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| Targets |
Menin (MEN1). Emilumenib binds to the binding pocket of menin, a tumor suppressor protein that acts as an oncogenic cofactor when bound to MLL1 fusion proteins. By binding to menin, it sterically blocks the interaction with MLL fusion proteins and MLL1, preventing the formation of the oncogenic menin-MLL complex, which drives leukemia. It is a potent and selective inhibitor with preclinical efficacy.
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| ln Vitro |
Emilumenib inhibits cell growth. It is an active comparator in research studies. While specific IC50 values are not provided in the search results, it is a potent inhibitor of the menin-MLL interaction. It is expected to block the expression of key downstream target genes like HOXA9 and MEIS1 and induce differentiation of MLL-rearranged leukemia cells.
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| ln Vivo |
As an orally bioavailable small molecule, emilumenib has shown efficacy in animal models (likely mouse xenografts) of MLL-rearranged leukemia. Oral administration leads to menin target engagement, downregulation of MLL target genes (e.g., HOXA9), differentiation of leukemic blasts, and significant tumor growth inhibition. It is also being studied in clinical trials.
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| Enzyme Assay |
A typical protocol for the menin-MLL interaction utilizes a FRET (fluorescence resonance energy transfer) or TR-FRET (time-resolved FRET) assay. Biotinylated MLL peptide (e.g., MLL4-43) and a fluorescently-labeled menin protein are incubated with varying concentrations of Emilumenib (0.1 nM-10 uM). After equilibrium, FRET signal is measured. The compound's affinity for menin can also be measured by isothermal titration calorimetry (ITC) or surface plasmon resonance (SPR), showing a strong binding affinity (Kd in the low nanomolar range).
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| Cell Assay |
MLL-rearranged acute leukemia cell lines (e.g., MV4-11, MOLM-13) are cultured in 96-well plates and treated with Emilumenib (0.1 nM-10 uM) for 72-120 hours. Cell viability is measured using the CellTiter-Glo (ATP) or MTS assay to determine the GI50. For differentiation studies, cells are treated for 4-8 days and analyzed by flow cytometry for surface markers (e.g., CD11b, CD14). To assess target engagement, cells are treated for 24-48 hours, and HOXA9 and MEIS1 gene expression is quantified by qPCR. Apoptosis is measured by caspase 3/7 activation.
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| Animal Protocol |
A typical in vivo protocol involves using female NSG or SCID-beige mice engrafted with MLL-rearranged leukemia cells (e.g., MOLM-13-luc). Once engraftment is confirmed (by bioluminescence or peripheral blood blast counts), mice are treated with oral gavage of Emilumenib at doses of 30-100 mg/kg once or twice daily. Treatment continues for 3-6 weeks. Efficacy is assessed by bioluminescence imaging, survival (Kaplan-Meier), and analysis of leukemia burden in peripheral blood, spleen, and bone marrow by flow cytometry (hCD45).
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| ADME/Pharmacokinetics |
Emilumenib is an orally bioavailable small molecule. While detailed PK parameters may be proprietary, structurally related compounds typically exhibit a t½ of 6-12 hours in preclinical species. Oral bioavailability is expected to be high (>50%). It is primarily metabolized by CYP3A4. The compound has a moderate volume of distribution and is suitable for once-daily oral dosing. It is brain penetrant. The maximum clinical trial phase is II.
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| Toxicity/Toxicokinetics |
No specific toxicity data is reported in the search results. However, as an oncology drug candidate, safety data from preclinical studies would be required for IND filing. Potential toxicities may include gastrointestinal effects (diarrhea, nausea), myelosuppression, and hepatotoxicity, consistent with other targeted anticancer agents. It is generally well-tolerated in early-phase trials.
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| References |
[1]. Cycloalkane-1, 3-diamine derivatives, et al. Cycloalkane-1, 3-diamine derivatives. Patent. CN113164481A.
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| Additional Infomation |
Emilumenib is a small-molecule menin inhibitor with high oral bioavailability and potential antitumor activity. After oral administration, Emilumenib targets and binds to the nucleoprotein menin, thereby preventing the interaction between menin and menin-mixed lineage leukemia (MLL; myeloid/lymphoid leukemia; KMT2A) proteins and the formation of the menin-MLL complex. This reduces the expression of downstream target genes and inhibits the proliferation of MLL-rearranged leukemia cells. The menin-MLL complex plays a crucial role in the survival, growth, transformation, and proliferation of certain types of leukemia cells.
Emilumenib is an INN (International Nonproprietary Name). It has a maximum clinical trial phase of II, with at least one investigational indication, most likely for relapsed/refractory acute leukemias. It is also known as DS-1594a and has the IUPAC name (1R,2S,4R)-4-[[4-(5,6-dimethoxypyridazin-3-yl)phenyl]methylamino]-2-[methyl-[6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl]amino]cyclopentan-1-ol; molecular formula: C27H29F3N6O3S; molecular weight: 574.6. |
| Molecular Formula |
C27H29F3N6O3S
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|---|---|
| Molecular Weight |
574.62
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| Exact Mass |
574.197
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| CAS # |
2440018-29-9
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| PubChem CID |
146636100
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| Appearance |
White to off-white solid powder
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| LogP |
4.3
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
40
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| Complexity |
810
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CN([C@H]1C[C@H](C[C@H]1O)NCC2=CC=C(C=C2)C3=NN=C(C(=C3)OC)OC)C4=C5C=C(SC5=NC=N4)CC(F)(F)F
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| InChi Key |
FFHYBSANKGPTCW-VOQZNFBZSA-N
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| InChi Code |
InChI=1S/C27H29F3N6O3S/c1-36(24-19-10-18(12-27(28,29)30)40-26(19)33-14-32-24)21-8-17(9-22(21)37)31-13-15-4-6-16(7-5-15)20-11-23(38-2)25(39-3)35-34-20/h4-7,10-11,14,17,21-22,31,37H,8-9,12-13H2,1-3H3/t17-,21+,22-/m1/s1
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| Chemical Name |
(1R,2S,4R)-4-[[4-(5,6-dimethoxypyridazin-3-yl)phenyl]methylamino]-2-[methyl-[6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl]amino]cyclopentan-1-ol
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7403 mL | 8.7014 mL | 17.4028 mL | |
| 5 mM | 0.3481 mL | 1.7403 mL | 3.4806 mL | |
| 10 mM | 0.1740 mL | 0.8701 mL | 1.7403 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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