T-3775440 hydrochloride

CAS No. 1422535-52-1

T-3775440 hydrochloride( T 3775440 | T3775440 )

Catalog No. M11774 CAS No. 1422535-52-1

A novel potent, selecitve, irreversible LSD1 inhibitor with IC50 of 2.1 nM.

Purity : >98% (HPLC)

COA Datasheet HNMR HPLC MSDS Handing Instructions
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5MG 237 Get Quote
10MG 354 Get Quote
25MG 592 Get Quote
50MG 843 Get Quote
100MG 1143 Get Quote
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Biological Information

  • Product Name
    T-3775440 hydrochloride
  • Note
    Research use only, not for human use.
  • Brief Description
    A novel potent, selecitve, irreversible LSD1 inhibitor with IC50 of 2.1 nM.
  • Description
    A novel potent, selecitve, irreversible LSD1 inhibitor with IC50 of 2.1 nM; displays high selectivity for LSD1 relative to other monoamine oxidases (e.g., MAO-A and MAO-B); disrupts the interaction between LSD1 and growth factor-independent 1B (GFI1B) in leukemia cell lines, exhibites significant antitumor efficacy in AEL and AMKL xenograft models.
  • In Vitro
    T-3775440 demonstrates irreversible inhibition of recombinant human LSD1, with a kinact/KI value of 1.7×105 (sec?1 M?1). T-3775440 is highly selective for LSD1 relative to other monoamine oxidases (e.g., MAO-A and MAO-B), with an IC50 value of 2.1 nM). T-3775440 blocks the proliferation of several cell lines as quickly as day 3 of treatment. Notably, the granulocyte/macrophage markers CD86 and CD11b are commonly upregulated on both TF-1a and HEL92.1.7 cells in response to T-3775440 treatment, whereas the erythroid markers CD235a and CD71 are downregulated by this treatment. In CMK11-5 cells, CD86 mRNA expression is also clearly upregulated by T-3775440 in a concentration-dependent manner, although only a modest increase in cell surface CD86 expression is observed. T-3775440 treatment disrupts the LSD1-GFI1B association in a concentration-dependent manner. T-3775440 decreases LSD1 binding but not GFI1B binding and increases the level of dimethylated H3K4 at the PI16 locus.
  • In Vivo
    T-3775440 upregulates CD86 mRNA expression in tumor xenografts of HEL92.1.7 cells in a dose-dependent manner following the oral administration of single doses ranging from 3 to 30 mg/kg. To investigate target engagement of this compound in tumors, PI16 expression levels is tested as a direct biomarker. As expected, PI16 suppression is dramatically reversed by T-3775440 treatment. In a TF-1a (AEL) tumor xenograft model, T-3775440 exhibits significant antitumor effects, with 15-day T/C values of 15.6% and <0% at doses of 20 and 40 mg/kg, respectively. T-3775440 also exhibits potent antitumor effects in an additional AEL model of HEL 92.1.7 and an AMKL model of CMK11-5, leading to nearly complete tumor growth suppression during the dosing period. It is found that in mice, T-3775440 treatment results in a transient reduction in platelets, followed by a significant rebound; this is considered a mechanism-based adverse effect of LSD1 inhibition. On a dosing schedule comprising 5 days on/2 days off, a statistically significant difference in body weight is observed between vehicle- and T-3775440–treated tumor xenograft model mice at higher doses. However, efficacious T-3775440 doses are tolerated in all subcutaneous tumor xenograft models.
  • Synonyms
    T 3775440 | T3775440
  • Pathway
    Chromatin/Epigenetic
  • Target
    Histone Demethylase
  • Recptor
    Histone Demethylase
  • Research Area
    Cancer
  • Indication
    ——

Chemical Information

  • CAS Number
    1422535-52-1
  • Formula Weight
    346.859
  • Molecular Formula
    C18H23ClN4O
  • Purity
    >98% (HPLC)
  • Solubility
    DMSO : ≥ 30.18 mg/mL 87.01 mM
  • SMILES
    CN1C=C(C=N1)C(=O)NC2=CC=C(C=C2)C3CC3NCC4CC4.Cl
  • Chemical Name
    N-(4-((1S,2R)-2-((cyclopropylmethyl)amino)cyclopropyl)phenyl)-1-methyl-1H-pyrazole-4-carboxamide hydrochloride

Shipping & Storage Information

  • Storage
    (-20℃)
  • Shipping
    With Ice Pack
  • Stability
    ≥ 2 years

Reference

1. Takagi S, et al. Cancer Res. 2017 Jun 30. pii: canres.3502.2016. 2. Ishikawa Y, et al. Mol Cancer Ther. 2017 Feb;16(2):273-284.
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