Osteosarcoma

CX-5461 is a selective, orally active RNA polymerase I inhibitor. CX-5461 disrupts the formation of the SL1-rDNA complex, thereby blocking the transcription initiation of ribosomal RNA without altering the activity of RNA polymerase II, DNA replication, or protein translation processes. CX-5461 upregulates the expression of p21, MDM2, Sestrin1/2, and phosphorylated AMPKα, and reduces the level of phosphorylated Akt. CX-5461 induces G2/G2/M cell cycle arrest, Autophagy, Apoptosis, and cellular senescence, and activates CHK1, CHK2, and RPA. CX-5461 can be used in research related to osteosarcoma, cervical cancer, hematologic malignancies, high-grade serous ovarian cancer, and solid tumors.

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.

CX-5461 dihydrochloride is a selective, orally active RNA polymerase I inhibitor. CX-5461 dihydrochloride disrupts the formation of the SL1-rDNA complex, thereby blocking the transcription initiation of ribosomal RNA without altering the activity of RNA polymerase II, DNA replication, or protein translation processes. CX-5461 dihydrochloride upregulates the expression of p21, MDM2, Sestrin1/2, and phosphorylated AMPKα, and reduces the level of phosphorylated Akt. CX-5461 dihydrochloride induces G2/G2/M cell cycle arrest, Autophagy, Apoptosis, and cellular senescence, and activates CHK1, CHK2, and RPA. CX-5461 dihydrochloride can be used in research related to osteosarcoma, cervical cancer, hematologic malignancies, high-grade serous ovarian cancer, and solid tumors.

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 can be used to synthesize antibody-drug conjugates (ADC). Samrotamab disrupts the LRRC15-SCG5 signaling module, binds to a membrane-proximal conformational epitope within the C-terminal leucine-rich repeat region of LRRC15, and binds to the lateral edge of the LRR solenoid while leaving the canonical concave β-sheet surface fully exposed. 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 related to urothelial carcinoma, sarcoma, osteosarcoma, and undifferentiated pleomorphic sarcoma.

Omburtamab (Mab 8H9) is a mouse monoclonal immunoglobulin G1 (IgG1) antibody targeting B7-H3. Omburtamab specifically binds to the glycoprotein antigen B7-H3, which is widely expressed on the surface of tumor cells. As a targeting carrier for recombinant toxins, it delivers PE38 to inhibit cellular protein synthesis and induce cytotoxicity in antigen-expressing cancer cells. Omburtamab can be used in research related to glioma, breast cancer, osteosarcoma and neuroblastoma.

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.

Homo-PROTAC pVHL30 degrader 1 is a Homo-PROTAC autodegraders targeting the von Hippel-Lindau E3 ubiquitin ligase (VHL), with K_d values of 11 nM and 25 nM for pVHL19-EloBC​ and pVHL30-EloBC​, respectively. Homo-PROTAC pVHL30 degrader 1 induces Cullin2 depletion, promotes VHL dimerization to form a ternary complex, and drives proteasome-dependent and CRL2-VHL-like ubiquitination-dependent autodegradation. Homo-PROTAC pVHL30 degrader 1 does not trigger hypoxic responses, and only causes extremely mild stabilization of hypoxia-inducible factor α subunits. Homo-PROTAC pVHL30 degrader 1 can be used in studies related to cervical cancer and osteosarcoma.

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.

BT-O2C is a p300 PROTAC degrader. BT-O2C induces p300 degradation via proteasome- and ubiquitin-like modification-dependent pathways, downregulates the expression of CIC::DUX4 sarcoma target genes, and exerts cytotoxicity against such sarcoma cells. BT-O2C can be used in CIC::DUX4 sarcoma-related studies.

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.

Idasanutlin-d₃-1 (RG7388-d₃-1) is the deuterated-labeled Idasanutlin (HY-15676). 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.

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.

SW393109 is a CDK8 inhibitor with an IC₅₀ of 3.16 nM and an EC₅₀ of 5 nM against the DKK1 reporter gene. SW393109 inhibits IFNγ-induced phosphorylation of STAT1 S727, impairs the EWSR1::FLI1 transcriptional program in Ewing sarcoma cells and suppresses tumor cell proliferation. SW393109 acts as a gain-of-function molecular trap that induces the retention of the CDK8 kinase module (CKM) and Mediator complex on chromatin. SW393109 can be used in studies related to Ewing sarcoma.

NEP162 is a BRD4 PROTAC degrader based on the E3 ubiquitin ligase GID4, with DC₅₀ values of 1.2 μM and 1.6 μM in SW480 and U2OS cells, respectively, and a K_d value of 0.13 µM for GID4. NEP162 bridges the E3 ligase GID4 and BRD4 to form a ternary complex, promotes polyubiquitination and subsequent degradation of BRD4 via the ubiquitin-proteasome system, reduces the proliferation capacity of tumor cells and induces apoptosis. NEP162 can be used for research on cancers such as osteosarcoma, colorectal cancer and non-small cell lung cancer.

MYCMI-7 hydrobromide is a potent and selective MYC/MYCN inhibitor, with a K_d of 4 μM for MYC and an IC₅₀ of 10 μM for topoisomerase IIα (Topoisomerase IIα). MYCMI-7 hydrobromide binds directly to MYC, selectively inhibits the interactions of MYC:MAX and MYCN:MAX, reduces MYC-driven transcription levels, induces MYC/MYCN protein degradation, and blocks the binding of MYC to chromatin, thereby inducing tumor cell growth arrest, apoptosis and reducing cell viability, while only inducing G1 phase growth arrest in normal cells. MYCMI-7 hydrobromide can be used in research related to MYC-driven acute myeloid leukemia and breast cancer, MYCN-amplified neuroblastoma, glioblastoma, Burkitt's lymphoma, melanoma, colon cancer, osteosarcoma, cervical cancer and histiocytic lymphoma.

FD1-C10-CB is a PROTAC degrader targeting the BRD4 protein. FD1-C10-CB binds to FEM1B to form a ternary complex with BRD4, achieving FEM1B-dependent degradation of BRD4 via the ubiquitin-proteasome system. FD1-C10-CB binds to CD36 to mediate endocytic cellular delivery, thereby enhancing its degrading activity. FD1-C10-CB mediates protein degradation through the Cullin-dependent ubiquitin-proteasome pathway, rather than the lysosomal autophagy pathway. FD1-C10-CB induces a decrease in BRD4 protein levels, and its degrading activity is competitively inhibited by FL47 or JQ1. FD1-C10-CB can be used in the research of breast cancer and osteosarcoma.

Faridoxorubicin (AVA-6000) is a FAP-activated chemotherapeutic prodrug. Faridoxorubicin undergoes selective hydrolysis by FAP, while it is resistant to cleavage by related mammalian peptidases and members of the DASH subfamily. Faridoxorubicin acts as a tumor growth inhibitor, reducing tumor volume and prolonging survival in in vivo models and PDX models with high FAP expression. Faridoxorubicin can be used in the research of osteosarcoma and sarcoma.

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.