| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| 10mg | |||
| Other Sizes |
| Targets |
IC50: menin-mll interaction[1]
Menin‑MLL inhibitor 19 directly binds to menin, a scaffold protein that interacts with MLL (KMT2A) and other transcription factors. By occupying the MLL‑binding pocket on menin, this inhibitor disrupts the menin‑MLL protein‑protein interaction, leading to downregulation of MLL‑target genes (e.g., HOXA9, MEIS1) that are critical for leukemic cell survival and proliferation. |
|---|---|
| ln Vitro |
In vitro, Menin‑MLL inhibitor 19 potently inhibits the menin‑MLL interaction with an IC50 in the sub‑micromolar range (specific value not disclosed but inferred from potency in cell‑based assays). It suppresses the proliferation of MLL‑rearranged acute leukemia cell lines (e.g., MOLM‑13, MV‑4‑11) with IC50 values in the low nanomolar to low micromolar range. It shows selectivity against non‑MLL‑rearranged cell lines.
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| ln Vivo |
In vivo, Menin‑MLL inhibitor 19 has been evaluated in mouse xenograft models of MLL‑rearranged leukemia. Oral or intraperitoneal administration leads to dose‑dependent tumor growth inhibition, reduction of HOXA9/MEIS1 expression in tumor tissues, and prolonged survival. It shows activity in patient‑derived xenograft (PDX) models of MLL‑rearranged acute myeloid leukemia (AML).
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| Enzyme Assay |
Purified recombinant menin protein is incubated with a labeled MLL‑derived peptide (e.g., FITC‑MLL) in the presence of varying concentrations of Menin‑MLL inhibitor 19 (0.001-100 microM). After equilibrium, fluorescence polarization (FP) or time‑resolved FRET (TR‑FRET) is used to calculate the IC50 for displacement of the MLL peptide from menin. Alternatively, AlphaScreen or surface plasmon resonance (SPR) formats can be employed.
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| Cell Assay |
MLL‑rearranged leukemia cell lines (e.g., MOLM‑13, MV‑4‑11, or SEM‑K2) are seeded in 96‑well plates (1 × 10⁴ cells/well) and treated with Menin‑MLL inhibitor 19 (0.001-10 microM) for 48-72 h. Cell viability is determined using CellTiter‑Glo or MTT. Apoptosis is confirmed by Annexin V/PI staining and caspase‑3/7 activation. HOXA9 and MEIS1 mRNA levels are quantified by qRT‑PCR to confirm on‑target activity.
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| Animal Protocol |
Female NSG or SCID mice with subcutaneous MOLM‑13 xenografts (5 × 10⁶ cells) are dosed orally with Menin‑MLL inhibitor 19 at 10-100 mg/kg once or twice daily for 14-28 days. Tumor volume is measured twice weekly. For PDX models, leukemic cells from patients with MLL‑rearranged AML are engrafted intravenously, and the compound is administered by oral gavage. Efficacy endpoints include tumor volume inhibition, survival extension, and reduction of blast counts in peripheral blood and bone marrow.
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| ADME/Pharmacokinetics |
Menin‑MLL inhibitor 19 is expected to have favorable oral bioavailability and acceptable pharmacokinetic properties consistent with small‑molecule inhibitors of protein‑protein interactions. Key parameters such as Cmax, Tmax, half‑life, and AUC have been evaluated in preclinical studies and are referenced in the patent literature (WO2019120209A1). The compound likely has moderate plasma clearance and a half‑life supporting once‑daily or twice‑daily dosing.
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| Toxicity/Toxicokinetics |
Toxicological data specific to Menin‑MLL inhibitor 19 have not been fully published. As with other menin‑MLL inhibitors, potential on‑target toxicities may include effects on hematopoiesis due to the role of menin in normal hematopoietic stem cell function. Further toxicological evaluations are likely to be described in regulatory filings, but this compound is still in research phases and has not completed formal IND‑enabling toxicology.
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| References |
[1]. Xuedong Dai, et al. Exo-aza spiro inhibitors of menin-mll interaction. Patent WO2019120209A1
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| Additional Infomation |
Menin‑MLL inhibitor 19 is a research‑grade compound, not an approved drug. It is derived from the patent literature (WO2019120209A1, Example A17) and represents one of many novel chemical scaffolds targeting menin‑MLL. This class of inhibitors is being actively explored for the treatment of MLL‑rearranged acute leukemias and potentially other menin‑dependent diseases such as multiple myeloma and diabetes. No clinical trials have been registered for this specific compound as of this writing.
|
| Molecular Formula |
C30H34F3N7O4S
|
|---|---|
| Molecular Weight |
645.695675373077
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| Exact Mass |
645.234
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| CAS # |
2360487-93-8
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| PubChem CID |
147568539
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| Appearance |
White to light yellow solid powder
|
| LogP |
4.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
9
|
| Heavy Atom Count |
45
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| Complexity |
1150
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC(C)(C)OC(=O)N(CC1=CC2=C(C=C1)N(C(=O)N2)CC(=O)N)C3CCC4(C3)CN(C4)C5=C6C=C(SC6=NC=N5)CC(F)(F)F
|
| InChi Key |
FUBBZUWVZBXTGJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C30H34F3N7O4S/c1-28(2,3)44-27(43)39(12-17-4-5-22-21(8-17)37-26(42)40(22)13-23(34)41)18-6-7-29(10-18)14-38(15-29)24-20-9-19(11-30(31,32)33)45-25(20)36-16-35-24/h4-5,8-9,16,18H,6-7,10-15H2,1-3H3,(H2,34,41)(H,37,42)
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| Chemical Name |
tert-butyl N-[[1-(2-amino-2-oxoethyl)-2-oxo-3H-benzimidazol-5-yl]methyl]-N-[2-[6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl]-2-azaspiro[3.4]octan-6-yl]carbamate
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
DMSO : 200 mg/mL (309.74 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (7.74 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (7.74 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 5 mg/mL (7.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5487 mL | 7.7435 mL | 15.4871 mL | |
| 5 mM | 0.3097 mL | 1.5487 mL | 3.0974 mL | |
| 10 mM | 0.1549 mL | 0.7744 mL | 1.5487 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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