mixed-lineage

Menin-MLL inhibitor 20 is an irreversible inhibitor of the menin-MLL interaction, exhibiting antitumor activities.

GW806742X is an inhibitor of Mixed Lineage Kinase Domain-Like protein (MLKL) which binds the MLKL pseudokinase domain (Kd: 9.3 μM) with anti-necroptosis activity. GW806742X has activity against VEGFR2.

URMC-099 is an orally bioavailable, brain penetrant MLK inhibitor (IC50: 19/42/14/150 nM, for MLK1/MLK2/MLK3/DLK), and also inhibits LRRK2 activity (IC50: 11 nM).

Necrosulfonamide ((E)-Necrosulfonamide) is a necroptosis inhibitor that targets MLKL and is selective. Necrosulfonamide prevents the MLKL-RIP1-RIP3 necrosomal complex from interacting with its downstream effectors.

TC-5115 is a highly potent, selective inhibitor of the SET domain of the histone lysine methyltransferase MLL1 (KMT2A), with an IC₅₀ value of 16 nM. TC-5115 exhibits weak inhibitory activity against other methyltransferases such as SET7/9, DOT1L, and EZH2 (IC₅₀ > 1 μM). TC-5115 induces differentiation and growth arrest in leukemia cells and can be used in leukemia research.

M-89, a highly potent and specific inhibitor of the menin-mixed lineage leukemia (Menin-MLL) protein-protein interaction, exhibits a Kd of 1.4 nM for menin binding. This compound holds potential for treating MLL leukemia.

Menin-MLL inhibitor 4 has antitumor activity.Menin-MLL inhibitor 4 is an inhibitor of Menin- MLL (mixed-lineage leukemia protein) interaction .

MM-589 is a potent WD repeat domain 5 (WDR5) inhibitor and mixed lineage leukemia (MLL) protein-protein interaction.

MM-589 TFA is a potent inhibitor of WD repeat domain 5 (WDR5) and a modulator of mixed lineage leukemia (MLL) protein-protein interaction.

TC13172 is a potent and covalent inhibitor that specifically targets the mixed lineage kinase domain-like protein (MLKL), exhibiting significant selectivity for MLKL over the closely related receptor-interacting serine/threonine kinase 1 (RIPK1) and RIPK3 at a concentration of 10 µM.TC13172 effectively inhibits necroptosis induced by the TSZ combination (TNF-α, a Smac mimetic, and Z-VAD-FMK) in HT-29 cells with a EC50 of 2 nM and, at 100 nM, blocks TSZ-induced oligomerization and plasma membrane translocation of MLKL.

Enzomenib is a menin protein inhibitor that disrupts the interaction between menin and mixed lineage leukemia fusion proteins, thereby modulating transcriptional programs driven by MEN gene dysregulation and providing a targeted research tool for mechanistic studies and therapeutic exploration in hematological malignancies associated with menin-dependent oncogenic signaling.

PROTAC MLKL Degrader-2, a PROTAC that targets MLKL (Mixed Lineage Kinase), incorporates the PROTAC target protein ligand, E3 ligase ligand Thalidomide, and PROTAC Linker N-Methylpiperazine. The conjugate of the E3 ubiquitin ligase ligand and Linker is Thalidomide-N-Methylpiperazine. This compound exhibits antinecroptotic activity in human cell lines and effectively degrades MLKL in the HT-29 xenograft mouse model.

MLK3-IN-1 (Compound 37) is a selective inhibitor of mixed-lineage kinase 3 (MLK3) with an IC50 of less than 1 nM. It also inhibits FAK with an IC50 of 15.5 μM. In both murine and human liver microsomes, MLK3-IN-1 demonstrates excellent metabolic stability.

Z116334910 is a competitive WDR5-MLL1 interaction disruptor, where WDR5 (WD Repeat-containing protein 5) is crucial for the methyltransferase activity of the MLL1 (mixed lineage leukemia 1) complex, and can be used for cancer research.

RIPK1-IN-34 is a selective RIPK1 inhibitor capable of penetrating the blood-brain barrier with an IC50 of 126.70 nM, showing minimal inhibition of RIPK3 (IC50 > 10,000 nM). It exerts significant neuroprotective effects by inhibiting the phosphorylation of RIPK1, RIPK3, and mixed lineage kinase domain-like pseudokinase (MLKL) in the necroptosis pathway. RIPK1-IN-34 demonstrates neuroprotective effects in rat models of middle cerebral artery occlusion (MCAO) and is a candidate for research in the treatment of acute ischemic stroke (AIS).

MIV-6 is an inhibitor of the menin-mixed lineage leukemia interaction.

(Iso)-ML399 is an isomer of ML399 exhibiting inhibitory activity against Menin-MLL (Mixed Lineage Leukemia) protein interactions (IC50=1.4 µM), suitable for biochemical experiments and drug synthesis research.

RX-37 is a potent BET inhibitor with Ki values of 3.2-24.7 nM for BRD2, BRD3 and BRD4. RX-37 demonstrates high selectivity over other non-BET bromodomain-containing proteins. RX-37 potently and selectively inhibits cell growth in human acute leukemia cell

SGC0946 is a highly effective and specific DOT1L methyltransferase inhibitor (IC50: 0.3 nM); selectively kill mixed lineage leukemia cells.

GW841819X is an analogue of (+)-JQ1 and a novel inhibitor of BET bromodomains. GW841819X was a single enantiomer but of undefined chirality at the 4-position of the benzodiazepine ring3. GW841819X and JQ1 were recently discovered that bind to the acetyl-lysine binding pocket of BET bromodomains with Kd ranges from 50 to 370 nM [1]. GW841819X bounded to both the individual BD1 and BD2 domains with affinities of 46 and 52.5 nM, respectively. GW841819X-Brd3 interaction was estimated to be around 70 nM4. GW841819X displayed activity in vivo against NUT-midline carcinoma, multiple myeloma, mixed-lineage leukemia, and acute myeloid leukemia1. It also potent induced the ApoA1 reporter gene with an EC50 of 440 nM. It had very little effect on LDL-R luciferase activity at the concentrations at which it induces ApoA1 expression, suggesting that the effect is indeed specific3. GW841819X competed directly with GATA1 site for BD1 binding and also specifically blocked the interaction between Brd3 and acetylated GATA14. Recent findings reported that GW841819X are chose as an interest compound to further develop into potential drugs against diseases including cancer, HIV infection and heart disease2.

MLK-IN-1 is a potent and selective mixed-lineage kinase 3 (MLK-3) inhibitor, showing excellent brain penetration and high specificity for MLK-3. MLK-IN-1 at 100 nM supports sustained axonogenesis in cultures challenged with HIV-1 Tat-activated microglia and protects neuronal cells from Tat-induced damage, establishing it as a valuable probe for neuroinflammation and neurodegeneration research.

Sekikaic acid is a phenolic lichen metabolite that has been found in H. obscurata and has diverse biological activities. It scavenges superoxide and DPPH radicals in cell-free assays when used at a concentration of 0.5 µM. Sekikaic acid is active against the rg recombinant strain of respiratory syncytial virus (RSV; IC50 = 5.69 µg/ml). It inhibits the protein-protein interaction between mixed lineage leukemia 1 (MLL1) and the GACKIX domain of CREB-binding protein (CBP; IC50 = 34 µM).

M‑89 is a Highly Potent Inhibitor of the Menin-Mixed Lineage Leukemia (Menin-MLL) Protein−Protein Interaction (Kd = 1.4 nM; IC50 = 25nM). M-89 binds to menin with a Kd value of 1.4 nM and effectively engages cellular menin protein at low nanomolar concentrations. M-89 inhibits cell growth in the MV4;11 and MOLM-13 leukemia cell lines carrying MLL fusion with IC50 values of 25 and 55 nM, respectively, and demonstrates >100-fold selectivity over the HL-60 leukemia cell line lacking MLL fusion.

GW841819X is an analogue of (+)-JQ1 and a novel inhibitor of BET bromodomains. GW841819X displayed activity in vivo against NUT-midline carcinoma, multiple myeloma, mixed-lineage leukemia, and acute myeloid leukemia. Bromodomain and extra-terminal (BET) proteins belong to a class of proteins collectively called epigenetic readers". BET bromodomains have emerged as promising drug targets for treatment of cancers