Valemetostat

SKU: orb1308963

Description

Valemetostat (DS-3201) is a dual EZH1 and EZH2 inhibitor for research into relapsed or refractory peripheral T-cell lymphoma (PTCL). Its application extends to preclinical in vitro and in vivo studies investigating epigenetic mechanisms in T-cell malignancies.

Research Area

Epigenetics & Chromatin

Key Properties

• CAS Number: 1809336-39-7
• MW: 488.02
• Purity: 99.83%
• Formula: C₂₆H₃₄ClN₃O₄
• SMILES: [H][C@@]1(CC[C@@H](CC1)N(C)C)[C@@]1(C)Oc2c(O1)c(C)c(cc2Cl)C(=O)NCc1c(C)cc(C)[nH]c1=O
• Target: Histone Methyltransferase
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:5 mg/mL (10.25 mM);DMSO:83.33 mg/mL (170.75 mM)

Bioactivity

• In Vivo:
  METHODS: In diffuse large B-cell lymphoma (DLBCL) cell xenograft model mice, Valemetostat (DS-3201) (25 mg/kg/50 mg/kg/100 mg/kg) was orally administered once a day to observe the tumor growth in the mice. RESULTS Valemetostat 100 mg/kg orally once daily was associated with nearly complete tumor regression without weight loss; lower doses (25 mg/kg) slowed tumor growth. METHODS: Primary MCL cells were transplanted into 6-week-old SCID-Beige (SCIDbg) mice (CB17.Cg-Prkdc) by subcutaneous injection, and the mice were treated with valemetostat 200 mg/kg twice daily for three days. week. RESULTS valemetostat treatment significantly inhibited tumor growth, and all valemetostat-treated mice survived to the end of the study period.
• In Vitro:
  METHODS: Valemetostat (DS-3201) was used to treat a group of malignant lymphoma cell lines derived from EZH1+ differentiated lymphocytes at low doses (0.1-100 nM), and the expression of H3K27me3 in sensitive lymphoma cells was observed. RESULTS valemetostat effectively inhibited H3K27me3 in sensitive lymphoma types, showing a targeted effect. METHODS: The EZH inhibitor valemetostat (0.1-1000nM) was chemically screened and derivatized using half the maximal inhibitory concentration (IC50) of EZH1/2 and cellular H3K27me3. RESULTS valemetostat strongly and specifically inhibits EZH1 and EZH2 (IC50 < 10 nM). METHODS: Human MCL cell lines Mino, JeKo-1, and REC-1 were treated with varying concentrations of valemetostat ranging from 3000 to 0.3 nmol/L or 3000 to 100 nmol/L, respectively. RESULTS Valemetostat at a concentration lower than 100 nmol/L significantly inhibited the growth of Mino and JeKo-1, while valemetostat at a concentration higher than 100 nmol/L inhibited the growth of REC-1.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

DS3201, DS-3201, DS 3201, lymphoma, inhibit, Inhibitor, HistoneMethyltransferase, Histone Methyltransferase, EZH1, EZH2, T-cell, Valemetostat

Compound Identifiers

PubChem CID

126481870