Bcl-2 Family Modulator

Kanamycins sulfate is a blood-brain barrier-permeable JNK1 and Bcl-2 modulator as well as an antibiotic, with broad-spectrum antibacterial, and biofilm-inhibiting activities, and it induces autophagy. Kanamycins sulfate promotes Bcl-2 phosphorylation to upregulate autophagy levels, triggering changes such as mitochondrial swelling and endoplasmic reticulum expansion. Consequently, it causes reversible neuronal damage in the dorsal cochlear nucleus without inducing significant neuronal apoptosis. In the presence of exogenous alanine or glucose, Kanamycins sulfate effectively kills drug-resistant bacteria, restores drug sensitivity of multidrug-resistant bacteria, and alleviates urinary tract and kidney infections in mice. Kanamycins sulfate can be applied to scientific research related to Mycobacterium tuberculosis, salmonellosis, brucellosis, shigellosis, urinary tract infections, and reversible neurotoxicity.

Oxychloroaphine could be isolated from the bacterium Pantoea agglomerans naturally present in soil. Oxychloroaphine has broad-spectrum antifungal activity. Oxychloroaphine has cytotoxicity in a dose-dependent manner and induces apoptosis. Oxychloroaphine can be used in research of cancer.

Stem bromelain (EC 3.4.22.32) is a cysteine protease and antibacterial agent. Stem bromelain can be isolated from the stem of the pineapple (Ananas comosus). Stem bromelain induces dose-dependent secretion of IL-12p70, and IL-6, induces Apoptosis, causes cleavage of full-length PARP protein, Caspase 3, and Caspase 9, increases Bax, and decreases Bcl-2. Stem bromelain possesses various fibrinolytic, antiedema, antithrombotic, and anti-inflammatory activities. Stem bromelain also exhibits in vivo antitumor and antileukemic activities, as well as antimetastatic effects. Stem bromelain has antimycobacterial activity. Stem bromelain provides protection against lead poisoning.

Methyl caffeate is a phenylpropanoid, antibacterial agent, and Apoptosis-inducing agent. Methyl caffeate can be isolated from the flowers of peach Prunus persica (L.). Methyl caffeate upregulates the expression of pro-apoptotic proteins Bid, Bax and p53, and downregulates the expression of anti-apoptotic protein BCL-2. Methyl caffeate downregulates SASP factors. Methyl caffeate enhances glucose-stimulated insulin secretion. Methyl caffeate inhibits the growth of Gram-positive bacteria, Gram-negative bacteria, fungi, and Mycobacterium tuberculosis strains. Methyl caffeate can be used in studies related to breast cancer, type 2 diabetes, and tuberculosis.

BETd-260 (ZBC 260) is a BET PROTAC degrader. BETd-260 recruits BRD2, BRD3, and BRD4 to the CUL4-RBX1-DDB1-CRBN E3 ubiquitin ligase complex, driving cereblon-, proteasome-, and NEDD8-activating enzyme-dependent ubiquitination and degradation, with a DC50 of approximately 30-100 pM in RS4;11 cells. BETd-260 induces cancer cell apoptosis via endogenous signaling pathways, regulates the expression of the Bcl-2 family, inhibits the oncogene c-Myc, and reduces cell viability. BETd-260 suppresses tumor growth in mouse xenograft models with good biosafety. BETd-260 can be used in research related to acute leukemia, hepatocellular carcinoma, osteosarcoma, and triple-negative breast cancer.

ROS-generating agent 1 is a selective ROS-generating agent. ROS-generating agent 1 inhibits TrxR activity and expression in cancer cells. ROS-generating agent 1 induces ROS-dependent apoptosis and ferroptosis in cancer cells. ROS-generating agent 1 selectively kills lung cancer cells and inhibits the growth of cancer cell xenograft tumors in nude mice. ROS-generating agent 1 can be used for the research of non-small cell lung cancer.

Kansuinine A is a diterpenoid compound. Kansuinine A is isolated from the roots of Euphorbia kansui. Kansuinine A inhibits H₂O₂-mediated upregulation of phosphorylated IKKβ, NF-κB and IκBα. Kansuinine A inhibits ROS production, reduces the Bax/Bcl-2 ratio and the expression of cleaved Caspase-3. Kansuinine A upregulates the expression of SOCS-3 and blocks IL-6-induced signal transduction. Kansuinine A decreases the expression of LOX-1 and inhibits Apoptosis. Kansuinine A reduces the atherosclerotic lesion area of the aortic arch, improves glucose/insulin tolerance, and enhances antioxidant capacity. Kansuinine A exhibits antiviral and antitumor activities. Kansuinine A can be used in research related to atherosclerosis, liver cancer and type 2 diabetes.

Sodium glycocholate hydrate, 98% is a bile acid derivative. Sodium glycocholate hydrate, 98% downregulates MDR1, Bcl-2, MRP1, MRP2 and FXR, upregulates Bax, p53, caspase-9, caspase-3, TGR5 and S1PR2. Sodium glycocholate hydrate, 98% inhibits multidrug resistance and efflux pumps, induces mitochondrial apoptosis, and enhances chemosensitivity. Sodium glycocholate hydrate, 98% modulates related bile acid receptor signaling. Sodium glycocholate hydrate, 98% suppresses growth and conjugation of Enterobacteriaceae and increases their antibiotic susceptibility. Sodium glycocholate hydrate, 98% can be used for the research of colon adenocarcinoma and cholangiocarcinoma (CCA).

BEPP hydrochloride is a double-stranded RNA-dependent protein kinase (PKR) modulator. BEPP hydrochloride enhances the phosphorylation levels of PKR and eIF2α, activates caspase-3, upregulates the pro-apoptotic protein BAX, and downregulates the anti-apoptotic protein Bcl-2. BEPP hydrochloride inhibits vaccinia virus replication and exhibits selective cytotoxicity in cells expressing PKR. BEPP hydrochloride can be used in research related to cancer and viral infections.

Quinalizarin is a protein kinase CK2 inhibitor with a K_i of 0.052 μM. Quinalizarin exhibits antifungal and anticancer activities. Quinalizarin induces ROS production, apoptotic signaling, mitochondrial pathway activation, cell cycle arrest, and cytotoxicity in cancer cells. Quinalizarin inhibits hyphal growth, biofilm formation, and mature biofilm integrity of Candida albicans. Quinalizarin can be used in research related to cancer and fungal infections.

Dehydrocorydaline (13-Methylpalmatine) hydroxyl is an alkaloid that regulates protein expression of Bax, Bcl-2; activates caspase-7, caspase-8, and inactivates PARP. Dehydrocorydaline hydroxyl elevates p38 MAPK activation. Anti-inflammatory and anti-cancer activities. Dehydrocorydaline hydroxyl shows strong anti-malarial effects (IC50=38 nM), and low cytotoxicity (cell viability > 90%) using P. falciparum 3D7 strain.

Dimebutic acid is an orally active short-chain fatty acid. Dimebutic acid stimulates fetal globin production and alters the balance of Bcl family proteins. Dimebutic acid prolongs red blood cell survival. Dimebutic acid exhibits toxicity in rats. Dimebutic acid can be used in the study of β-thalassemia and sickle cell disease.

Chamaejasmine (Chamaejasmin) is a natural biflavonoid found in the roots of Stellera chamaejasme, exhibiting antitumor activity. Chamaejasmine inhibits Bcl-2, upregulates Bax, and induces cleavage of caspase-9/-3 and PARP. Chamaejasmine induces ROS production, Δψm loss, cytochrome c release, G2/M arrest, apoptosis, and autophagy. Chamaejasmine induces apoptosis and autophagy through activation of AMPK and inhibition of mTOR, and inhibits microtubule depolymerization by binding to β-tubulin. Chamaejasmine inhibits IL-4, IgE, β-hexosaminidase, and mast cell infiltration, and improves skin barrier function in AD models. Chamaejasmine exhibits cytotoxicity against various cancer cells. Chamaejasmine can be used in research related to various cancers such as lung adenocarcinoma and osteosarcoma, as well as atopic dermatitis.

Rehmannioside A is a compound that can be isolated from Rehmanniae radix. Rehmannioside A is an inhibitor of CYP3A4, 2C9 and 2D6, with IC₅₀ values of 10.08, 12.62 and 16.43 μM, respectively. Rehmannioside A has anti-inflammatory, antioxidant, anti-apoptosis, anti-ferroptosis, cognitive improvement and neuroprotective activities. Rehmannioside A can be used for the research of nervous system and inflammation-related diseases.

Macranthoside B is an apoptosis inducer with in vitro and in vivo anticancer activity. Macranthoside B induces autophagy and ferroptosis in cancer cells. Macranthoside B induces intracellular ROS accumulation, activates AMPK, inhibits mTOR and P70S6 kinase phosphorylation, and modulates Bcl-2/Bax expression. Macranthoside B activates caspase-3, caspase-9, and the intrinsic caspase cascade, induces PARP cleavage/degradation, and inhibits NRF2 signaling. Macranthoside B disrupts iron homeostasis via NCOA4-dependent ferritinophagy, up-regulates Lip-ROS, reduces mitochondrial membrane potential, and activates the JNK pathway. Macranthoside B can be used for the research of ovarian cancer, hepatoma, gastric carcinoma, breast carcinoma, colon carcinoma, glioma, melanoma, adenocarcinoma of the esophagogastric junction, and cervical cancer.

Desethylamiodarone hydrochloride (N-Desethylamiodarone hydrochloride; LB 33020 hydrochloride) is the major active metabolite of Amiodarone (HY-14187) generated via CYP3A4 metabolism. Desethylamiodarone hydrochloride downregulates p‑Akt, p‑Bad and Bcl‑2, upregulates Bax, promotes mitochondrial release of cytochrome c, activates caspase‑3 and cleaves PARP‑1, thereby inducing cell cycle arrest and apoptosis. Desethylamiodarone hydrochloride can be used in cervical cancer-related research.

PI-1840 is a potent and selective chymotrypsin-like (CT-L) inhibitor for with an IC₅₀ value of 27 nM. PI-1840 inhibits cell proliferation and arrest cell cycle at G2/M phase. PI-1840 induces apoptosis and induces autophagy. PI-1840 induces the accumulation of proteasome substrates p27, Bax, and IκB-α.

Pim-1 kinase inhibitor 2 is a PIM-1 kinase inhibitor with a human IC₅₀ of 0.63 μM. Pim-1 kinase inhibitor 2 exhibits high selectivity for cancer cells over normal cells. Pim-1 kinase inhibitor 2 induces apoptosis, increases active caspase-3 levels, upregulates BAX, downregulates Bcl-2, and elevates the Bax/Bcl-2 ratio. Pim-1 kinase inhibitor 2 suppresses cancer cell proliferation and induces cell cycle arrest. Pim-1 kinase inhibitor 2 can be used for the research of prostate carcinoma, hepatocellular carcinoma, and breast adenocarcinoma.

Azaleatin is an orally active inhibitor of hQC, NS2B-NS3 protease and E. coli β-glucuronidase, with IC₅₀ values of 1.1 μM, 38.00 μg/mL and 0.57 μM, respectively. Azaleatin inhibits the activities of NF-κB, MyD88, JAK1, TLR4, STAT3, IL-1β, IL-6, COX-2, TNF-α and β-glucuronidase, blocks pro-inflammatory signaling pathways, reduces the levels of ROS, MDA and uric acid, elevates the levels of GPx, GSR, GST, SOD, CAT, HO-1 and GSH, scavenges free radicals and exerts reducing capacity. Azaleatin inhibits the expression of pro-apoptotic proteins Bax, Caspase-9 and Caspase-3, and upregulates the expression of anti-apoptotic protein Bcl-2. Azaleatin reduces the levels of cardiac injury markers, restores cardiac histological structure, inhibits Aβ aggregation, dengue protease activity, hepatic stellate cell proliferation and cancer cell growth, and also exhibits antibacterial activity. Azaleatin can be used in studies related to subchronic cardiotoxicity, Alzheimer's disease, dengue fever, hyperuricemia, liver fibrosis, gastric cancer and bacterial infections.

Continentalic acid is a diterpenoid organic acid. Continentalic acid exhibits multiple activities including anti-inflammatory, antioxidant, neuroprotective, antibacterial and antitumor effects. Continentalic acid alleviates oxidative stress, reduces pro-inflammatory cytokine production, inhibits MAPK phosphorylation and neutrophil infiltration, and induces growth inhibition and apoptosis of cancer cells. Continentalic acid can be used in research related to traumatic brain injury, cancer, inflammation and infections.