Abexinostat

SKU: orb1310623

Description

Abexinostat

Research Area

Epigenetics & Chromatin, Molecular Biology

Key Properties

• CAS Number: 783355-60-2
• MW: 397.42
• Purity: 98.39%
• Formula: C₂₁H₂₃N₃O₅
• SMILES: CN(C)Cc1c(oc2ccccc12)C(=O)NCCOc1ccc(cc1)C(=O)NO
• Target: HDAC
• Solubility: DMSO:4.1 mg/mL (10.32 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  HDAC1:7 nM(Ki)|HDAC2:19 nM (Ki)|MBLAC2:<10 nM (EC50)|HDAC8:280 nM (Ki)|HDAC6:17 nM (Ki)|HDAC3/SMRT:8.2 nM (Ki)|HDAC10:24 nM (Ki)
• In Vivo:
  In CHO cells, PCI-24781 is consistent with the inhibition of homologous recombination (HR), leading to a decreased capability of homology-directed repair induced by I-SceI-mediated chromosomal breaks. The compound exhibits significant antitumor activity across various cancer cell lines, with GI50 values ranging from 0.15 μM to 3.09 μM. Treatment with PCI-24781 results in dose-dependent accumulation of acetylated histones/microtubule proteins, induction of PARP cleavage, p21 expression, and γH2AX accumulation in HCT116 and DLD-1 cell lines. PCI-24781 induces apoptosis in soft tissue cells, causes a deficiency in S phase, and arrests the cell cycle at the G2 phase. In STS cells, the compound likely induces transcriptional repression of Rad51 by enhancing E2F1 binding to the proximal promoter region of Rad51. Additionally, PCI-24781 prompts caspase and reactive oxygen species-dependent NF-κB-signaling-mediated apoptosis in non-Hodgkin's lymphoma and Hodgkin's lymphoma. PCI-24781 also inhibits the proliferation of human umbilical vein endothelial cells with a GI50 of 0.43 μM. Furthermore, it suppresses HDAC enzyme activity, leading to a noticeable decrease in transcription levels of HR-related genes, including RAD51.
• In Vitro:
  HCT116 xenograft mice were treated with PCI-24781 for four consecutive days each week, followed by a three-day drug holiday, at dosages of 20, 40, 80, and 160 mg/kg, achieving inhibition rates of 48%, 57%, 82.2%, and 80.0%, respectively. Alternate-day treatment with 200 mg/kg PCI-24781 significantly inhibited the growth of both HCT116 and DLD-1 tumor cells, with inhibition rates of 69% and 59%, respectively.
• Cell Research:
  Cells are cultured for at least two doubling times, and growth is monitored at the end of PCI-24781 exposure using an Alamar blue fluorometric cell proliferation assay. PCI-24781 is assayed in triplicate wells in 96-well plates at nine concentrations using half-log intervals ranging from 0.0015 μM to 10 μM. The final DMSO concentration in each well is 0.15%. The concentration required to inhibit cell growth by 50% (GI50) and 95% confidence intervals are estimated from nonlinear regression using a four-parameter logistic equation.(Only for Reference)

Storage & Handling

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

Alternative Names

inhibit, PCI 24781, PCI24781, PCI-24781, HDAC, HDAC6, HDAC3/SMRT, HDAC2, HDAC10, HDAC1, Inhibitor, MBLAC2, Histone deacetylases, CRA024781, CRA-024781, CRA24781, CRA-24781, CRA 024781, CRA 24781, Abexinostat, antitumor activity

Compound Identifiers

PubChem CID

11749858