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Histone Methytransferase

ORY-1001 (1431326-61-2)

ORY-1001 is a potent and selective inhibitor of LSD1 (IC₅₀ < 20 nM). It targets acute myeloid leukemia (AML) stem cells and significantly reduces tumor cell load while increasing survival time in mouse models of AML. ORY-1001 is in clinical trials for cancer treatment.

Not Intended for Therapeutic Use. For research use only.

CAS: 1431326-61-2 Category

ORY-1001 (1431326-61-2) Description:

ORY-1001 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 does not inhibit non-related histone modifiers. Treatment of THP-1 (MLL-AF9) cells with ORY-1001, results in a time/dose dependent me2H3K4 accumulation at KDM1A target genes and concomitant induction of differentiation markers (EC50 me2H3K4 and FACS CD11b <1nM). ORY-1001 induces apoptosis in THP-1 and inhibits proliferation and colony formation of MV(4;11) (MLL-AF4) cells (EC50 <1nM).

Lysine-specific demethylase 1 (LSD1) demethylates H3K4 and H3K9, resulting in transcriptional repression. It also controls the tumor suppressor activity of p53 by demethylating a specific p53 lysine residue (LYS370). ORY-1001 is an orally available, selective inhibitor of LSD1 (IC50 < 20 nM). It targets acute myeloid leukemia (AML) stem cells and significantly reduces tumor cell load while increasing survival time in mouse models of AML.3,4 ORY-1001 is in clinical trials for cancer treatment.

ORY-1001 (1431326-61-2) Specifications:

Product Name ORY-1001
Synonyms ORY-1001; 1431326-61-2; ORY-1001(trans); 1431303-72-8; ORY-1001 (RG-6016) 2HCl; ORY-1001(mixture of trans and cis isomers)
Chemical Name 4-N-[(1R,2S)-2-phenylcyclopropyl]cyclohexane-1,4-diamine;dihydrochloride
Drug Class Inhibitor
Purity >98%
CAS Number 1431326-61-2
Molecular Formula C15H24Cl2N2
Molecular Weight 303.271 g/mol
Monoisotopic Mass 302.132 g/mol
MDL number N/A
InChIKey UCINOBZMLCREGM-RNNUGBGQSA-N
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
SMILES C1CC(CCC1N)NC2CC2C3=CC=CC=C3.Cl.Cl
Form powder
Color white
Solubility  .DMSO (~7 mg/ml)
Storage Temp.  Dry, dark and at 0 – 4 C for short term (days to weeks) or -20 C for long term (months to years).
Shelf life >3 years if stored properly
Handling Protect from air and light
Application LSD1 Inhibitor

 


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RIDADR NONH for all modes of transport

References:

  • 1.Chemoprobe-based assays of histone lysine demethylase 1A target occupation enable in vivo pharmacokinetics and -dynamics studies of KDM1A inhibitors. Mascaró C, Ortega A, Carceller E, Ruiz Rodriguez R, Ciceri F, Lunardi S, Yu L, Hilbert M, Maes T. J Biol Chem. 2019 Feb 25. pii: jbc.RA118.006980. doi: 10.1074/jbc.RA118.006980. [Epub ahead of print]
  • 2.Targeting NOTCH activation in small cell lung cancer through LSD1 inhibition. Augert A, Eastwood E, Ibrahim AH, Wu N, Grunblatt E, Basom R, Liggitt D, Eaton KD, Martins R, Poirier JT, Rudin CM, Milletti F, Cheng WY, Mack F, MacPherson D. Sci Signal. 2019 Feb 5;12(567). pii: eaau2922. doi: 10.1126/scisignal.aau2922.
  • 3.ORY-1001 Suppresses Cell Growth and Induces Apoptosis in Lung Cancer Through Triggering HK2 Mediated Warburg Effect. Lu Z, Guo Y, Zhang X, Li J, Li L, Zhang S, Shan C. Front Pharmacol. 2018 Dec 4;9:1411. doi: 10.3389/fphar.2018.01411. eCollection 2018.
  • 4.ORY-1001: Overcoming the Differentiation Block in AML. Bose P, Konopleva MY. Cancer Cell. 2018 Mar 12;33(3):342-343. doi: 10.1016/j.ccell.2018.02.014.
  • 5.ORY-1001, a Potent and Selective Covalent KDM1A Inhibitor, for the Treatment of Acute Leukemia. Maes T, Mascaró C, Tirapu I, Estiarte A, Ciceri F, Lunardi S, Guibourt N, Perdones A, Lufino MMP, Somervaille TCP, Wiseman DH, Duy C, Melnick A, Willekens C, Ortega A, Martinell M, Valls N, Kurz G, Fyfe M, Castro-Palomino JC, Buesa C. Cancer Cell. 2018 Mar 12;33(3):495-511.e12. doi: 10.1016/j.ccell.2018.02.002. Epub 2018 Mar 1.