Osteosarcoma

Idasanutlin (RG7388) is an orally bioavailable MDM2 inhibitor with an IC₅₀ of 6 nM. Idasanutlin disrupts MDM2-p53 binding, stabilizes and activates p53, triggering cell cycle arrest, apoptosis, and reduced cancer cell viability. Idasanutlin reduces EGFR protein expression and phosphorylation, suppresses downstream SHP2, MEK1/2, ERK1/2, AKT, mTOR, p70(S6K1), and S6 signaling. Idasanutlin induces mitochondrial ROS production, drives p38 MAPK phosphorylation, upregulates NOXA, and mediates caspase-3-dependent apoptosis and gasdermin E-mediated pyroptosis. Idasanutlin can be used for the research of TP53-mutant non-small cell lung cancer, T-cell acute lymphoblastic leukemia, colorectal carcinoma, melanoma, diffuse large B-cell lymphoma, mantle cell lymphoma, non-Hodgkin lymphoma, severe fever with thrombocytopenia syndrome, neuroblastoma, acute lymphoblastic leukemia, relapsed or refractory acute myeloid leukemia, osteosarcoma, solid tumors, and hematological tumors.

FHD-609 is a BRD9 PROTAC degrader. FHD-609 induces BRD9 degradation, downregulates primary transcripts of HBG/HBD, Myc expression and proliferation gene sets, reduces the levels of synovial sarcoma tumor proliferation markers, and inhibits tumor growth. FHD-609 can be used in research related to advanced synovial sarcoma, SMARCB1-deficient tumors and adrenocortical carcinoma.

Samrotamab (PR-1498487) is a humanized IgG1-κ chimeric monoclonal antibody targeting LRRC15, with a K_d of 5.42 nM for human LRRC15. Samrotamab disrupts the LRRC15-SCG5 signaling module by binding to a membrane-proximal conformational epitope within the C-terminal leucine-rich repeat region of LRRC15, which locates at the lateral edge of the LRR solenoid while fully exposing the canonical concave β-sheet surface. Samrotamab reduces the viability of bladder cancer cells, inhibits clonogenic growth, impairs cell migration and compromises cell invasion. Samrotamab induces compensatory upregulation of LRRC15 transcripts while suppressing the expression of SCG5 mRNA. Samrotamab is applicable to research on urothelial carcinoma, sarcoma, osteosarcoma and undifferentiated pleomorphic sarcoma.

ML191 (CID23612552) is a GPR55 antagonist. ML191 inhibits ERK phosphorylation and PKC β II translocation downstream of GPR55 signaling. ML191 suppresses LPI-induced activation of ERK1/2 and p38 MAPK signaling, blocks the transcription of RANKL-induced osteoclastogenesis markers, and reduces the bone resorption activity of mature osteoclasts promoted by RANKL. ML191 can be used to investigate diseases associated with bone degradation caused by excessive osteoclast activation, such as osteoporosis and bone damage during the formation stage of bone metastases.

K2-B4-5e is a BRD4 PROTAC degrader with a DC₅₀ of 6.2 nM. K2-B4-5e triggers the degradation of BRD4 and BRD2 mediated by KLHDC2 in a ubiquitin-proteasome system-dependent manner. K2-B4-5e induces BRD4 degradation in mouse cells. K2-B4-5e can be used in research related to prostate cancer, breast cancer and osteosarcoma.

Ac-HFKLYWPPFLGS-NH2 is a RMI1/2 heterodimer inhibitor with an IC₅₀ of 99 nM and antiproliferative activity. Ac-HFKLYWPPFLGS-NH2 binds competitively at the FANCM-RMI interaction interface, mimics native FANCM MM2 domain hydrophobic interactions, and adopts a unique binding pose with additional protein interactions. Ac-HFKLYWPPFLGS-NH2 induces antiproliferative effects in ALT-positive osteosarcoma cells. Ac-HFKLYWPPFLGS-NH2 shows limited stability toward α-chymotrypsin-mediated enzymatic degradation in vitro. Ac-HFKLYWPPFLGS-NH2 lacks inherent cell permeability, requiring conjugation to a cell-penetrating peptide for intracellular delivery. Ac-HFKLYWPPFLGS-NH2 can be used for the research of ALT-positive osteosarcoma.

tP4-CPP12 is a RMI1/2 heterodimer inhibitor with an IC₅₀ of 110 nM. tP4-CPP12 binds competitively at the FANCM-RMI interaction site and disrupts endogenous FANCM-RMI protein-protein interactions. tP4-CPP12 induces antiproliferative effects in ALT-positive osteosarcoma cells. tP4-CPP12 is applicable for the research of ALT-positive osteosarcoma.

β-actin-IN-1 is a selective and covalent β-actin polymerization inhibitor. β-actin-IN-1 targets Cys272 of β-actin and shows selectivity over α-actin and γ-actin. β-actin-IN-1 inhibits β-actin polymerization and disrupts the actin cytoskeleton in cancer cells, leading to cell migration inhibition as well as cell death. β-actin-IN-1 can be used for the study of osteosarcoma.

TM-2-51 is a HDAC8 activator with a K_d value of 0.28 μM. TM-2-51 inhibits α-glucosidase with an IC₅₀ of 171.21 μM. TM-2-51 upregulates HDAC8 expression, modulates the TP53, STAT3/ERK and PI3K-AKT pathways, alleviates LeTx-induced cell cycle arrest, downregulates JMJD3 and increases H3K27me3 levels. TM-2-51 selectively induces apoptosis in tumor cell and upregulates p53/p21 expression. TM-2-51 inhibits tumor cell proliferation, migration and invasion, induces G₁-phase arrest and suppresses tumor growth in vivo. TM-2-51 can be used in research on osteosarcoma, anthrax, type 2 diabetes and neuroblastoma.

Fucoxanthinol, a carotenoid, is a deacetylated Fucoxanthin (HY-N2302) metabolite with oral activity, and inhibits rat pancreatic lipase with an IC₅₀ of 764 nM. Fucoxanthinol reduces expression of Bcl-2, Bcl-xL, survivin, XIAP, cIAP2, cyclin D1, cyclin D2, cyclin E, CDK4, CDK6, β-catenin, JunD, PPARγ, and induces GADD45α expression. Fucoxanthinol activates caspase-3, caspase-8, caspase-9, Nrf2/Keap1/ARE pathway, and inhibits activation of Akt, NF-κB, AP-1, PDPK1, GSK3β phosphorylation. Fucoxanthinol induces apoptosis, G0/G1 cell cycle arrest, inhibits cancer cell viability, proliferation, migration, invasiveness, tumour growth, adipocyte differentiation, oxidative stress, neurotoxicity, triglyceride absorption, angiogenesis, and obesity-induced inflammation. Fucoxanthinol can be used for the research of osteosarcoma, leukemia, lymphoma, adult T-cell leukemia, prostate cancer, colon cancer, breast cancer, hypertriglyceridaemia, Alzheimer’s disease, Parkinson’s disease, obesity, insulin resistance, malignant melanoma, and type II diabetes.

GDC-0425 hydrochloride (RG-7602 hydrochloride) is an orally active, highly selective ChK1 inhibitor. GDC-0425 hydrochloride abrogates cell cycle arrest and inhibits genomic repair. GDC-0425 hydrochloride potently suppresses Gemcitabine (HY-17026)-induced pCDK1/2 expression. GDC-0425 hydrochloride can be used in research related to osteosarcoma, ovarian cancer, basal (triple-negative) breast cancer, and colorectal cancer.