c-Myc Inhibitor

STAT3-IN-46 is a selective and orally active inhibitor of signal transducer and activator of transcription 3 (STAT3) (K_D = 323.3 nM). STAT3-IN-46 directly binds to the SH2 domain of the STAT3 and inhibits IL-6/JAK/STAT3 signaling pathway (IC₅₀ = 0.87 μM) and downregulates c-Myc and Bcl-2 levels. STAT3-IN-46 can be used for the research of cancer, such as triple-negative breast cancer.

MLS-2384 free base is a dual JAK/Src kinase inhibitor. MLS-2384 free base downregulates STAT3 downstream proteins c-Myc and Mcl-1. MLS-2384 free base induces Apoptosis. MLS-2384 free base exhibits anticancer activity against prostate cancer, breast cancer, skin cancer, ovarian cancer, lung cancer, and liver cancer.

VGN50 is a bioactive molecule that mimics the function of K-Rta and down-regulates MYC-mediated gene transcription. VGN50 has antitumor activity.

COG449 (OP449) is a cell-penetrating peptide that binds to SET, prevents the formation of the SET-PP2A complex, and restores PP2A phosphatase activity. COG449 decreases the phosphorylation levels of AKT³⁰⁸, ERK1/2, NFkB p65, and c-MYC S62, and reduces c-MYC stability and target gene expression. COG449 induces apoptosis, autophagy, and histone H3 hyperacetylation, and decreases the levels of SET, CIP2A, SETBP1, and Mcl-1. COG449 reduces cancer cell viability and decreases tumor mass in xenograft models. COG449 can be used for research on various cancers such as oral squamous cell carcinoma, T-cell acute lymphoblastic leukemia, B-CLL, non-Hodgkin lymphoma, and breast cancer.

c-Myc inhibitor 14 (Compound 13A) is a c-Myc protein inhibitor. The IC₅₀ value of HL60 inhibitor is <100 nM. c-Myc inhibitor 14 shows antitumor activity.

PROTAC LZK degrader 1 is an LZK (MAP3K13) PROTAC degrader. PROTAC LZK degrader 1 binds LZK with a K_d of 35 nM and recruits VHL E3 ubiquitin ligase to induce ubiquitin-proteasome dependent degradation of LZK in MAP3K13-amplified HNSCC cells. PROTAC LZK degrader 1 eliminates both kinase-dependent c-MYC stabilization and kinase-independent GOF p53 accumulation downstream of LZK, suppresses colony formation of LZK-amplified head and neck squamous cell carcinoma (HNSCC) cells. PROTAC LZK degrader 1 can be used for research on LZK-driven HNSCC.

c-Myc inhibitor 15 (Compound A5) is a selective c-Myc inhibitor that exerts anticancer effects by disrupting the interaction between c-Myc and Max, leading to the degradation of c-Myc protein and the induction of apoptosis. Its IC₅₀ values are 4.08 μM and 7.86 μM in A549 and NCI-H1299 lung cancer cell lines, respectively, demonstrating strong cytotoxic activity. In a syngeneic tumor model, c-Myc inhibitor 15 exhibited outstanding antitumor efficacy, achieving a tumor growth inhibition rate of 76.4% and significantly reducing c-Myc protein expression levels. c-Myc inhibitor 15 holds promise for research related to c-Myc-driven lung cancers.

PHA-680626 is an effective inhibitor of the interaction between Aurora-A and N-Myc. PHA-680626 inhibits kinase activity of AURKA and Bcr-Abl, and induces N-Myc degradation. PHA-680626 decreases phosphorylation of CrkL and histone H3. PHA-680626 shows anti-proliferative and pro-apoptotic activity on Imatinib (HY-15463)-resistant chronic myeloid leukemia cell lines and primary CD34+ cells.

WNY0824 (PLK1/BRD4-IN-1) is an orally active dual inhibitor of PLK1 and BET protein families, with IC₅₀ values ​​of 22, 402.5, 150.7, 103.9, and 311.9 nmol/L for PLK1, BRD2, BRD3, BRD4, and BRDT, respectively. WNY0824 induces cell cycle arrest and apoptosis by inhibiting AR- and MYC-mediated transcriptional processes. In addition, WNY0824 also inhibits tumor growth in Enzalutamide (HY-70002) resistant CRPC xenograft tumor models.

c-Myc inhibitor 10 (compound 17), a c-Myc inhibitor, exhibits increased cellular potency, consistent with an increase in permeability with methylation of the morpholine nitrogen.

MYRA-A is a potent apoptosis inducer in a Myc-dependent manner. MYRA-A inhibits Myc transactivation and interferes with the DNA-binding activity of Myc family proteins. MYRA-A inhibits cell viability.

PROTAC BET Degrader-15 is a BET PROTAC degrader with DC₅₀ values of <0.10 nM, <0.01 nM, and <0.01 nM against BRD2, BRD3, and BRD4, respectively. PROTAC BET Degrader-15 induces significant G2/M phase cell cycle arrest and triggers apoptosis. PROTAC BET Degrader-15 causes marked downregulation of c-Myc, accompanied by upregulation of the cell cycle inhibitory protein p21, downregulation of CDK6, and an increase in the apoptosis marker cleaved PARP. PROTAC BET Degrader-15 is applicable to the research of hematologic malignancies and lung cancer.

CDK8-IN-20 (Compound 67j) is a selective, potent and orally active type I CDK8 inhibitor with an IC₅₀ of 70.5 nM. CDK8-IN-20 shows IC₅₀ values of 147.8, 726.9 and 217.4 nM for homologous kinase CDK19, CDK7 and CDK9. CDK8-IN-20 can inhibit the Wnt/β-catenin pathway and downregulate the expression of β-catenin, Cyclin D1, and c-Myc. CDK8-IN-20 can induce ROS production and cause G2/M and S phase arrest. CDK8-IN-20can be used for the research of cancer, such as colon cancer.

LCI40 is an orally active dual PI3K/BRD4 inhibitor (PI3Kα IC₅₀ = 0.071 μM, PI3Kβ IC_{50 =} 0.17 μM, PI3Kγ IC₅₀ = 0.66 μM, PI3Kδ IC₅₀ = 0.072 μM, BRD4 BD1 IC₅₀ = 0.19 μM, and BRD4 BD2 IC₅₀ = 1.88 μM. LCI40 inhibits phosphorylation of pAKT (S473) and suppresses c-MYC levels in mantle cell lymphoma cells. LCI40 displays immunomodulatory capacity with minimal toxicity to normal mouse immune cells. LCI40 can be used for the research of mantle cell lymphoma.

USP1-IN-20 is an orally effective and selective USP1 inhibitor with an IC₅₀ of 3.0 nM. USP1-IN-20 inhibits the USP1-UAF1 complex, leading to the accumulation of Ub-PCNA, which in turn induces DNA damage and G2/M phase arrest, while simultaneously promoting the degradation of the oncogenic protein c-MYC. USP1-IN-20 can be used for research on breast cancer and diffuse large B-cell lymphoma.

PIN1-IN-8 is a covalent inhibitor of Pin1, with IC₅₀ values of 4.19 μM and 1.54 μM against purified Pin1 and Pin1 enzymatic activity, respectively. PIN1-IN-7 exerts antiproliferative effects and induces apoptosis by downregulating c-Myc and Cyclin D1. PIN1-IN-7 can be used in the research of triple-negative breast cancer.

Y502-2304 is a c-Myc G-quadruplex stabilizer. Y502-2304 exhibits potent antiproliferative activity in multiple myeloma (MM) cells. Y502–2304 downregulates c-Myc mRNA and protein expression. Y502-2304 induces apoptosis in MM cells, characterizes by elevated γH2AX levels, increases reactive oxygen species (ROS) generation, and mitochondrial dysfunction. Y502-2304 significantly inhibits tumor growth in a xenograft MM model. Y502-2304 can be used for the study of multiple myeloma.

GXF-111 is a BRD3 and BRD4-L PROTAC degrader. Its BD1 and BD2 Ki values against human BRD3 are 11.97 nM and 2.45 nM, respectively. The degradation activity of GXF-111 depends on its binding to BET proteins and Cereblon, as well as the involvement of a functional proteasome. The degradation selectivity of GXF-111 is mainly determined by differences in degradation kinetics and cell types. GXF-111 induces G₁ phase cell cycle arrest, downregulates c-Myc expression, upregulates p21 expression, and exhibits antiproliferative activity against a variety of cancer cell lines. GXF-111 can serve as a research tool for cancer-related studies.

CDK9/CycT1 degrader-1 is an autophagy-anchored bifunctional degrader that mediates the degradation of the CDK9/cyclin T1 protein complex. CDK9/CycT1 degrader-1 binds both CDK9 and LC3B simultaneously to form a ternary complex, achieving target protein degradation via the autophagy-lysosome pathway. CDK9/CycT1 degrader-1 downregulates the protein levels of Mcl‑1 and c‑Myc and induces apoptosis. PROTAC CDK9/CycT1 Degrader-2 is applicable to cancer-related research.

AF9/ENL-DOT1L/AF4 PPI-IN-1 is a potent AF9/ENL and histone methyltransferase DOT1L/AF4 protein-protein interactions (PPI) inhibitor. AF9/ENL-DOT1L/AF4 PPI-IN-1 can inhibit the AF9-DOT1L (IC₅₀ = 1.5 μM), AF9-AF4 (IC₅₀ = 1 μM), ENL-AF4 (IC₅₀ = 1.2 μM) interactions. AF9/ENL-DOT1L/AF4 PPI-IN-1 can suppress the expression of Mixed lineage leukemia (MLL) target genes Myc and Meis1 and selectively block the proliferation of MLL-r and several other leukemia cells. AF9/ENL-DOT1L/AF4 PPI-IN-1 exhibits significant antitumor activities in a mouse model of MLL-r leukemia without overt toxicities. AF9/ENL-DOT1L/AF4 PPI-IN-1 can be used for the study of MLL-r leukemia.