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Iadademstat (ORY-1001; RG6016) 2HCl, the dihydrochloride salt of ORY1001, is a novel, orally bioactive and selective lysine-specific demethylase LSD1/KDM1A inhibitor with antineoplastic activity. It inhibits LSD1/KDM1A with an IC50 of<20 nM, and shows high selectivity against related FAD dependent aminoxidases. ORY-1001 is an enantiomerically pure (trans conformation) KDM1A inhibitor. It exhibits excellent antiproliferative activity and high in vivo antitumor efficacy. ORY-1001 does not inhibit non-related histone modifiers, and is clean in a CEREP diversity panel. Treatment of THP-1 cells with ORY-1001, results in a time/dose dependent me2H3K4 accumulation at KDM1A target genes and concomitant induction of differentiation markers.
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Physicochemical Properties
| Molecular Formula |
C15H22N2.2HCL
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| Molecular Weight |
303.27
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| Exact Mass |
302.131
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| CAS # |
1431326-61-2
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| Related CAS # |
1431326-61-2 (2HCl) 1431303-72-8 (2HCl) 1431303-71-7 (xHCl) 1431304-21-0
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| PubChem CID |
71664305
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
19
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| Complexity |
239
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| Defined Atom Stereocenter Count |
2
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| SMILES |
N(C1CCC(CC1)N)[C@@H]1C[C@H]1C1C=CC=CC=1.Cl.Cl
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| InChi Key |
UCINOBZMLCREGM-RNNUGBGQSA-N
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| InChi Code |
InChI=1S/C15H22N2.2ClH/c16-12-6-8-13(9-7-12)17-15-10-14(15)11-4-2-1-3-5-11;;/h1-5,12-15,17H,6-10,16H2;2*1H/t12?,13?,14-,15+;;/m0../s1
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| Chemical Name |
4-N-[(1R,2S)-2-phenylcyclopropyl]cyclohexane-1,4-diamine;dihydrochloride
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| Synonyms |
ORY1001; RG 6016;ORY-1001; RG-6016;ORY1001; RG6016; ORY1001 dihydrochloride, ORY1001 HCl; ORY1001 2HCl salt. |
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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
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| 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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Biological Activity
| ln Vitro |
In vitro activity: In THP-1 (MLL-AF9) cells, ORY-1001 results in a time/dose dependent me2H3K4 accumulation at KDM1A target genes and concomitant induction of differentiation markers. ORY-1001 also induces apoptosis in THP-1 and inhibits proliferation and colony formation of MV(4;11) (MLL-AF4) cells.
Kinase Assay: ORY-1001 (RG-6016) is an orally active and selective lysine-specific demethylase LSD1/KDM1A inhibitor with IC50 of<20 nM, with high selectivity against related FAD dependent aminoxidases. ORY-1001 is an enantiomerically pure KDM1A inhibitor with high selectivity against related FAD dependent aminoxidases. ORY-1001 does not inhibit non-related histone modifiers, and is clean in a CEREP diversity panel.
Cell Assay: ORY-1001 is an enantiomerically pure KDM1A inhibitor with high selectivity against related FAD dependent aminoxidases. ORY-1001 does not inhibit non-related histone modifiers, and is clean in a CEREP diversity panel. Treatment of THP-1 cells with ORY-1001, results in a time/dose dependent me2H3K4 accumulation at KDM1A target genes and concomitant induction of differentiation markers. |
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| ln Vivo |
| Daily oral administration of doses < 0.020 mg/kg leads to significantly reduced tumor growth in rodent xenografts. In vivo studies have shown that ORY-1001 presents excellent oral bioavailability, target exposure and activity in vivo. |
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| Animal Protocol |
| <0.020mg/kg, p.o. | | Rodent MV(4;11) xenografts | |
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| References |
J Clin Oncol. 2013, 31, suppl; abstr. e13543.
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Solubility Data
| Solubility (In Vitro) |
| DMSO: 5 mg/mL (16.5 mM) | | Water:61 mg/mL (201.1 mM) | | Ethanol:4 mg/mL warmed (13.2 mM) |
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| Solubility (In Vivo) |
| Chemical Name:(1r,4R)-N1-((1R,2S)-2-phenylcyclopropyl)cyclohexane-1,4-diamine dihydrochlorideInChi Key:UCINOBZMLCREGM-ISDLZHGDSA-NInChi Code:InChI=1S/C15H22N2.2ClH/c16-12-6-8-13(9-7-12)17-15-10-14(15)11-4-2-1-3-5-11;;/h1-5,12-15,17H,6-10,16H2;2*1H/t12-,13-,14-,15+;;/m0../s1SMILES Code:N[C@@H]1CC[C@@H](N[C@@H]2C[C@H]2C3=CC=CC=C3)CC1.[H]Cl.[H]Cl |
(Please use freshly prepared in vivo formulations for optimal results.)
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| Preparing Stock Solutions |
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1 mg |
5 mg |
10 mg |
| 1 mM |
3.2974 mL |
16.4870 mL |
32.9739 mL |
| 5 mM |
0.6595 mL |
3.2974 mL |
6.5948 mL |
| 10 mM |
0.3297 mL |
1.6487 mL |
3.2974 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. |
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