Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C16H24N2 |
| Molecular Weight | 244.3752 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 4 / 4 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
N[C@H]1CC[C@H](CN[C@@H]2C[C@H]2C3=CC=CC=C3)CC1
InChI
InChIKey=VHNNYAVEBXCOSG-QCEMKRCNSA-N
InChI=1S/C16H24N2/c17-14-8-6-12(7-9-14)11-18-16-10-15(16)13-4-2-1-3-5-13/h1-5,12,14-16,18H,6-11,17H2/t12-,14-,15-,16+/m0/s1
| Molecular Formula | C16H24N2 |
| Molecular Weight | 244.3752 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 4 / 4 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
ORY-1001 (known as RG 6016) is a Lysine Specific Demethylase 1 (LSD1, also known as KDM1A) inhibitor (IC50 <20nM) with high selectivity against related FAD dependent aminoxidases (MAO-A/B, IL4I1, KDM1B >100uM, SMOX 7uM). LSD1 is a histone eraser enzyme that removes methyl groups, specifically mono and demethylated H3K4 and H3K9, and by doing so regulates the expression of many genes important in the onset and progression of diseases such as cancer and neurodegenerative disorders. ORY-1001 is a lead drug candidate of Oryzon Genomics S.A. under development for the treatment of acute myeloid leukemia (AML) – phase I/II and small cell lung cancer (SCLC) – phase I. Oryzon has made significant progress with ORY-1001 over the past years.
Approval Year
Doses
| Dose | Population | Adverse events |
|---|---|---|
220 ug/m2 1 times / day multiple, oral (unknown) MTD Dose: 220 ug/m2, 1 times / day Route: oral Route: multiple Dose: 220 ug/m2, 1 times / day Sources: |
unhealthy, ADULT n = 5 Health Status: unhealthy Condition: Leukemia, Myelocytic, acute Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 5 Sources: |
Other AEs: pneumonia, febrile neutropeni... Other AEs: pneumonia (grade 5, 1 pt) Sources: febrile neutropeni (grade 3, 1 pt) |
140 ug/m2 1 times / day multiple, oral (unknown) Recommended Dose: 140 ug/m2, 1 times / day Route: oral Route: multiple Dose: 140 ug/m2, 1 times / day Sources: |
unhealthy n = 14 Health Status: unhealthy Condition: Leukemia, Myelocytic, acute Sex: M+F Food Status: FASTED Population Size: 14 Sources: |
Disc. AE: thrombocytopenia... AEs leading to discontinuation/dose reduction: thrombocytopenia (grade 4, 1 pt) Sources: |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| febrile neutropeni | grade 3, 1 pt | 220 ug/m2 1 times / day multiple, oral (unknown) MTD Dose: 220 ug/m2, 1 times / day Route: oral Route: multiple Dose: 220 ug/m2, 1 times / day Sources: |
unhealthy, ADULT n = 5 Health Status: unhealthy Condition: Leukemia, Myelocytic, acute Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 5 Sources: |
| pneumonia | grade 5, 1 pt | 220 ug/m2 1 times / day multiple, oral (unknown) MTD Dose: 220 ug/m2, 1 times / day Route: oral Route: multiple Dose: 220 ug/m2, 1 times / day Sources: |
unhealthy, ADULT n = 5 Health Status: unhealthy Condition: Leukemia, Myelocytic, acute Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 5 Sources: |
| thrombocytopenia | grade 4, 1 pt Disc. AE |
140 ug/m2 1 times / day multiple, oral (unknown) Recommended Dose: 140 ug/m2, 1 times / day Route: oral Route: multiple Dose: 140 ug/m2, 1 times / day Sources: |
unhealthy n = 14 Health Status: unhealthy Condition: Leukemia, Myelocytic, acute Sex: M+F Food Status: FASTED Population Size: 14 Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no [IC50 >100 uM] |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no | ||||
| unlikely |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Sample Use Guides
in rodent xenografts: Daily oral administration of doses <0.020 mg/kg
Route of Administration:
Oral
ORY-1001 is a Lysine Specific Demethylase 1 (LSD1, also known as KDM1A) inhibitor (IC50 <20nM) with high selectivity against related FAD dependent aminoxidases (MAO-A/B, IL4I1, KDM1B >100uM, SMOX 7uM). 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). Microarray analysis of treated THP-1 cells reveals differentiation towards a monocyte-like phenotype. ORY-1001 induces apoptosis in THP-1 and inhibits proliferation and colony formation of MV(4;11) (MLL-AF4) cells (EC50 <1nM).
| Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 15:05:32 GMT 2023
by
admin
on
Sat Dec 16 15:05:32 GMT 2023
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| Record UNII |
XC0UT08SNJ
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| Record Status |
Validated (UNII)
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| Record Version |
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-
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66571534
Created by
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XC0UT08SNJ
Created by
admin on Sat Dec 16 15:05:32 GMT 2023 , Edited by admin on Sat Dec 16 15:05:32 GMT 2023
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1401966-39-9
Created by
admin on Sat Dec 16 15:05:32 GMT 2023 , Edited by admin on Sat Dec 16 15:05:32 GMT 2023
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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TARGET -> INHIBITOR |
IC50
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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ACTIVE MOIETY |
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![Structure of rel-trans-4-Amino-N-[(1R,2S)-2-phenylcyclopropyl]cyclohexanemethanamine](/img/bf7c4374-47c6-447e-a0ac-eb999265da0e.svg "Structure of rel-trans-4-Amino-N-[(1R,2S)-2-phenylcyclopropyl]cyclohexanemethanamine")