WDR5 Inhibitor

OICR-9429, a chemical probe, is high affinity WD repeat domain 5 (WDR5) inhibitor, competitively blocks WDR5 interaction with MLL protein via binding the central peptide-binding pocket of WDR5. OICR-9429 can suppress histone H3K4 trimethylation and can be used for the research of various cancers including non-MLL-rearranged leukaemia, colon, pancreatic, prostate cancer and bladder cancer (BCa) .

MM-102 (HMTase Inhibitor IX) is a cell-permeable and tightly binding inhibitor of MLL1-WDR5 interaction (IC₅₀=2.4 nM). MM-102 can specifically inhibit the growth and induce apoptosis of leukemia cells containing MLL1 fusion protein, and reduce renal fibrosis and inflammation in mice with ischemia-reperfusion injury. In addition, MM-102 also acts as an H3K4 histone methyltransferase inhibitor to improve the development of porcine somatic cell nuclear transfer (SCNT) embryos.

WDR5-IN-5 is an orally active and selective inhibitor of WIN site of WD repeat domain 5 (WDR5). WDR5-IN-5 exhibits anti-proliferative activity towards cancer cells and good pharmacokinetics profile in mice. WDR5-IN-5 shows high affinity to WDR5 and the binding affinity K_i value <0.02 nM.

DC_M5_2 is a WD40 repeat domain protein 5 (WDR5) inhibitor with an IC₅₀ of 9.63 μM and a K_D of 13.8 μM. DC_M5_2 binds to the WDR5 pocket that interacts with the MLL1 peptide, blocking the WDR5-MLL1 protein-protein interaction. DC_M5_2 can be used in leukemia-related research.

MM-401 (TFA) is a MLL1 H3K4 methyltransferase inhibitor. MM-401 inhibits MLL1 activity (IC₅₀ = 0.32 μM) by blocking MLL1-WDR5 interaction. MM-401 can induce cell cycle arrest, apoptosis and differentiation. MM-401 can be used for the research of MLL leukemia.

WDR5-IN-1 is a potent and selective WD repeat domain 5 (WDR5) inhibitor, with a K_d of <0.02 nM. WDR5-IN-1 inhibits MLL1 histone methyltransferase (HMT) activity with an IC₅₀ of 2.2 nM. WDR5-IN-1 diminishes MYC recruitment at WDR5-displaced genes and exhibits potent anti-proliferative effects in CHP-134 (neuroblastoma) and Ramos (Burkitt’s lymphoma) lines.

MM-102 TFA (HMTase Inhibitor IX TFA) is a potent WDR5/MLL interaction inhibitor, achieves IC50 = 2.4 nM with an estimated Ki < 1 nM in WDR5 binding assay, which is >200 times more potent than the ARA peptide.

WDR5-IN-6 is a WDR5 inhibitor, targeting to WBM site. WDR5-IN-6 inhibits cell proliferation of neuroblastoma cell lines with potent anti-tumor activity. WDR5-IN-6 shows high synergy with OICR-9429 (HY-16993), a WDR5 inhibitor targeting to WIN site. WDR5-IN-6 can be used for reasearch in neuroblastoma.

WM-586 is a covalent WDR5 inhibitor. WM-586 specifically decreases WDR5 and MYC interaction with an IC₅₀ of 101 nM. WM-586 is used in research on a variety of cancers including neuroblastoma, breast cancer, bladder cancer and colorectal cancer.

WDR5-IN-4 (Compound C6) is a WIN site inhibitor of chromatin-associated WD repeat domain 5 protein (WDR5), K_d The value is 0.1 nM. WDR5-IN-4 is able to displace WDR5 from chromatin and reduce the expression of related genes, causing translation inhibition and nucleolar stress. Has anti-cancer effects .

WDR5-IN-4 TFA (Compound C6) is an inhibitor of the WIN site of chromatin-associated WD repeat-containing protein 5 (WDR5), with a K_d of 0.1 nM. WDR5-IN-4 TFA displaces WDR5 from chromatin and decreases the expression of associated genes, causing translational inhibition, nucleolar stress. Anti-cancer activity.

WM-662 is a WDR5-MYC interaction inhibitor, with an IC₅₀ of 18 μM. WM-662 has potential for the research of cancer, aging, and neurodegenerative disorders.

Anticancer agent 126 (compound 12) is a WDR5 inhibitor with anticancer effects. Anticancer agent 126 disrupts WDR5-MYC interaction in cells and reduce MYC target gene expression.

OICR-0547 is a negative control, closely related derivative of OICR-9429 (HY-16993). OICR-9429 is a novel small-molecule antagonist of the Wdr5-MLL interaction. OICR-0547 is an inactive control compound that no longer binds to WDR5.

WDR5-IN-7 (Compound 22) is an orally bioavailable benzoxazepinone-based WD repeat domain 5 (WDR5) inhibitor. WDR5-IN-7 can be used for the research of anti-cancer.

DDO-2213 is an orally active and potent WDR5-MLL1 inhibitor, with an IC₅₀ of 29 nM and a K_d value of 72.9 nM for the WDR5 protein. DDO-2213 selectively inhibits MLL (mixed lineage leukemia) histone methyltransferase activity and the proliferation of MLL translocation-harboring cells. DDO-2213 can be used for MLL fusion leukemia research.

MM-589 TFA is a potent inhibitor of WD repeat domain 5 (WDR5) and mixed lineage leukemia (MLL) protein-protein interaction. MM-589 binds to WDR5 with an IC₅₀ of 0.90 nM and inhibits the MLL H3K4 methyltransferase activity with an IC₅₀ of 12.7 nM.

HBI-2375 (HYBI-084) is a brain-penetrant WDR5 inhibitor with an IC₅₀ of 4.48 nM. HBI-2375 binds to the WINR5 and disrupts MLL1-WDR5 protein-protein interactions. HBI-2375 inhibits cancer cells proliferation and shows anti-tumor activity in AML mouse models, and increases tumor CD8⁺ cytotoxic T lymphocyte infiltration. HBI-2375 inhibits hERG with an IC₅₀ of 17 µM.

CS-VIP 8 hydrochloride is a selective allosteric WDR5 protein inhibitor (K_i= 0.008 μM). CS-VIP 8 hydrochloride induces conformational changes in the MLL1 complex, leading to the dissociation of MLL1 from the complex, inhibiting MLL1 histone methyltransferase activity and regulating HOX gene expression. CS-VIP 8 hydrochloride is promising for research of hematological diseases such as leukemia.

WDR5-0102 is an inhibitor of WDR5. WDR5-0102 specifically targets the WIN site of WDR5, disrupts the WDR5-MLL1 interaction, and reduces the histone methyltransferase activity of MLL1. WDR5-0102 exerts dose-dependent toxicity on MDSC-like cells and reduces their osteopontin levels, while showing extremely low cytotoxicity to pancreatic cancer cells. WDR5-0102 can be used in the research of related diseases such as acute myeloid leukemia, lymphoid leukemia, biphenotypic leukemia and pancreatic cancer.