| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| 10mg | |||
| Other Sizes |
| Targets |
KDM5A (histone lysine demethylase 5A), KDM5B, and KDM5C (pan-KDM5 inhibition). These enzymes are responsible for demethylating histone H3 at lysine 4 (H3K4), a mark associated with active gene transcription. KDM5A-IN-1 shows selectivity for the KDM5 family over other KDM enzymes.
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|---|---|
| ln Vitro |
KDM5A-IN-1 shows IC50 values of 45 nM for KDM5A, 56 nM for KDM5B, and 55 nM for KDM5C. It has an EC50 value of 960 nM for increasing H3K4me3 levels in PC9 cells. The compound is significantly less potent against other KDM enzymes.
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| ln Vivo |
KDM5A-IN-1 (compound 50,5 mg/kg; horny; female CD-1 mice) has a t1/2 of 0.4 hours, moderate elimination in mice (28 mL/min/kg), and good oral bioavailability (F% 34). In diabetic mice, protein binding is significantly low (40%).
KDM5A-IN-1 (Compound 50, 5 mg/kg; oral administration; female CD-1 mice) shows moderate clearance (28 mL/min/kg) in mice with good oral bioavailability (F% 34) and remarkably low plasma protein binding in mice (40%), with a half-life (t₁/₂) of 0.4 hours. The compound is orally bioavailable. |
| Enzyme Assay |
KDM5 enzymatic activity assay: Recombinant KDM5A, KDM5B, or KDM5C is incubated with varying concentrations of KDM5A-IN-1 and a peptide substrate corresponding to histone H3 (residues 1-21) trimethylated at lysine 4 (H3K4me3) in assay buffer (50 mM HEPES pH 7.5, 50 mM KCl, 1 mM DTT, 0.01% Tween-20) at 37°C for 60 min. The reaction is terminated and the demethylated product is detected by a fluorescence-based or antibody-based method (e.g., AlphaScreen or ELISA). IC50 values are calculated.
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| Cell Assay |
H3K4me3 quantification in PC9 cells: PC9 cells are treated with KDM5A-IN-1 at varying concentrations (0.01-10 µM) for 24-72 hours. Cells are harvested, and histones are acid-extracted. H3K4me3 levels are measured by Western blot using anti-H3K4me3 antibody or by ELISA. The EC50 for increasing H3K4me3 is calculated from dose-response curves.
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| Animal Protocol |
Animal/Disease Models: Female CD-1 mice [1]
Doses: 5 mg/kg Route of Administration: Oral (pharmacokinetic/PK/PK study) Experimental Results: Moderate clearance in mice (28 mL/min/kg) with good has oral bioavailability (F% 34) and shows very low plasma protein binding (40%) in mice. Pharmacokinetic study in mice: Female CD-1 mice are administered KDM5A-IN-1 at 5 mg/kg via oral gavage. Blood samples are collected at various time points (0, 0.25, 0.5, 1, 2, 4, 6, 8, 24 h) post-dose. Plasma concentrations are measured by LC-MS/MS. Pharmacokinetic parameters including Cmax, Tmax, AUC, half-life, clearance, and oral bioavailability are calculated. |
| ADME/Pharmacokinetics |
KDM5A-IN-1 shows moderate clearance (28 mL/min/kg) in mice with good oral bioavailability (F% 34) and remarkably low plasma protein binding in mice (40%), with a half-life of 0.4 hours. The compound is orally bioavailable. Molecular weight is 290.37 g/mol.
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| Toxicity/Toxicokinetics |
No detailed toxicity data has been published in the available literature. KDM5A-IN-1 is for research use only. As an epigenetic modulator targeting histone demethylases, potential off-target effects on gene expression should be considered. Standard laboratory safety practices should be followed when handling this compound.
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| References | |
| Additional Infomation |
KDM5A-IN-1 is a potent, orally bioavailable pan-KDM5 inhibitor with IC50 values of 45 nM (KDM5A), 56 nM (KDM5B), and 55 nM (KDM5C). It increases H3K4me3 levels with an EC50 of 960 nM in PC9 cells. The compound shows selectivity for the KDM5 family over other KDM enzymes. It has moderate clearance and good oral bioavailability in mice. No clinical trials or approved上市 status have been reported.
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| Molecular Formula |
C21H28CL2N4O
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|---|---|
| Molecular Weight |
423.38
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| Exact Mass |
290.174
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| CAS # |
1905481-36-8
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| PubChem CID |
119081409
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
592.6±50.0 °C at 760 mmHg
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| Flash Point |
312.2±30.1 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.586
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| LogP |
-1.13
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
21
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| Complexity |
422
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC(C)C1=CC(=NN1)C(=O)N2CC[C@H](C2)NC(=O)C3CC3
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| InChi Key |
CXEXTVGTDZRKJS-LLVKDONJSA-N
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| InChi Code |
InChI=1S/C15H22N4O2/c1-9(2)12-7-13(18-17-12)15(21)19-6-5-11(8-19)16-14(20)10-3-4-10/h7,9-11H,3-6,8H2,1-2H3,(H,16,20)(H,17,18)/t11-/m1/s1
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| Chemical Name |
N-[(3R)-1-(5-propan-2-yl-1H-pyrazole-3-carbonyl)pyrrolidin-3-yl]cyclopropanecarboxamide
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| Synonyms |
KDM5AIN1 KDM5A IN 1 KDM5A-IN-1
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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 : ≥ 50 mg/mL (~172.20 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (9.47 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 27.5 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: ≥ 2.75 mg/mL (9.47 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 27.5 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: ≥ 2.75 mg/mL (9.47 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 | 2.3619 mL | 11.8097 mL | 23.6194 mL | |
| 5 mM | 0.4724 mL | 2.3619 mL | 4.7239 mL | |
| 10 mM | 0.2362 mL | 1.1810 mL | 2.3619 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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