| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
LSD1 (lysine specific demethylase 1) – IC50 = 0.07 μM (HRP-coupled assay), 0.01 μM (TR-FRET assay), 0.02 μM (MS assay)
MAO-A (monoamine oxidase A) – IC50 = 0.51 μM MAO-B (monoamine oxidase B) – IC50 = 2.785 μM [1] |
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| ln Vitro |
With an IC50 value of roughly 100–200 μM, RN-1 dihydrochloride is cytotoxic to ovarian cancer cells (SKOV3, OVCAR3, A2780, and cisplatin inhibitor A2780cis) [3].
RN-1 is a potent and selective inhibitor of LSD1. In three orthogonal biochemical assay formats (HRP-coupled, TR-FRET, and direct mass spectrometry), RN-1 demonstrated nanomolar IC50 values against recombinant human LSD1. It is a mechanism-based irreversible inhibitor, forming a covalent adduct with the enzyme-bound FAD cofactor. Dilution experiments confirmed that the inhibition is not reversible. RN-1 also showed inhibitory activity against MAO-A and MAO-B, but with lower potency, providing selectivity for LSD1 over the MAOs (e.g., ~6- to 400-fold depending on the assay). [1] |
| ln Vivo |
RN-1 dihydrochloride (3–10 mg/kg; i.p.; daily; for 2 or 4 weeks) effectively induces fetal hemoglobin (HbF) levels in red blood cells and decreases disease pathology in SCD [2]. In /6 rats, concentrations in the brain/arterial exposure ratio was 88.9 after 24 hours of intraperitoneal administration of RN-1 dihydrochloride (10 mg/kg).
Systemic administration of RN-1 (10 mg/kg, i.p.) immediately following training completely abolished long-term memory formation in the novel object recognition (NOR) task in mice when tested 24 hours later. However, it did not affect short-term memory formation when tested 90 minutes after training. [1] |
| Enzyme Assay |
HRP-coupled assay: Recombinant human LSD1 (Δ1-157) was incubated with a dimethylated H3K4 peptide substrate. Demethylation by LSD1 produces H2O2, which reacts with ADHP (10-acetyl-3,7-dihydroxyphenoxazine) in the presence of horseradish peroxidase (HRP) to generate a fluorescent oxidation product. Fluorescence intensity is proportional to enzyme activity. Inhibitors were pre-incubated with enzyme for 10 minutes before substrate addition, and the reaction proceeded for 20 minutes. IC50 values were determined from dose-response curves.
TR-FRET assay: This assay directly detects the H3K4Me1 product generated by LSD1 demethylation of an H3K4Me2 peptide substrate using time-resolved fluorescence energy transfer (TR-FRET). The assay was performed in a multi-label plate reader format. Direct Mass Spectrometry (RapidFire MS) assay: The LSD1 demethylation reaction was performed under identical conditions to the HRP assay. Reactions were quenched with formic acid, and the conversion of H3K4Me2 to H3K4Me1 and H3K4Me0 products was directly quantified using an automated mass spectrometry system (RapidFire-MS) coupled to a triple quadrupole mass spectrometer. Product ion peaks were monitored for quantification. [1] |
| Cell Assay |
Lineage-marker-negative (Lin⁻) bone marrow cells from SCD mice were cultured and induced to undergo terminal erythroid differentiation. After one day of culture, cells were infected with an adenovirus expressing PGC-1α (Ad-PGC-1α) or GFP (Ad-GFP) as a control. Infected cells were harvested at indicated times for QRT-PCR, western blot, and flow cytometric analyses. Overexpression of PGC-1α led to increased human fetal γ-globin and murine embryonic εγ- and βh1-globin mRNA levels. [2]
For in vitro erythroid differentiation assays, human primary erythroid cells were differentiated from mobilized CD34⁺ progenitor cells and treated with RN-1 (0.5 µM) alongside comparators (HU, TC, DAC). γ-globin accumulation was assessed. [2] |
| Animal Protocol |
Animal/Disease Models: Sickle cell disease (SCD) mice [2]
Doses: 3mg/kg or 10mg/kg Route of Administration: ip; 1 dihydrochloride Dramatically impairs long-term memory, but not short-term memory [1 ]. Routine; 2 or 4 consecutive weeks Experimental Results: Effectively induced HbF levels in red blood cells and diminished disease pathology in SCD mice. Memory Formation (Novel Object Recognition):** C57BL/6 male mice were trained in an arena with two identical objects for 10 minutes. Immediately after training, mice were administered a single intraperitoneal injection of RN-1 (10 mg/kg) or vehicle. For long-term memory testing, mice were returned to the arena 24 hours later with one familiar and one novel object, and exploration times were recorded for 10 minutes. For short-term memory testing, a different group of mice were trained similarly and tested 90 minutes after training. [1] **Pharmacokinetics Study:** C57BL/6 male mice received a single intraperitoneal administration of RN-1 (10 mg/kg). Blood and brain tissues were collected at multiple time points up to 24 hours post-dose. Plasma and brain homogenates were analyzed for RN-1 concentrations using LC-MS/MS. [1] Memory Formation (Novel Object Recognition): C57BL/6 male mice were trained in an arena with two identical objects for 10 minutes. Immediately after training, mice were administered a single intraperitoneal injection of RN-1 (10 mg/kg) or vehicle. For long-term memory testing, mice were returned to the arena 24 hours later with one familiar and one novel object, and exploration times were recorded for 10 minutes. For short-term memory testing, a different group of mice were trained similarly and tested 90 minutes after training. [1] Pharmacokinetics Study: C57BL/6 male mice received a single intraperitoneal administration of RN-1 (10 mg/kg). Blood and brain tissues were collected at multiple time points up to 24 hours post-dose. Plasma and brain homogenates were analyzed for RN-1 concentrations using LC-MS/MS. [1] |
| ADME/Pharmacokinetics |
Following a single intraperitoneal administration of RN-1 (10 mg/kg) in male C57BL/6 mice, the maximum plasma concentration (Cmax) was 541.7 ng/mL with a Tmax of 0.08 hours. The area under the plasma concentration-time curve from time zero to infinity (AUCinf) was 17,661.2 hrng/mL. In the brain, the Cmax was 11,390.5 ng/mL with a Tmax of 2.0 hours, and the AUCinf was 157,682.4 hrng/mL. The brain-to-plasma exposure ratio (AUCinf brain/AUCinf plasma) was 88.9. The brain homogenate binding of RN-1 was 95.5% bound. [1]
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| Toxicity/Toxicokinetics |
No overt adverse side effects were observed in SCD mice treated daily with RN-1 at doses up to 10 µg/g for 4 weeks. Serum chemistry analysis showed diminished levels of total bilirubin, lactate dehydrogenase, aspartate transaminase, and alanine transaminase in a dose- and time-dependent manner, indicating reduced hemolysis and liver stress. Urinalysis parameters showed clearance of protein and bilirubin after treatment, with no other treatment-related effects. [2]
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| References |
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| Additional Infomation |
RN-1 is a brain-penetrant, irreversible LSD1 inhibitor derived from the Parnate (tranylcypromine) scaffold. It is a potent and selective inhibitor of LSD1 compared to MAO-A and MAO-B. The study demonstrates that inhibition of LSD1 by RN-1 can block long-term memory consolidation without affecting short-term memory in mice, highlighting the role of LSD1-mediated histone demethylation in memory formation. [1]
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| Exact Mass |
451.179
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|---|---|
| CAS # |
1781835-13-9
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| PubChem CID |
129626553
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
30
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| Complexity |
492
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| Defined Atom Stereocenter Count |
2
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| SMILES |
Cl.Cl.O=C(CNC1CC1C1C=CC(=CC=1)OCC1C=CC=CC=1)N1CCN(C)CC1
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| InChi Key |
WMHAFZOOUBPQRX-VSIGASKDSA-N
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| InChi Code |
InChI=1S/C23H29N3O2.2ClH/c1-25-11-13-26(14-12-25)23(27)16-24-22-15-21(22)19-7-9-20(10-8-19)28-17-18-5-3-2-4-6-18/h2-10,21-22,24H,11-17H2,1H32*1H/t21-,22+/m0../s1
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| Chemical Name |
2-(((trans)-2-(4-(Benzyloxy)phenyl)cyclopropyl)amino)-1-(4-methylpiperazin-1-yl)ethanone Dihydrochloride
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| Synonyms |
RN1 RN 1 RN-1 Dihydrochloride
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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) |
H2O : ~20 mg/mL (~44.21 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 20 mg/mL (44.21 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).
(Please use freshly prepared in vivo formulations for optimal results.) |
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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