibitor

S63845 is a potent and selective myeloid cell leukemia 1 (MCL1) inhibitor with a K_d of 0.19 nM for human MCL1.

ABT-737, a BH3 mimetic, is a potent Bcl-2, Bcl-x_L and Bcl-w inhibitor with EC₅₀s of 30.3 nM, 78.7 nM, and 197.8 nM, respectively. ABT-737 induces the disruption of the BCL-2/BAX complex and BAK-dependent but BIM-independent activation of the intrinsic apoptotic pathway. ABT-737 induces autophagy and has the potential for acute myeloid leukemia (AML) research.

A-1331852 is an orally available BCL-XL selective inhibitor with a K_i of less than 10 pM.

BT2 is a BCKDC kinase (BDK) inhibitor with an IC₅₀ of 3.19 μM. BT2 binding to BDK triggers helix movements in the N-terminal domain, resulting in the dissociation of BDK from the branched-chain α-ketoacid dehydrogenase complex (BCKDC). BT2 (compound 4) is also a potent and selective Mcl-1 inhibitor with a K_i value of 59 μM.

AZD-5991 is a potent and selective Mcl-1 inhibitor with an IC₅₀ of 0.7 nM in FRET assay and a K_d of 0.17 nM in surface plasmon resonance (SPR) assay.

Bcl-2/Mcl-1-IN-5 (Compound S6) is a Bcl-2 and Mcl-1 inhibitor. Bcl-2/Mcl-1-IN-5 promotes Apoptosis, downregulates anti-apoptotic proteins Bcl-2 and Mcl-1, induces mitochondrial membrane potential depolarization, and activates the Caspase-dependent apoptotic cascade, as evidenced by Caspase-3 activation and PARP1 cleavage. Bcl-2/Mcl-1-IN-5 has anti-hepatocellular carcinoma activity.

Mcl-1-IN-22 is a selective Mcl-1 inhibitor with a K_i of 0.015 μM. Mcl-1-IN-22 binds selectively to Mcl-1, disrupts the Mcl-1/Bak complex to release free Bak, triggering intrinsic apoptosis. Mcl-1-IN-22 can be used for the research of ovarian cancer.

MIK665 (S-64315), derived from S63845, is a myeloid cell leukemia sequence 1 (MCL1) inhibitor. MIK665 has an IC₅₀ of 1.81 nM for MCL1.

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.

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.

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.

A-1210477 is a potent and selective inhibitor of MCL-1 with a K_i of 0.45 nM. A-1210477 specifically binds MCL-1 and promotes apoptosis of cancer cells in an MCL-1-dependent manner.

PROTAC Bcl2 degrader-1 (Compound C5) is a PROTAC based on Cereblon ligand, which potently and selectively induces the degradation of Bcl-2 (IC₅₀, 4.94 μM; DC₅₀, 3.0 μM) and Mcl-1 (IC₅₀, 11.81 μM) by introducing the E3 ligase cereblon (CRBN)-binding ligand pomalidomide to Mcl-1/Bcl-2 dual inhibitor Nap-1.

PROTAC Mcl1 degrader-1 (compound C3), a proteolysis targeting chimera (PROTAC) based on Cereblon ligand, is a potently and selectively Mcl-1 (Bcl-2 family member) inhibitor with an IC₅₀ of 0.78 μM. PROTAC Mcl1 degrader-1 inhibits Bcl-2 with an IC₅₀ of 0.54 μM.

TW-37 is a potent Bcl-2 inhibitor with K_i values of 260, 290 and 1110 nM for Mcl-1, Bcl-2 and Bcl-xL, respectively.

(R)-(-)-Gossypol (AT-101) is the levorotatory isomer of a natural product Gossypol. AT-101 is determined to bind to Bcl-2, Mcl-1 and Bcl-xL proteins with K_is of 260±30 nM, 170±10 nM, and 480±40 nM, respectively.

Tapotoclax (AMG-176) is a potent, selective and orally active MCL-1 inhibitor, with a K_i of 0.13 nM.

SHP2-D26 is a SHP2 PROTAC degrader with DC₅₀ values of 6.0 nM (KYSE520 cells) and 2.6 nM (MV4;11 cells), respectively. SHP2-D26 inhibits ERK phosphorylation, upregulates Bim levels, downregulates Mcl-1 levels, and induces cell cycle arrest and apoptosis. SHP2-D26 can be used in studies related to esophageal cancer, acute myeloid leukemia and non-small cell lung cancer.

TC11 is a MCL1 degrader and Caspase-9 and CDK1 activator. TC11 functions as a phenylacetylamide derivative and is structurally related to immunomodulatory active molecules. TC11 induces degradation of MCL1 leading to apoptotic death during prolonged mitotic arrest.

Sabutoclax is a potent and effective Bcl-2 Family (Bcl-2, Bcl-XL, Mcl-1, Bfl-1) inhibitor with IC₅₀s of 0.32 μM, 0.31 μM, 0.20 μM, and 0.62 μM, respectively. Sabutoclax increases Bax, Bim, PUMA and survivin expression.