Menin-MLL inhibitor MI-2 (MI2) is a potent menin-MLL interaction inhibitor with IC50 of 446 nM.

Menin-MLL Inhibitor 29 (Compound C1) is a Menin-MLL protein-protein interaction (PPI) inhibitor that demonstrates high affinity to Menin with a dissociation constant (K D) of 138 nM and impedes Menin's interaction with Menin-binding motif 1 (MBM1), as evidenced by an inhibition constant (IC 50) of 46 nM. Additionally, it exhibits anti-proliferative activity against HepG2 and Hep3B hepatoma cell lines with IC 50 values of 0.31 μM and 0.71 μM, respectively, and has been shown to inhibit tumor growth [1].

(1s,4s)-Menin-MLL Inhibitor-23, an enantiomer of Menin-MLL Inhibitor-23 (Example 99A), functions as an inhibitor of the menin-MLL interaction [1].

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

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.

Menin-MLL inhibitor 27 effectively inhibits the interaction between Menin and MLL, serving as a potential tool in cancer research, particularly for acute myeloid leukemia (AML) [1].

Menin-MLL inhibitor 26 is a Menin-MLL inhibitor. Menin-MLL inhibitor 26 also is an active reference. Menin-MLL inhibitor 26 can inhibits cell growth. Menin-MLL inhibitor 26 can be used for the research of leukemia .

Menin-MLL inhibitor 20 is an irreversible inhibitor of menin-MLL interaction with antitumor activities.

Menin-MLL Inhibitor 24 (compound A) oxalate, a menin-mixed-lineage leukemia 1 (menin-MLL) inhibitor, is utilized in cancer research [1].

MI-3 (Menin-MLL Inhibitor) (Menin-MLL Inhibitor) is an effective inhibitor of Menin-MLL interaction (IC50: 648 nM).

VTP50469 is a highly selective and orally active inhibitor of Menin-MLL interaction( Ki: 104 pM) and has potently anti-leukemia activity.

MM-102 (HMTase Inhibitor IX) is a high-affinity peptidomimetic MLL1 inhibitor with IC50 of 0.4 μM.

SNDX-5613 is a potent and specific inhibitor of Menin-MLL(Ki of 0.149 nM and a cell based IC50 of 10-20 nM). SNDX-5613 can be used for the research of MLL-rearranged (MLL-r) acute leukemias.

MIV-6R inhibits Menin-MLL interaction (IC50: 56 nM) and can be used to study leukemia.

SGC-iMLLT is a potent and selective MLLT1/3-histone interactions inhibitor(IC50 = 0.26 μM),and is a first-in-class chemical probe displaying cellular target engagement of MLLT1(Kd = 0.129 μM) and MLLT3(Kd = 0.077 μM).

NVS-MLLT-1 is a selective inhibitor of YEATS domain of MLLT1 and MLLT3.

OICR-9429 is a potent antagonist of the interaction that WDR5 effect with peptide regions of MLL and Histone 3. It reduces the viability of acute myeloid leukemia cells in vitro.

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

M-808 is a potent and efficacious covalent inhibitor, targeting the interaction between Menin and MLL. It demonstrates a high binding affinity with an IC50 value of 2.6 nM.

DDO-2213 is a potent, orally active inhibitor of the WDR5-MLL1 interaction, demonstrating an IC50 of 29 nM and a Kd of 72.9 nM against WDR5. It selectively inhibits MLL (mixed lineage leukemia) histone methyltransferase activity, and suppresses the proliferation of cells harboring MLL translocations, positioning it as a valuable tool for MLL fusion leukemia research [1].

VTP50469 fumarate is a highly selective and orally active inhibitor of Menin-MLL interaction (Ki: 104 pM), and has potently anti-leukemia activity.

I-CBP112 is a selective inhibitor of the bromodomain-containing transcription factors. I-CBP112 (1 mM) has little activity against other bromodomains. I-CBP112 targets the CBP/p300 bromodomains. I-CBP112 significantly reduced the leukemia-initiating poten

CCI 007 is a selective inhibitor of MLL-r, CALM-AF10 and SET-NUP214 leukemia with IC50 of 3.5 uM against MLL-r leukemia cell line PER-485

BRD4-IN-4 is a selective BRD4 inhibitor with an IC50 value of 6.83 μM for BRD4.BRD4-IN-4 selectively inhibits the proliferation of the MV4-11 cell line and arrests the cells in G1 phase.BRD4-IN-4 can be used to study MLL leukemias.

AS-99 TFA is a first-in-class, potent and selective ASH1L histone methyltransferase inhibitor (IC50= 0.79 μM, Kd= 0.89 μM) with anti-leukemic activity. AS-99 TFA blocks cell proliferation, induces apoptosis and differentiation, downregulates MLL fusion target genes, and reduces the leukemia burden in vivo[1]. AS-99 TFA is tested against a panel of 20 histone methyltransferases, including NSD1, NSD2, NSD3, and SETD2. NO significant inhibition is observed at 50 μM of AS-99 TFA on any of the tested histone methyltransferases, indicating over 100-fold selectivity towards ASH1L[1].AS-99 TFA shows effect on the growth of the MLL leukemia cells (MV4;11, MOLM13, KOPN8, RS4;11) with the GI50 values ranging from 1.8 μM to 3.6 μM[1].AS-99 (1-8 μM; 7 days) TFA also induces apoptosis in the MLL leukemia cells, but not in the K562 cells, as assessed by the quantification of the Annexin V positive cells[1].AS-99 TFA suppresses MLL fusion driven transcriptional programs[1]. AS-99 (30 mg/kg; i.p.; q.d., treated for 14 consecutive days) TFA reduces leukemia burden in mice[1].AS-99 TFA is used for in vivo studies in mice, which reveals favorable exposure in plasma upon i.v. and i.p. administration (AUC = 9701 hr* ng/mL and 10,699 hr* ng/mL, respectively), suitable half-life (~5-6 h) and Cmax >10 μM[1]. [1]. David S. Rogawski, Jing Deng, Hao Li, Tomasz Cierpicki, Jolanta Grembecka, et al. Discovery of first-in-class inhibitors of ASH1L histone methyltransferase with anti-leukemic activity. Nat Commun. 2021 May 14;12(1):2792.

M 1121 is a covalent and orally active inhibitor of the menin-MLL interaction capable of achieving complete and persistent tumor regression.

MI-538 is an interaction between menin and MLL fusion proteins inhibitor(IC50 of 21 nM).

ORY-1001 is a KDM1A inhibitor (IC50 <20nM) with high selectivity against related FAD dependent aminoxidases (MAO-A/B, IL4I1, KDM1B >100uM, SMOX 7uM). Treatment of THP-1 (MLL-AF9) cells with ORY-1001, results in a time/dose dependent me2H3K4 accumulation a

MI-2-2 is an inhibitor of bivalent protein-protein interaction between menin and MLL with an IC50 of 46 nM. MI-2-2 binds to menin with Kd of 22 nM.

Iptacopan hydrochloride hydrate is a highly potent and highly selective factor B inhibitor.

CCI-006, a selective inhibitor and chemosensitizer for MLL-rearranged leukemia cells, disrupts mitochondrial respiration. This action leads to irreversible mitochondrial depolarization and triggers a pro-apoptotic unfolded protein response in specific MLL-r leukemia cells.

MI-1481 is an effective MML1 inhibitor (IC50: 3.6 nM). MI-1481 showed very potent inhibition of the menin-MLL1 interaction (IC50: 3.6 nM). MI-1481 also demonstrates pronounced activity in MLL leukemia cells and in vivo in MLL leukemia models.

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.

DDO-2093, a powerful inhibitor of the MLL1-WDR5 protein-protein interaction (IC50 = 8.6 nM; Kd = 11.6 nM), exhibits prominent antitumor effects. Notably, DDO-2093 selectively hampers the catalytic activity of the MLL complex.

ML399 is the menin-- MLL interaction inhibitor that acts by demonstrating strong and selective effects in MLL leukemia cells and validating specific mechanism of action.

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

MI-136 inhibits expression of androgen receptor (AR) target genes that DHT induced.

VTP-50469 is a novel, potent, selective, orally-available MeninMLL1 inhibitor, being effectively against MLL-rearranged and NPM1c+ leukemia, selectively killing cell lines with MLLrearrangements and NPM1c+ mutations.

Dot1L-IN-7 (compound 25) is a selective and potent inhibitor of telomere silencing 1-like protein (DOT1L) (IC50: 1.0 μM).Dot1L-IN-7 selectively kills MLL-AF9 and does not affect the growth of E2A-HLF cells.

OICR-0547 is a closely related derivative of OICR-9429. OICR-9429 is a novel small-molecule Wdr5-MLL interaction antagonist.

DDO-2093 dihydrochloride, a potent inhibitor of MLL1-WDR5 protein-protein interactions (IC50=8.6 nM; Kd=11.6 nM), exhibits antitumor activity. It selectively inhibits the catalytic activity of the MLL complex.

AS-99 is a first-in-class, potent, and selective inhibitor of the ASH1L histone methyltransferase, exhibiting anti-leukemic activity with an IC50 value of 0.79 µM and a Kd of 0.89 µM. It inhibits cell proliferation, induces apoptosis and differentiation, downregulates MLL fusion target genes, and effectively reduces leukemia burden in vivo.

MM-401 (TFA), an MLL1 H3K4 methyltransferase inhibitor, effectively impedes MLL1 activity (IC 50 = 0.32 µM) by preventing MLL1-WDR5 interaction. It can induce cell cycle arrest, apoptosis, and differentiation, offering potential for MLL leukemia research [1].

AS-99 is a first-in-class, potent and selective ASH1L histone methyltransferase inhibitor (IC50= 0.79 μM, Kd= 0.89 μM) with anti-leukemic activity. AS-99 blocks cell proliferation, induces apoptosis and differentiation, downregulates MLL fusion target genes, and reduces the leukemia burden in vivo[1]. AS-99 is tested against a panel of 20 histone methyltransferases, including NSD1, NSD2, NSD3, and SETD2. NO significant inhibition is observed at 50 μM of AS-99 on any of the tested histone methyltransferases, indicating over 100-fold selectivity towards ASH1L[1].AS-99 shows effect on the growth of the MLL leukemia cells (MV4;11, MOLM13, KOPN8, RS4;11) with the GI50 values ranging from 1.8 μM to 3.6 μM[1].AS-99 (1-8 μM; 7 days) also induces apoptosis in the MLL leukemia cells, but not in the K562 cells, as assessed by the quantification of the Annexin V positive cells[1].AS-99 suppresses MLL fusion driven transcriptional programs[1]. AS-99 (30 mg/kg; i.p.; q.d., treated for 14 consecutive days) reduces leukemia burden in mice[1].AS-99 is used for in vivo studies in mice, which reveals favorable exposure in plasma upon i.v. and i.p. administration (AUC = 9701 hr* ng/mL and 10,699 hr* ng/mL, respectively), suitable half-life (~5-6 h) and Cmax >10 μM[1]. [1]. David S. Rogawski, Jing Deng, Hao Li, Tomasz Cierpicki, Jolanta Grembecka, et al. Discovery of first-in-class inhibitors of ASH1L histone methyltransferase with anti-leukemic activity. Nat Commun. 2021 May 14;12(1):2792.

HXR9 is a cell-permeable peptide that acts as a competitive antagonist of the HOX/PBX interaction. It effectively inhibits the binding between HOX proteins and the transcription factor PBX, specifically in paralogue groups 1 to 8. HXR9 selectively impairs cell proliferation and induces apoptosis in cells with a high expression of the HOXA/PBX3 genes, for instance, MLL-rearranged leukemic cells.

TC-5115 is a potent inhibitor of MLL methyltransferase with IC50 value of 16 nM. TC-5115 may lead to the development of a new therapy for the treatment of human MLL leukemia. The mixed-lineage leukemia (MLL) protein, also known as MLL1, is a lysine methyltransferase specifically responsible for methylation of histone 3 lysine 4. MLL has been pursued as an attractive therapeutic target for the treatment of acute leukemia carrying the MLL fusion gene or MLL leukemia.

Ziftomenib (KO-539) is an inhibitor of menin-MLL interaction with antitumor activity and can be used to study leukemia.

MI-2 (Menin-MLL Inhibitor) is an effective menin-MLL interaction inhibitor (IC50: 446 ± 28 nM).

MM-102 TFA (HMTase Inhibitor IX TFA) is a potent WDR5/MLL interaction inhibitor, achieves IC50 = 2.4 nM. MM-102 compound prevents the interaction between mixed lineage leukemia 1 (MLL1) and WD Trp-Asp repeat domain 5 (WDR5) and results in the inhibition of MLL1 H3K4 histone methyltransferase (HMT) activity. Down-Regulation of H3K4me3 by MM-102 Facilitates Epigenetic Reprogramming of Porcine Somatic Cell Nuclear Transfer Embry

MI-463 is a potent and orally bioavailable inhibitor of the menin-mLL interaction (IC50: 15.3 nM).