Bcl-xL Inhibitor

Venetoclax (ABT-199; GDC-0199) is a highly potent, selective and orally bioavailable Bcl-2 inhibitor with a K_i of less than 0.01 nM. Venetoclax induces autophagy.

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.

Navitoclax (ABT-263) is a potent and orally active Bcl-2 family protein inhibitor that binds to multiple anti-apoptotic Bcl-2 family proteins, such as Bcl-x_L, Bcl-2 and Bcl-w, with a K_i of less than 1 nM.

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.

Sorafenib (Bay 43-9006) tosylate 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 tosylate induces cell cycle arrest, autophagy, apoptosis, and PARP cleavage, reduces Bcl-2, Bcl-XL, cyclin D1 levels, and activates Bak and Bax. Sorafenib tosylate inhibits tumor growth and metastasis in mouse and rat models. Sorafenib tosylate can be used for cancer research, such as colon, breast, non-small-cell lung cancer (NSCLC), ovarian, pancreatic, melanoma, colorectal and hepatocellular carcinoma.

BCL-XL-IN-5 is an orally active, highly selective BH3-mimetic BCL-XL inhibitor with a cK_i of 7.96 pM. BCL-XL-IN-5 triggers caspase-3 activation and robust PARP cleavage to initiate apoptosis in BCL-XL-dependent MOLT-4 T-cell acute lymphoblastic leukemia cells. BCL-XL-IN-5 serves as a potent selective probe for investigating BCL-XL-dependent malignancies, such as acute lymphoblastic leukemia.

A-1155463, a chemical probe, is a highly potent and selective BCL-XL inhibitor with an EC₅₀ of 70 nM in Molt-4 cell. A-1155463 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

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.

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.

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.

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.

WEHI-539 hydrochloride is a selective inhibitor of Bcl-XL with an IC₅₀ of 1.1 nM.

Gossypol acetic acid ((±)-Gossypol-acetic acid) binds to Bcl-xL protein and Bcl-2 protein with K_is of 0.5-0.6 μM and 0.2-0.3 mM, respectively.

N-Hydroxyphthalimide is a blocking agent and catalyst. N-Hydroxyphthalimide promotes oxidation reactions by generating PINO free radicals and activating hydrogen atom transfer processes. N-Hydroxyphthalimide reduces the expression of anti-apoptotic proteins Survivin and Bcl-xL and activates caspase 9 and caspase 3. N-Hydroxyphthalimide induces Apoptosis. N-Hydroxyphthalimide inhibits the phosphorylation of mTOR (Ser2448, Ser2481) and Akt (Ser473). N-Hydroxyphthalimide has anticancer effects against breast and colon cancer.

Ganoderma Lucidum/Reishi Extract is a Ganoderma lucidum extract. Ganoderma Lucidum/Reishi Extract reduces the expression of c-Myc, BCL-2, BCL-XL, TERT, PDGFB, eIF4G, Survivin, β-catenin, and eIF4E. Ganoderma Lucidum/Reishi Extract downregulates the gene expression of MMP-9. Ganoderma Lucidum/Reishi Extract upregulates the expression of IL8. Ganoderma Lucidum/Reishi Extract is applicable to the research of inflammatory breast cancer. Ganoderma Lucidum is used in the research of various diseases, such as allergy, arthritis, hypertension, neurasthenia, inflammation, and cancer.

S55746 (BCL201) is a potent, orally active and selective BCL-2 inhibitor, with a K_i of 1.3 nM and a K_d of 3.9 nM. S55746 (BCL201) has antitumor activity with low toxicity.

IGF2BP1-IN-1, a Cucurbitacin B (HY-N0416) derivative, is a potent IGF2BP1 inhibitor (K_D = 2.88 nM). IGF2BP1-IN-1 binds directly to IGF2BP1, thereby inducing tumor cell cycle arrest, increasing apoptosis, and reducing autophagy. IGF2BP1-IN-1 can be used in research on NSLSC, colon, breast, liver, ovarian, pancreatic, and cervical cancers.