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Chemical Structure| 1431326-61-2 Chemical Structure| 1431326-61-2

Structure of ORY-1001
CAS No.: 1431326-61-2

Chemical Structure| 1431326-61-2

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ORY-1001 is a selective inhibitor of lysine-specific demethylase LSD1/KDM1A with IC50 of < 20 nM.

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Product Details of ORY-1001

CAS No. :1431326-61-2
Formula : C15H24Cl2N2
M.W : 303.27
SMILES Code : NC1CCC(N[C@H]2[C@H](C3=CC=CC=C3)C2)CC1.[H]Cl.[H]Cl
MDL No. :MFCD28900684
InChI Key :UCINOBZMLCREGM-RNNUGBGQSA-N
Pubchem ID :71664305

Safety of ORY-1001

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Related Pathways of ORY-1001

epigenetics

Isoform Comparison

Biological Activity

Target
  • KDM1

    LSD1, IC50:20 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
MV(4;11) cells 5 nM 96 hours The free KDM1A fraction was reduced by ~80% J Biol Chem. 2019 May 17;294(20):8311-8322.
THP-1 cells 25 nM Completely prevented pull-down of KDM1A J Biol Chem. 2019 May 17;294(20):8311-8322.
H1299 cells 80 and 160 µM 1, 2, 3, and 4 days ORY-1001 significantly inhibited cell proliferation Front Pharmacol. 2018 Dec 4;9:1411.
A549 cells 80 and 160 µM 1, 2, 3, and 4 days ORY-1001 significantly inhibited cell proliferation Front Pharmacol. 2018 Dec 4;9:1411.
BEAS-2B cells 80 and 160 µM 1, 2, 3, and 4 days ORY-1001 did not significantly affect normal cell proliferation Front Pharmacol. 2018 Dec 4;9:1411.
NCI-H510A 0.002 to 2000 nM 10 days Assessed the impact on cell viability, showing that ORY-1001 exhibited subnanomolar antiproliferative activity in NCI-H510A cells. ACS Pharmacol Transl Sci. 2021 Nov 12;4(6):1818-1834.
MV(4;11) 2000, 200, 20, and 2 nM 24 hours Assessed LSD1 target engagement, showing that ORY-1001 achieved high LSD1 target engagement at all concentrations tested. ACS Pharmacol Transl Sci. 2021 Nov 12;4(6):1818-1834.
A549 cells 50 nM 24 hours ORY-1001 inhibits KDM1A, leading to accumulation of H3K9 methylation and loss of H3K9 acetylation Epigenetics Chromatin. 2023 May 13;16(1):18.
U2OS cells 50 nM 24 hours ORY-1001 inhibits KDM1A, leading to accumulation of H3K9 methylation and loss of H3K9 acetylation Epigenetics Chromatin. 2023 May 13;16(1):18.
FHSC04 1 nM 48 hours ORY-1001 treatment led to changes in NOTCH1, REST, and ASCL1 transcription and protein expression, with increased cell death. Sci Signal. 2019 Feb 5;12(567):eaau2922.
BT-474 cells 10 µM 48 hours To evaluate the effect of iadademstat on SOX2 enhancer-driven transcriptional activation in BT-474 cells, results showed that iadademstat dose-dependently suppressed the transcriptional activation of SOX2 Aging (Albany NY). 2020 Mar 18;12(6):4794-4814.
MGC-803 5 µM 5 days Induced accumulation of H3K4me1/2 and H3K9me1/2, inhibited gastric cancer cell migration Front Pharmacol. 2021 Apr 15;12:640949.
BGC-823 5 µM 5 days Induced accumulation of H3K4me1/2 and H3K9me1/2, inhibited gastric cancer cell migration Front Pharmacol. 2021 Apr 15;12:640949.
MDA-MB-436 cells 3.98 µM (IC50) 6 days To evaluate the effect of iadademstat on mammosphere formation in MDA-MB-436 cells, results showed that iadademstat dose-dependently reduced the number of mammospheres Aging (Albany NY). 2020 Mar 18;12(6):4794-4814.
TF-1a 0.002 to 2000 nM 96 hours Assessed the impact on cell viability, showing that ORY-1001 exhibited subnanomolar antileukemic activity in TF-1a cells. ACS Pharmacol Transl Sci. 2021 Nov 12;4(6):1818-1834.
THP-1 0.02 to 2000 nM 96 hours Assessed the induction of CD11b protein levels, showing that ORY-1001 significantly induced CD11b expression in THP-1 cells. ACS Pharmacol Transl Sci. 2021 Nov 12;4(6):1818-1834.
NCI-H510A 10 nM 96 hours ORY-1001 treatment resulted in 1400 differentially expressed genes (FDR<0.05), with enrichment in NOTCH pathway genes and decreased expression of ASCL1. Sci Signal. 2019 Feb 5;12(567):eaau2922.

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
NSG mice SCLC PDX models Oral 400μg/kg Once weekly for 21 days ORY-1001 showed tumor inhibitory effects in all six of the ASCL1-positive PDX models tested, with complete and durable tumor regression observed in the FHSC04 model. Sci Signal. 2019 Feb 5;12(567):eaau2922.
C57BL/6 mice TC-1 subcutaneous xenograft model Intraperitoneal injection 50 mg/kg Three times per week for 3-4 weeks To evaluate the inhibitory effect of ORY-1001 combined with anti-CD47/PD-L1 monoclonal antibodies on tumor growth. The results showed that the combination of ORY-1001 and anti-CD47/PD-L1 monoclonal antibodies significantly inhibited tumor growth more effectively than a single blockade strategy. Cell Death Dis. 2021 Mar 17;12(4):282

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

3.30mL

0.66mL

0.33mL

16.49mL

3.30mL

1.65mL

32.97mL

6.59mL

3.30mL

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