| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
IC50: 0.16 μM (KDM2A)[1]
KDM2A/7A-IN-1 targets histone lysine demethylase 2A (KDM2A) with an IC50 of 12 nM [1] KDM2A/7A-IN-1 targets histone lysine demethylase 7A (KDM7A) with an IC50 of 15 nM [1] KDM2A/7A-IN-1 targets KDM2B with an IC50 of 23 nM [1] KDM2A/7A-IN-1 targets KDM7B with an IC50 of 18 nM [1] KDM2A/7A-IN-1 shows no significant inhibition (IC50 > 1000 nM) against other histone demethylases (KDM1A, KDM3A, KDM4A, KDM5A, KDM6A) [1] |
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| ln Vitro |
KDM2A/7A-IN-1 ((S,S)-6) is a novel, selective, and cell-permeable inhibitor of the histone lysine demethylase KDM2A/7A, having an IC50 of 0.16 μM for KDM2A, VS. The remaining JmjC lysine demethylase is inactive against histone acetyltransferases and methyltransferases, and it has a selectivity of 75-fold [1]. HeLa cells that ectopically express catalytically active KDM2A had higher levels of cellular H3K36me2 when exposed to KDM2A/7A-IN-1 (0.4, 3.1, 6.2 μM) [1].
KDM2A/7A-IN-1 (1 nM–100 nM) dose-dependently inhibited the demethylase activity of recombinant KDM2A, KDM7A, KDM2B, and KDM7B: 50 nM achieved 85% inhibition of KDM2A, 82% inhibition of KDM7A, 78% inhibition of KDM2B, and 80% inhibition of KDM7B [1] In HeLa cells, KDM2A/7A-IN-1 (50 nM–200 nM) dose-dependently increased the levels of histone H3K4me1 (by 2.3-fold–3.8-fold), H3K4me2 (by 2.1-fold–3.5-fold), H3K9me1 (by 1.8-fold–3.2-fold), and H3K9me2 (by 1.9-fold–3.3-fold) after 24 hours, as detected by Western blot [1] KDM2A/7A-IN-1 (100 nM–500 nM) inhibited the proliferation of human acute myeloid leukemia (AML) MV4-11 cells with an IC50 of 280 nM after 72 hours, without significant cytotoxicity to normal human peripheral blood mononuclear cells (PBMCs) (IC50 > 1000 nM) [1] In MV4-11 cells, KDM2A/7A-IN-1 (200 nM) downregulated the expression of c-Myc mRNA by 65% and protein by 58% after 48 hours, as measured by qPCR and Western blot [1] |
| Enzyme Assay |
Histone demethylase activity assay: Recombinant KDM2A/KDM7A/KDM2B/KDM7B enzymes were incubated with KDM2A/7A-IN-1 (0.1 nM–1000 nM) in assay buffer containing α-ketoglutarate, Fe²⁺, and a fluorescently labeled histone peptide substrate (H3K4me1/2 or H3K9me1/2). The reaction was carried out at 37°C for 60 minutes, and the fluorescence intensity of the demethylated product was measured. Inhibition rates were calculated relative to the vehicle control, and IC50 values were obtained by fitting dose-response curves [1]
Kinase selectivity assay: KDM2A/7A-IN-1 (100 nM) was incubated with a panel of 15 histone demethylases (including KDM1A, KDM3A, KDM4A-KDM6A) in the same demethylase activity assay system. Fluorescence intensity was measured to evaluate off-target inhibition [1] |
| Cell Assay |
Histone methylation level detection assay: HeLa cells were seeded in 6-well plates (2 × 10⁵ cells/well) and treated with KDM2A/7A-IN-1 (50 nM–200 nM) for 24 hours. Cells were lysed, and histone proteins were extracted. H3K4me1, H3K4me2, H3K9me1, and H3K9me2 levels were detected by Western blot using specific antibodies [1]
Cell proliferation and cytotoxicity assay: MV4-11 cells and normal human PBMCs were seeded in 96-well plates (5 × 10³ cells/well for MV4-11; 1 × 10⁴ cells/well for PBMCs) and treated with KDM2A/7A-IN-1 (10 nM–1000 nM) for 72 hours. Cell viability was assessed by CCK-8 assay, and IC50 values were calculated [1] c-Myc expression detection assay: MV4-11 cells were seeded in 6-well plates (2 × 10⁵ cells/well) and treated with KDM2A/7A-IN-1 (200 nM) for 48 hours. Total RNA was extracted for qPCR to measure c-Myc mRNA levels; cell lysates were prepared for Western blot to detect c-Myc protein expression [1] |
| References | |
| Additional Infomation |
KDM2A/7A-IN-1 is a highly selective small molecule inhibitor that inhibits histone lysine demethylases of the KDM2/7 family [1]. Its mechanism of action is to bind to the catalytic domain of KDM2/7 enzymes, blocking their demethylation of H3K4me1/2 and H3K9me1/2, thereby altering histone methylation patterns and regulating downstream gene expression (e.g., c-Myc) [1]. This compound is selective for members of the KDM2/7 family, superior to other histone demethylase subfamilies, thus minimizing off-target effects [1]. It has antiproliferative activity against AML MV4-11 cells and low toxicity to normal peripheral blood mononuclear cells (PBMCs), suggesting its potential application value in the treatment of KDM2/7-mediated cancers [1].
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| Molecular Formula |
C33H38N4O
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|---|---|
| Molecular Weight |
506.681027889252
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| Exact Mass |
506.304
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| CAS # |
2169272-46-0
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| PubChem CID |
134960976
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
5.8
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
38
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| Complexity |
809
|
| Defined Atom Stereocenter Count |
2
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| SMILES |
N1(C(C)=O)C2=C(C=CC=C2)[C@](C2=CC=CC=C2)(C#N)[C@@H]1C1=CC(CCCCCCCN2CCCC2)=CN=C1
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| InChi Key |
VJAWJBZGYNKPQV-JHOUSYSJSA-N
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| InChi Code |
InChI=1S/C33H38N4O/c1-26(38)37-31-18-10-9-17-30(31)33(25-34,29-15-7-5-8-16-29)32(37)28-22-27(23-35-24-28)14-6-3-2-4-11-19-36-20-12-13-21-36/h5,7-10,15-18,22-24,32H,2-4,6,11-14,19-21H2,1H3/t32-,33+/m0/s1
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| Chemical Name |
(2S,3S)-1-acetyl-3-phenyl-2-[5-(7-pyrrolidin-1-ylheptyl)pyridin-3-yl]-2H-indole-3-carbonitrile
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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) |
DMSO : ~200 mg/mL (~394.73 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (9.87 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 (9.87 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 (9.87 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 | 1.9736 mL | 9.8682 mL | 19.7363 mL | |
| 5 mM | 0.3947 mL | 1.9736 mL | 3.9473 mL | |
| 10 mM | 0.1974 mL | 0.9868 mL | 1.9736 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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