Neuroblastoma

ARV-825 is a BET protein PROTAC degrader that recruits cereblon, and it targets BRD2, BRD3, and BRD4 for degradation via the ubiquitin-proteasome pathway. ARV-825 downregulates c-MYC, PLK1, MYCN, CDK4/6, JAK2, pSTAT3/5, PIM1, and Bcl-xL, upregulates p21 and p27, and modulates H3K27Ac-mediated transcription, the G2/M checkpoint, the Wnt/β-catenin pathway, and amino acid transport pathways. ARV-825 induces G1 phase cell cycle arrest, caspase 3/PARP-mediated apoptosis, DNA damage, and reactive oxygen species (ROS) production, reduces mitochondrial respiration, and simultaneously inhibits cell proliferation, clonogenic growth, and cell migration. ARV-825 is used in research on gastric cancer, leukemia, neuroblastoma, and cholangiocarcinoma.

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.

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.

JQAD1 is a EP300 PROTAC degrader. JQAD1 selectively targets EP300 and induces its degradation via the CRBN-dependent proteasomal pathway. JQAD1 reduces the levels of H3K27ac and the expression of MYCN. JQAD1 induces apoptosis (apoptosis) and inhibits cancer cell growth. JQAD1 exerts anti-neuroblastoma effects in vivo in a CRBN-dependent manner. JQAD1 can be used for the research of neuroblastoma.

dBET57 is a potent and selective BRD4_BD1 PROTAC degrader with a DC₅₀ of approximately 500 nM. dBET57 forms a ternary complex with CRL4^CRBN and BRD4_BD1, induces the ubiquitination and degradation of BRD4, and indirectly inhibits the transcription of MYCN, c-Myc and PD-L1, ultimately leading to cell cycle arrest and apoptosis. dBET57 can be used in related research on neuroblastoma, non-small cell lung cancer and colorectal cancer.

dAurAB5 is a potent Aurora-A/Aurora-B PROTAC degrader with DC₅₀ values of 8.8 nM and 6.1 nM, respectively. dAurAB5 promotes proteasomal degradation of target proteins, induces ubiquitination of Aurora-A and Aurora-B kinases, and downregulates the protein levels of TTK and MYCN. dAurAB5 can be used in studies related to neuroblastoma[1].

SK2188 (JB325) is a selective AURKA PROTAC degrader with a DC₅₀ of 3.9 nM. SK2188 recruits CRBN E3 ubiquitin ligase to target and degrade AURKA, abrogating both its catalytic and non-kinase functions, which leads to the destabilization and degradation of the oncogenic protein MYCN, ultimately inducing replication stress, DNA damage and apoptosis. SK2188 is applicable to research related to neuroblastoma.

SK2187 (JB301) is a selective AURKA PROTAC degrader. SK2187 induces targeted degradation of AURKA by recruiting the CRBN E3 ubiquitin ligase. SK2187 is applicable to research related to neuroblastoma.

SK-3-91 is a multi-kinase PROTAC degrader that induces the degradation of the maximum number of unique kinases (over 125 distinct kinases) simultaneously. SK-3-91 induces protein degradation via the ubiquitin biotinylation (E-STUB) pathway, such as inducing the degradation of YTHDF2. SK-3-91 also inhibits cell proliferation and induces cell morphological changes. SK-3-91 can be used in research related to acute lymphoblastic leukemia, multiple myeloma, neuroblastoma, ovarian cancer, mantle cell lymphoma, and gastric cancer.

U7D-1 is a USP7 PROTAC degrader that induces selective proteasomal degradation of USP7. U7D-1 destabilizes and downregulates the expression of variant PRC1 complex subunits PCGF1, RING1A and PCGF6, and also slightly reduces the protein level of KDM2B. U7D-1 decreases cell viability, arrests neuroblastoma cells at the G0/G1 cell cycle phase, and downregulates the expression of target genes of PAX3::FOXO1 in FP-RMS cells. U7D-1 increases the level of cleaved PARP in FP-RMS cells, induces cell apoptosis, and upregulates the expression of muscle differentiation markers MYH1 and MYF5. U7D-1 inhibits the growth and proliferation of p53 wild-type and mutant cancer cells, and regulates the apoptosis pathway and E2F pathway. U7D-1 is applicable to studies on neuroblastoma, fusion-positive rhabdomyosarcoma, p53-mutant cancers and cancer-related research.

HLB-0532259 is a Aurora-A/N-Myc PROTAC degrader, with a DC₅₀ of 20.2 nM against Aurora-A in MCF-7 cells; its DC₅₀ values against N-Myc are 179 nM in SK-N-BE (2) cells and 229 nM in Kelly cells, respectively. HLB-0532259 induces apoptosis (apoptosis) in MYCN-amplified neuroblastoma cells and inhibits tumor growth in mouse xenograft models. HLB-0532259 can be used for the research of neuroblastoma.

TL13-12 is a CRBN-recruiting ALK PROTAC degrader, with a DC₅₀ of 10 nM in H3122 cells. TL13-12 induces dimerization of CRBN and truncated ALK, which brings the DNA-binding domain and transactivation domain into close proximity, thereby activating the expression of downstream reporter genes, while exhibiting extremely low leaky expression under non-inducing conditions. TL13-12 serves as a tool molecule for the orthogonal PROTAC-CID system, and is applied in research on non-small cell lung cancer, anaplastic large cell lymphoma, and neuroblastoma.

10-Deacetyltaxol (10-Deacetylpaclitaxel) is a taxane derivative found in Taxus wallichiana Zucc. and exhibits cytotoxicity against human neurotumor cell lines. It shows a concentration-dependent cytotoxic effect on cancer cells and demonstrates activity in the mouse leukemia system. 10-Deacetyltaxol can be used for research on neuroblastoma, glioblastoma multiforme, and lymphocytic leukemia.

Prostaglandin A1 is a dehydrated derivative of Prostaglandin E1. Prostaglandin A1 exhibits antiviral, anti-inflammatory, antitumor, neuroprotective, and antihypertensive activities. Prostaglandin A1 covalently binds to cysteine residues of target proteins through Michael addition, or activates pathways such as PPARγ and HSPs via transcriptional regulation. Prostaglandin A1 is used in research on Mayaro virus infection, stroke, Alzheimer's disease, neuroblastoma, melanoma, and severe gestational hypertension.

β-NF-JQ1 is a BRD2/3/4 PROTAC degrader. β-NF-JQ1 recruits the AhR E3 ligase complex to BRD2, BRD3 and BRD4, induces AhR-BRD interaction, and mediates AhR-dependent degradation through the proximity effect between the target protein and AhR. β-NF-JQ1 acts as an antiproliferative and cytotoxic agent that induces anticancer activity associated with BRD protein knockdown. β-NF-JQ1 can be used for research on breast cancer and neuroblastoma.

Nitrovin (Difurazon) hydrochloride is an orally active inhibitor of thioredoxin reductase 1 (TrxR1) with both antibacterial and anticancer activities. Nitrovin hydrochloride induces ROS generation and endoplasmic reticulum stress by targeting and inhibiting TrxR1, which in turn induces cytoplasmic vacuolation, activates MAPK, and inhibits Alix. Nitrovin hydrochloride induces paraptosis-like non-apoptotic cell death, thereby exerting significant cytotoxicity against cancer cells. Nitrovin hydrochloride is used for research on glioblastoma, liver cancer, and bacterial infections.

dAurAB2 is a potent Aurora-A/Aurora-B PROTAC degrader with DC₅₀ values of 59 nM and 39 nM, respectively. dAurAB2 induces ubiquitination and proteasomal degradation of Aurora-A kinase and Aurora-B kinase, and indirectly reduces N-Myc protein levels. dAurAB2 can be used in studies related to neuroblastoma.

TO-1187 is a selective HDAC6 PROTAC degrader with a DC₅₀ value of 5.81 nM. TO-1187 degrades HDAC6 via the ubiquitin-proteasome pathway. TO-1187 can be used in the research of multiple myeloma, neuroblastoma, and cervical cancer.

AP-1 is a targeted ALK PROTAC degrader. AP-1 effectively degrades various ALK fusion/mutation forms, including degradation of NPM-ALK (DC₅₀ = 4.6 nM) and EML4-ALK (DC₅₀ = 357.6 nM), and exhibits a typical hook effect at high concentrations. AP-1 inhibits phosphorylation of downstream STAT3, downregulates gene expression in the JAK-STAT pathway, and kills ALK-positive tumor cells via activating the caspase-3-dependent apoptosis pathway. AP-1 shows cytotoxicity against a variety of cancer cells and possesses anti-tumor activity. AP-1 can be used in research related to non-small cell lung cancer, neuroblastoma, and anaplastic large cell lymphoma.

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.