c-Myc Degrader

Tambiciclib (GFH009, JSH-009) is an orally active, highly potent and selective CDK9 inhibitor (IC₅₀ = 1 nM), demonstrating >200-fold selectivity over other CDKs, >100-fold selectivity over DYRK1A/B, and excellent selectivity over 468 kinases/mutants. Tambiciclib demonstrates potent in vitro and in vivo antileukemic efficacy in acute myeloid leukemia (AML) mouse models by inhibiting RNA Pol II phosphorylation, downregulating MCL1 and MYC, and inducing apoptosis. Tambiciclib can be used for AML research.

MYC-RIBOTAC is a nucleic acid-targeting degrader (ribonuclease-targeting chimera, RIBOTAC) that targets the MYC internal ribosome entry site (IRES). MYC-RIBOTAC contains a MYC mRNA binding component and a small molecule that recruits and locally activates RNAse L1. MYC-RIBOTAC reduces MYC mRNA and protein expression levels, induces cell apoptosis, and can be used for antitumor research. MYC-RIBOTAC consists of pre-miR-155 binder Anticancer agent 167 (HY-156839), RNA binder NCI-B16 (HY-156215), and Linker Amino-PEG4-alcohol (HY-W008005).

GT19630 is an orally active c-Myc PROTAC targeted degrader based on the cereblon E3 ubiquitin ligase, with an IC₅₀ of 1.5 nM against human c-Myc. GT19630 mediates the degradation of MYC, GSPT1, GSPT2, CK1 alpha, N-Myc, B7-H3 and XIAP, and disrupts the MYC-GSPT1 synergistic regulatory feedback loop. GT19630 inhibits cell proliferation, blocks S-phase progression of the cell cycle, promotes cell apoptosis, reduces cell migration capacity, induces integrated stress response, and blocks oxidative phosphorylation by inhibiting the TCA cycle. GT19630 can be used in the research of Myc-driven hematological cancers, small cell lung cancer, breast cancer, TP53-mutant cancers, and venetoclax-resistant cancers.

MDEG-541 is a PROTAC degrader targeting MYC, GSPT1/2 and PLK1. MDEG-541 induces degradation via proteasome- and ubiquitin-dependent pathways. MDEG-541 exhibits anti-tumor activity in gastrointestinal cancer cells and patient-derived organoids. MDEG-541 can be used for the research of gastrointestinal cancer.

KL4‑219A is a more durable MYC degrader derived from structural optimization of KL2‑236, with its inactive diastereomer being KL4‑219B. KL4‑219A induces destabilization and degradation of MYC protein in a proteasome-dependent manner. KL4‑219A is applicable to the research of pancreatic cancer.

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.

MYC degrader 1 TFA is a MYC degrader that recruits Cereblon (CRBN), with a K_d value of 145 nM and oral activity. MYC degrader 1 TFA specifically binds MYC and GSPT1, recruits the CRBN E3 ubiquitin ligase complex, and induces MYC degradation via the ubiquitin-proteasome pathway. MYC degrader 1 TFA downregulates KLHL42 expression, restores pRB1 protein levels, and re-establishes the sensitivity of MYC-overexpressing cancer cells to CDK4/6 inhibitors. MYC degrader 1 TFA combined with Palbociclib (HY-50767) shows significant inhibition of tumor growth. MYC degrader 1 TFA can be used in studies related to bladder cancer, prostate cancer, and breast cancer.

Tambiciclib (GFH009, JSH-009) dimaleate is an orally active, highly potent and selective CDK9 inhibitor (IC₅₀ = 1 nM), demonstrating >200-fold selectivity over other CDKs, >100-fold selectivity over DYRK1A/B, and excellent selectivity over 468 kinases/mutants. Tambiciclib dimaleate demonstrates potent in vitro and in vivo antileukemic efficacy in acute myeloid leukemia (AML) mouse models by inhibiting RNA Pol II phosphorylation, downregulating MCL1 and MYC, and inducing apoptosis. Tambiciclib dimaleate can be used for AML research.

PLK1-IN-13 is a selective and orally active PLK1 inhibitor (IC₅₀: 0.27 nM). PLK1-IN-13 also inhibits PLK2 (IC₅₀: 12.72 nM) and PLK3 (IC₅₀: 4.12 nM). PLK1-IN-13 arrests cell at G2 phase, induces apoptosis and down-regulates the transcription of the proliferation-related oncogene c-MYC. PLK1-IN-13 inhibits tumor growth, and can be used for research of acute myeloid leukemia (AML).

MTP3 is a MYC PROTAC Degrator. MTP3 facilitates ternary complex formation with CRBN, driving proteasome-dependent full-length MYC degradation and partially proteasome-independent N-terminal truncated MYC (tMYC) generation. MTP3 induces tMYC formation across multiple cancer cell lines with context-dependent response variability. MTP3 can be used for the research of prostate cancer, breast cancer.

CSI86 is a c-MYC PROTAC degrader. CSI86 inhibits the proliferation of various cancer cells and exhibits excellent cellular uptake capacity. CSI86 maintains stability for 72 h in cell culture medium. CSI86 can be used in studies related to breast cancer and prostate cancer.

MTP3 ligand-1 is a MTP3 ligand for PROTAC MTP3 degrade-1 (HY-173467). PROTAC MTP3 degrade-1 is a PROTAC based MYC degrader.

BRD4-IN-12 is a potent and orally active BRD4 inhibitor with an IC₅₀ of 7.9 nM. BRD4-IN-12 downregulates the expression of c-MYC, BCL-2, CDK4 and upregulates p21. BRD4-IN-12 inhibits tumor cell proliferation and promotes apoptosis. BRD4-IN-12 exhibits excellent antitumor effects in the HCT-116 colorectal cancer xenograft model. BRD4-IN-12 can be used for the study of colorectal cancer (CRC).