1423715-09-6 Usage
Description
SP2509 (1423715-09-6) is a potent (IC50 = 13 nM) and reversible inhibitor of the histone demethylase LSD1 (KDM1A).1 It is inactive against the closely related flavin enzymes MAO A,B as well as lactate dehydrogenase, several CYP’s and hERG. LSD1 regulates the balance between self-renewal and differentiation of stem cells and is highly expressed in various cancers.2-6 SP2509 promotes autophagy in neuroblastoma cells.7
Uses
SP 2509 reduces the effect of the LSD1 binding to CoREST, resulting in increased methylation of H3K4 and driving increased expression of p21, p27 and CCAAT/enhancer binding protein α in acute myeloid leukemia cells. Anti-leukemia agent.
General Description
A cell-permeable, lysine-specific demethylase 1 (LSD1) active site-targeting phenethylidene-benzohydrazide that inhibits LSD1 activity (IC50 = 13 nM) in a reversible and substrate non-competitive (Ki = 34 nM) manner, while inhibiting CYP3A4 only at much higher concentrations (IC50 = 2.61 μM) and displaying little or no potency towards CYP1A2/2C9/2C19/2D6. MAO-A/B, D-lactate dehydrogenase, glucose oxidase, and hERG (IC50 ≥8.0 μM). Shown to enhance histone H3 Lys9 dimethylation (H3K9me2) in androgen-dependent prostate cancer VCaP cultures (1 to 10 μM) and effectively inhibits LSD1-dependent cancer growth (IC50 in nM = 329/SK-N-MC, 356/AN3 Ca, 429/HT29, 468/MIA PaCa-2, 489/BT-20, 612/HER218, 614/HCT 116, 637/MCF-7, 649/T-47D; 96 h).
Biochem/physiol Actions
Cell permeable: yes
References
1) Sorna, et al. (2013), High-Throughput Virtual Screening Identifies Novel N’-(1-Phenylethylidene)-benzohydrazides as Potent, Specific, and Reversible LSD1 Inhibitors; J. Med. Chem. 56 9496
2) Hosseini and Minucci (2017) A comprehensive review of lysine-specific demethylase 1 and its roles in cancer; Epigenomics 9 1123
3) Fiskus et al. (2014), Highly effective combination of LSD1 (KDM1A) antagonist and pan-histone deacetylase inhibitor against human AML cells; Leukemia 28 2155
4) Wen et al. (2018), Novel combination of histone methylation modulators with therapeutic synergy against acute myeloid leukemia in vitro and in vivo; Cancer Lett. 413 35
5) Tsai et al. (2018), Stress-induced phosphoprotein 1 acts as a scaffold protein for glycogen synthase kinase-3 beta-mediated phosphorylation of lysine-specific demethylase 1; Oncogenesis 7 31
6) Lu et al. (2018), Hypoxia Promotes Resistance to EGFR Inhibition in NSCLC Cells via the Histone Demethylases LSD1 and PLU-1; Mol. Cancer Epub ahead of print June 22, 2018
7) Ambrosio et al. (2017), Lysine-specific demethylase LSD1 regulates autophagy in neuroblastoma through SESN2-dependent pathway; Oncogene 36 36701
Check Digit Verification of cas no
The CAS Registry Mumber 1423715-09-6 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,4,2,3,7,1 and 5 respectively; the second part has 2 digits, 0 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 1423715-09:
(9*1)+(8*4)+(7*2)+(6*3)+(5*7)+(4*1)+(3*5)+(2*0)+(1*9)=136
136 % 10 = 6
So 1423715-09-6 is a valid CAS Registry Number.
1423715-09-6Relevant articles and documents
High-throughput virtual screening identifies novel N ′-(1- phenylethylidene)-benzohydrazides as potent, specific, and reversible LSD1 inhibitors
Sorna, Venkataswamy,Theisen, Emily R.,Stephens, Bret,Warner, Steven L.,Bearss, David J.,Vankayalapati, Hariprasad,Sharma, Sunil
, p. 9496 - 9508 (2014/01/06)
Lysine specific demethylase 1 (LSD1) plays an important role in regulating histone lysine methylation at residues K4 and K9 on histone H3 and is an attractive therapeutic target in multiple malignancies. Here we report a structure-based virtual screen of
