H3B-8800

SKU: orb1962246

Description

H3B-8800 is a small molecule modulator of SF3B1, a splicing factor. It serves as a research tool for investigating the underlying mechanisms of transfusion-dependent anemias, such as myelodysplastic syndromes, in both cellular and animal models.

Research Area

Cell Biology

Key Properties

• CAS Number: 1825302-42-8
• MW: 555.71
• Purity: 98.31%
• Formula: C₃₁H₄₅N₃O₆
• SMILES: O(C(=O)N1CCN(C)CC1)[C@H]2/C=C/[C@H](C)[C@@H](\C(=C\C=C\[C@@H](C)C3=CC=CC=N3)\C)OC(=O)C[C@H](O)CC[C@@]2(C)O
• Target: Apoptosis,Others
• Solubility: DMSO:122.5 mg/mL (220.44 mM)

Bioactivity

• Target IC50:
  missense hotspot mutants R175H:8.3 nM|missense hotspot mutants R273H:3.2 nM|missense hotspot mutants R248H:16.3 nM|KPFLC cells (overexpressing human WT):26.5 nM|Panc05.04 cells:13 nM|SF3B1:0.3-2 nM
• In Vivo:
  We conducted a Phase I clinical trial of H3B-8800, an oral small molecule compound that binds splicing factor 3B1 (SF3B1), in patients with MDS, CMML or AML. Of the 84 patients enrolled in the trial (42 MDS, 4 CMML and 38 AML), 62 were dependent on red blood cell (RBC) transfusions at enrollment. The dose-escalation cohort examined two once-daily dosing regimens: regimen I (5 days on/9 days off, study dose range 1-40 mg, n=65) and regimen II (21 days on/7 days off, 7-20 mg, n=19); 27 patients were treated for ≥180 days. The most common treatment-related emergent adverse events included diarrhea, nausea, fatigue, and vomiting. No complete or partial responses meeting IWG criteria were observed; however, RBC transfusion free intervals of more than 56 days were observed in nine patients who were transfusion dependent at enrollment (15%). Five of 15 MDS patients with missense SF3B1 mutations experienced RBC transfusion independence (TI). Increased expression of the pre-treatment target of splicing transmembrane protein 14C (TMEM14C) was observed in MDS patients experiencing RBC TI.

Storage & Handling

• Storage: store at low temperature | 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

SF3B1, H3B 8800, H3B8800, H3B-8800

Compound Identifiers

PubChem CID

92135969