Ladademstat free base | CAS#1431326-61-2 | LSD1 inhibitor

MedKoo Cat#: 527485 | Name: Ladademstat free base

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Ladademstat, also known as ORY1001 and RG-6016, is 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). ORY-1001 induces apoptosis in THP-1 and inhibits proliferation and colony formation of MV(4;11) (MLL-AF4) cells (EC50 <1nM).

Chemical Structure

Ladademstat free base

CAS#1431304-21-0 (free base)

Theoretical Analysis

MedKoo Cat#: 527485

Name: Ladademstat free base

CAS#: 1431304-21-0 (free base)

Chemical Formula: C15H22N2

Exact Mass: 230.1783

Molecular Weight: 230.36

Elemental Analysis: C, 78.21; H, 9.63; N, 12.16

Price and Availability

Size	Price	Availability
5mg	USD 295.00	2 Weeks
10mg	USD 485.00	2 Weeks
25mg	USD 865.00	2 Weeks
50mg	USD 1,305.00	2 Weeks
100mg	USD 2,250.00	2 Weeks

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Related CAS #

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

Synonym

ORY-1001; ORY1001; ORY 1001; RG6016; RG 6016; RG-6016; Iadademstat

IUPAC/Chemical Name

N-[(1R,2S)-2-Phenylcyclopropyl]-1,4-cyclohexanediamine

InChi Key

NC1CCC(N[C@H]2[C@H](C3=CC=CC=C3)C2)CC1

InChi Code

InChI=1S/C15H22N2/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/t12?,13?,14-,15+/m0/s1

SMILES Code

NC1CCC(N[C@H]2[C@H](C3=CC=CC=C3)C2)CC1

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

ORY1001, also known as RG-6016, is a KDM1A inhibitor (IC50 <20nM).

In vitro activity:

Results indicated that ORY-1001 treatment restrained the proliferation while enhanced the apoptosis of BC cells, accompanied by the change of proliferation- and apoptosis-related proteins expression. Furthermore, ORY-1001 reduced the level of AR in BC cells. After the activation of AR by R1881, the decreased proliferation and enhanced apoptosis of BC cells triggered by ORY-1001 intervention were partially abolished. Reference: Drug Dev Res. 2022 Feb;83(1):208-216. https://pubmed.ncbi.nlm.nih.gov/34347904/

In vivo activity:

This study examined the effect of LSD1 inhibitor ORY-1001 on the development of renal fibrosis in murine kidneys after 10 days of sham operation and ureteral ureter ligation by Masson’s Trichrome and Picrosirius Red staining. Administration of ORY-1001 reduced the protein level of the upregulated LSD1 (Figure 1E) but not the mRNA level of LSD1 (Figure S1A), increased the mono- and di-methylation of H3K4, and decreased the expression of fibronectin and α-SMA in UUO-injured kidneys compared to those in vehicle-treated UUO kidneys (Figures 1E and S1B,C). Immunofluorescence staining also showed a dramatic increase in the expression of renal LSD1 and α-SMA in UUO injured kidneys, whereas administration of ORY-1001 decreased both LSD1 and α-SMA in UUO-injured kidneys (Figure 1F). These results suggest that LSD1 plays a critical role in the regulation of renal fibrosis development and ORY-1001 may be an antifibrotic agent. Reference: FASEB J. 2022 Jan;36(1):e22122. https://pubmed.ncbi.nlm.nih.gov/34958158/

Preparing Stock Solutions

The following data is based on the product molecular weight 230.36 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Wang T, Zhang F, Sun F. ORY-1001, a KDM1A inhibitor, inhibits proliferation, and promotes apoptosis of triple negative breast cancer cells by inactivating androgen receptor. Drug Dev Res. 2022 Feb;83(1):208-216. doi: 10.1002/ddr.21860. Epub 2021 Aug 4. PMID: 34347904. 2. Lu Z, Guo Y, Zhang X, Li J, Li L, Zhang S, Shan C. ORY-1001 Suppresses Cell Growth and Induces Apoptosis in Lung Cancer Through Triggering HK2 Mediated Warburg Effect. Front Pharmacol. 2018 Dec 4;9:1411. doi: 10.3389/fphar.2018.01411. PMID: 30568590; PMCID: PMC6290890. 3. Zhang X, Li LX, Yu C, Nath KA, Zhuang S, Li X. Targeting lysine-specific demethylase 1A inhibits renal epithelial-mesenchymal transition and attenuates renal fibrosis. FASEB J. 2022 Jan;36(1):e22122. doi: 10.1096/fj.202101566R. PMID: 34958158; PMCID: PMC9154004. 4. Lorenzo PI, Martin Vazquez E, López-Noriega L, Fuente-Martín E, Mellado-Gil JM, Franco JM, Cobo-Vuilleumier N, Guerrero Martínez JA, Romero-Zerbo SY, Perez-Cabello JA, Rivero Canalejo S, Campos-Caro A, Lachaud CC, Crespo Barreda A, Aguilar-Diosdado M, García Fuentes E, Martin-Montalvo A, Álvarez Dolado M, Martin F, Rojo-Martinez G, Pozo D, Bérmudez-Silva FJ, Comaills V, Reyes JC, Gauthier BR. The metabesity factor HMG20A potentiates astrocyte survival and reactive astrogliosis preserving neuronal integrity. Theranostics. 2021 May 12;11(14):6983-7004. doi: 10.7150/thno.57237. PMID: 34093866; PMCID: PMC8171100.

In vitro protocol:

In vivo protocol:

1. Zhang X, Li LX, Yu C, Nath KA, Zhuang S, Li X. Targeting lysine-specific demethylase 1A inhibits renal epithelial-mesenchymal transition and attenuates renal fibrosis. FASEB J. 2022 Jan;36(1):e22122. doi: 10.1096/fj.202101566R. PMID: 34958158; PMCID: PMC9154004. 2. Lorenzo PI, Martin Vazquez E, López-Noriega L, Fuente-Martín E, Mellado-Gil JM, Franco JM, Cobo-Vuilleumier N, Guerrero Martínez JA, Romero-Zerbo SY, Perez-Cabello JA, Rivero Canalejo S, Campos-Caro A, Lachaud CC, Crespo Barreda A, Aguilar-Diosdado M, García Fuentes E, Martin-Montalvo A, Álvarez Dolado M, Martin F, Rojo-Martinez G, Pozo D, Bérmudez-Silva FJ, Comaills V, Reyes JC, Gauthier BR. The metabesity factor HMG20A potentiates astrocyte survival and reactive astrogliosis preserving neuronal integrity. Theranostics. 2021 May 12;11(14):6983-7004. doi: 10.7150/thno.57237. PMID: 34093866; PMCID: PMC8171100.

1: Li HX, Yang LY, Wan YX, Zhao YP, Liu YF, Wen KS, Yang JJ, Fan XY. The epigenetically regulated PP1α expression by KDM1A may contribute to oxycodone conditioned place preference in mice. Biomed Pharmacother. 2024 Jul;176:116931. doi: 10.1016/j.biopha.2024.116931. Epub 2024 Jun 12. PMID: 38870630. 2: Senanayaka D, Zeng D, Deniz E, Priyankara IK, Helmbreck J, Schneider O, Mardikar A, Uren A, Reiter NJ. Anticancer Drugs of Lysine Specific Histone Demethylase-1 (LSD1) Display Variable Inhibition on Nucleosome Substrates. Biochemistry. 2024 Jun 4;63(11):1369-1375. doi: 10.1021/acs.biochem.4c00090. Epub 2024 May 14. PMID: 38742921. 3: Shen L, Wang B, Wang SP, Ji SK, Fu MJ, Wang SW, Hou WQ, Dai XJ, Liu HM. Combination Therapy and Dual-Target Inhibitors Based on LSD1: New Emerging Tools in Cancer Therapy. J Med Chem. 2024 Jan 25;67(2):922-951. doi: 10.1021/acs.jmedchem.3c02133. Epub 2024 Jan 12. PMID: 38214982. 4: Yuan J, Que R, Zhao W, Song F, Cao Y, Yu B. Influences of lysine-specific demethylase 1 inhibitors on NO synthase-Kruppel-like factor pathways in human endothelial cells in vitro and zebrafish (Danio rerio) larvae in vivo. J Appl Toxicol. 2023 Nov;43(11):1748-1760. doi: 10.1002/jat.4512. Epub 2023 Jul 5. PMID: 37408164. 5: Monte-Serrano E, Morejón-García P, Campillo-Marcos I, Campos-Díaz A, Navarro- Carrasco E, Lazo PA. The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase. Epigenetics Chromatin. 2023 May 13;16(1):18. doi: 10.1186/s13072-023-00494-7. PMID: 37179361; PMCID: PMC10182654. 6: Zhang C, Wang Z, Shi Y, Yu B, Song Y. Recent advances of LSD1/KDM1A inhibitors for disease therapy. Bioorg Chem. 2023 May;134:106443. doi: 10.1016/j.bioorg.2023.106443. Epub 2023 Feb 24. PMID: 36857932. 7: Noce B, Di Bello E, Fioravanti R, Mai A. LSD1 inhibitors for cancer treatment: Focus on multi-target agents and compounds in clinical trials. Front Pharmacol. 2023 Feb 2;14:1120911. doi: 10.3389/fphar.2023.1120911. PMID: 36817147; PMCID: PMC9932783. 8: Sacilotto N, Dessanti P, Lufino MMP, Ortega A, Rodríguez-Gimeno A, Salas J, Maes T, Buesa C, Mascaró C, Soliva R. Comprehensive in Vitro Characterization of the LSD1 Small Molecule Inhibitor Class in Oncology. ACS Pharmacol Transl Sci. 2021 Nov 12;4(6):1818-1834. doi: 10.1021/acsptsci.1c00223. PMID: 34927013; PMCID: PMC8669716. 9: Zhai Y, Wang J, Lang T, Kong Y, Rong R, Cai Y, Ran W, Xiong F, Zheng C, Wang Y, Yu Y, Zhu HH, Zhang P, Li Y. T lymphocyte membrane-decorated epigenetic nanoinducer of interferons for cancer immunotherapy. Nat Nanotechnol. 2021 Nov;16(11):1271-1280. doi: 10.1038/s41565-021-00972-7. Epub 2021 Sep 27. PMID: 34580467. 10: Wang T, Zhang F, Sun F. ORY-1001, a KDM1A inhibitor, inhibits proliferation, and promotes apoptosis of triple negative breast cancer cells by inactivating androgen receptor. Drug Dev Res. 2022 Feb;83(1):208-216. doi: 10.1002/ddr.21860. Epub 2021 Aug 4. PMID: 34347904. 11: Wang Y, Xie Q, Tan H, Liao M, Zhu S, Zheng LL, Huang H, Liu B. Targeting cancer epigenetic pathways with small-molecule compounds: Therapeutic efficacy and combination therapies. Pharmacol Res. 2021 Nov;173:105702. doi: 10.1016/j.phrs.2021.105702. Epub 2021 Jun 5. PMID: 34102228. 12: Duan YC, Jin LF, Ren HM, Zhang SJ, Liu YJ, Xu YT, He ZH, Song Y, Yuan H, Chen SH, Guan YY. Design, synthesis, and biological evaluation of novel dual inhibitors targeting lysine specific demethylase 1 (LSD1) and histone deacetylases (HDAC) for treatment of gastric cancer. Eur J Med Chem. 2021 Aug 5;220:113453. doi: 10.1016/j.ejmech.2021.113453. Epub 2021 Apr 25. PMID: 33957387. 13: Ma P, Jia G, Song Z. Monobenzone, a Novel and Potent KDM1A Inhibitor, Suppresses Migration of Gastric Cancer Cells. Front Pharmacol. 2021 Apr 15;12:640949. doi: 10.3389/fphar.2021.640949. PMID: 33935733; PMCID: PMC8084583. 14: Xu S, Wang X, Yang Y, Li Y, Wu S. LSD1 silencing contributes to enhanced efficacy of anti-CD47/PD-L1 immunotherapy in cervical cancer. Cell Death Dis. 2021 Mar 17;12(4):282. doi: 10.1038/s41419-021-03556-4. PMID: 33731702; PMCID: PMC7969769. 15: Zhang S, Liu M, Yao Y, Yu B, Liu H. Targeting LSD1 for acute myeloid leukemia (AML) treatment. Pharmacol Res. 2021 Feb;164:105335. doi: 10.1016/j.phrs.2020.105335. Epub 2020 Dec 4. PMID: 33285227. 16: Salamero O, Montesinos P, Willekens C, Pérez-Simón JA, Pigneux A, Récher C, Popat R, Carpio C, Molinero C, Mascaró C, Vila J, Arévalo MI, Maes T, Buesa C, Bosch F, Somervaille TCP. First-in-Human Phase I Study of Iadademstat (ORY-1001): A First-in-Class Lysine-Specific Histone Demethylase 1A Inhibitor, in Relapsed or Refractory Acute Myeloid Leukemia. J Clin Oncol. 2020 Dec 20;38(36):4260-4273. doi: 10.1200/JCO.19.03250. Epub 2020 Oct 14. PMID: 33052756; PMCID: PMC7768337. 17: Dai XJ, Liu Y, Xiong XP, Xue LP, Zheng YC, Liu HM. Tranylcypromine Based Lysine-Specific Demethylase 1 Inhibitor: Summary and Perspective. J Med Chem. 2020 Dec 10;63(23):14197-14215. doi: 10.1021/acs.jmedchem.0c00919. Epub 2020 Sep 30. Erratum in: J Med Chem. 2021 May 13;64(9):6412. doi: 10.1021/acs.jmedchem.1c00570. PMID: 32931269. 18: Chen K, Cai Y, Cheng C, Zhang J, Lv F, Xu G, Duan P, Wu Y, Wu Z. MYT1 attenuates neuroblastoma cell differentiation by interacting with the LSD1/CoREST complex. Oncogene. 2020 May;39(21):4212-4226. doi: 10.1038/s41388-020-1268-6. Epub 2020 Apr 6. PMID: 32251364. 19: Cuyàs E, Gumuzio J, Verdura S, Brunet J, Bosch-Barrera J, Martin-Castillo B, Alarcón T, Encinar JA, Martin ÁG, Menendez JA. The LSD1 inhibitor iadademstat (ORY-1001) targets SOX2-driven breast cancer stem cells: a potential epigenetic therapy in luminal-B and HER2-positive breast cancer subtypes. Aging (Albany NY). 2020 Mar 18;12(6):4794-4814. doi: 10.18632/aging.102887. Epub 2020 Mar 18. PMID: 32191225; PMCID: PMC7138538. 20: Fang Y, Liao G, Yu B. LSD1/KDM1A inhibitors in clinical trials: advances and prospects. J Hematol Oncol. 2019 Dec 4;12(1):129. doi: 10.1186/s13045-019-0811-9. PMID: 31801559; PMCID: PMC6894138.