Iadademstat (ORY-1001; RG6016) 2HCl

Alias:

ORY1001; RG 6016;ORY-1001; RG-6016;ORY1001; RG6016; ORY1001 dihydrochloride, ORY1001 HCl; ORY1001 2HCl salt.

Cat No.:V0374 Purity: ≥98%

COA Product Data Instructions for use SDS

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.

Iadademstat (ORY-1001; RG6016) 2HCl Chemical Structure CAS No.: 1431326-61-2
Product category: Histone Demethylase

This product is for research use only, not for human use. We do not sell to patients.

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Citations by Top Journals: Nature, Cell, Science, etc.

Top Publications Citing lnvivochem Products

Nature 2024 Dec 18.

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nat Neurosci 2024, 27:1468-1474.

Nat Metab 2024, 6: 1108-1127.

Cell Stem Cell 2024, 31:106-126.e13.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2024,57:2651-2668.e12.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

NMR

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

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.

Biological Activity I Assay Protocols (From Reference)

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.

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.

Animal Protocol

<0.020mg/kg, p.o.

Rodent MV(4;11) xenografts

References

J Clin Oncol. 2013, 31, suppl; abstr. e13543.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula

C15H22N2.2HCL

Molecular Weight

303.27

Exact Mass

302.131

CAS #

1431326-61-2

Related CAS #

1431326-61-2 (2HCl) 1431303-72-8 (2HCl) 1431303-71-7 (xHCl) 1431304-21-0

PubChem CID

71664305

Appearance

Typically exists as solid at room temperature

Hydrogen Bond Donor Count

Hydrogen Bond Acceptor Count

Rotatable Bond Count

Heavy Atom Count

Complexity

239

Defined Atom Stereocenter Count

SMILES

N(C1CCC(CC1)N)[C@@H]1C[C@H]1C1C=CC=CC=1.Cl.Cl

InChi Key

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

Chemical Name

4-N-[(1R,2S)-2-phenylcyclopropyl]cyclohexane-1,4-diamine;dihydrochloride

Synonyms

ORY1001; RG 6016;ORY-1001; RG-6016;ORY1001; RG6016; ORY1001 dihydrochloride, ORY1001 HCl; ORY1001 2HCl salt.

HS Tariff Code

2934.99.9001

Storage

Powder -20°C 3 years

4°C 2 years

In solvent -80°C 6 months

-20°C 1 month

Shipping Condition

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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)

Solubility (In Vivo)

Chemical Name:(1r,4R)-N1-((1R,2S)-2-phenylcyclopropyl)cyclohexane-1,4-diamine dihydrochloride

InChi Key:UCINOBZMLCREGM-ISDLZHGDSA-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 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.)

Preparing Stock Solutions		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.

Calculator

Mass

Concentration

Volume

Molecular Weight*

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Concentration (Start)

Volume (Start)

Concentration (End)

Volume (End)

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

Total molecular weight

g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

Dosage mg/kg

Average weight of animals g

Dosing volume per animal μL

Number of animals

Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

% DMSO

% Tween 80

% ddH₂O

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.

Note： (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.

Clinical Trial Information

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT05420636	Recruiting	Drug: Iadademstat Drug: Paclitaxel	Small-cell Lung Cancer Neuroendocrine Carcinoma	Fox Chase Cancer Center	December 21, 2022	Phase 2
NCT05546580	Recruiting	Drug: Iadademstat Drug: Gilteritinib Oral Tablet	Acute Myeloid Leukemia, in Relapse Acute Myeloid Leukemia Refractory	Oryzon Genomics S.A.	November 14, 2022	Phase 1
NCT06357182	Not yet recruiting NEW	Drug: Azacitidine Procedure: Biospecimen Collection	Acute Myeloid Leukemia Myelodysplastic Syndrome/ Acute Myeloid Leukemia	OHSU Knight Cancer Institute	May 8, 2024	Phase 1
NCT06287775	Not yet recruiting	Biological: Atezolizumab Procedure: Biopsy	Extensive Stage Lung Small Cell Carcinoma Stage IV Lung Cancer AJCC v8	National Cancer Institute (NCI)	May 24, 2024	Phase 1 Phase 2

Biological Data

Morphologic response to treatment with iadademstat. (A) Representative images of blood smears showing morphologic differentiation from patient 28 (top) at screening (left) and cycle 1(C1), day 21 (D21) (right) and patient 31 (bottom) at screening (left) and C1D14 (right; two images from the same slide and patient are shown, separated by a dotted line). Charts show results of morphologic analysis of (B) blood smears and (C) bone marrow smears from selected MLL-translocated patients in the extension cohort (EC). HB, hemoglobin; WCC, white cell count; PLT, platelets.

Molecular response to treatment with iadademstat. Relative gene expression levels in nucleated blood cells of a differentiation biomarker panel in the extension cohort (EC). Magenta values show gene upregulation and pink values show gene downregulation. The maximum response and its timing within the treatment period is shown. Data are expressed as −ΔΔCp, calculated relative to expression of the endogenous gene HPRT1 and to the predose sample. Information on the occurrence of blast cell differentiation in bone marrow (BM) or blood and the percentage variation is also shown. The final column shows blast percentage in peripheral blood at baseline. (a) In bone marrow and/or peripheral blood. (b) Grey background indicates chromosome alterations involving MLL; dark grey, MLL fusion. (c) Between D5 and D12 of treatment (patient 28) or between D15 and D29 of treatment (patient 32). (d) Differentiation syndrome diagnosed. Morph. differ., morphologic differentiation.

Hematologic and biomarker response in patient 16. (A) Absolute neutrophil count (ANC) and platelet dynamics after treatment (cycle 1) and during the washout period in patient 16 of cohort V. Time course of changes in expression of differentiation biomarkers analyzed by quantitative reverse transcriptase–polymerase chain reaction shows that iadademstat induced expression of (B) CD86, (C) VCAN, (D) S100A12, and (E) LY96 in blood cells of patient 16.