Lenalidomide hemihydrate

SKU: orb1305779

Description

Lenalidomide hemihydrate is an oral immunomodulatory agent derived from thalidomide. It functions by binding to cereblon (CRBN), the substrate receptor of the CRL4 ubiquitin ligase complex, leading to the targeted ubiquitination and degradation of the transcription factors IKZF1 and IKZF3. This mechanism underpins its extensive use in research for hematological malignancies and immunology, both in vitro and in vivo.

Research Area

Cell Biology, Immunology & Inflammation, Pharmacology & Drug Discovery

Key Properties

• CAS Number: 847871-99-2
• MW: 268.28
• Purity: 100.00%
• Formula: C₁₃H₁₃N₃O₃.1/2H₂O
• SMILES: O=C(C(N(CC1=C2C=CC=C1N)C2=O)CC3)NC3=O.O=C(C(N(CC4=C5C=CC=C4N)C5=O)CC6)NC6=O.[H]O[H]
• Target: Molecular Glues,IKZF,TNF,Apoptosis,Ligands for E3 Ligase
• Solubility: DMSO:Soluble

Bioactivity

• Target IC50:
  TNF-α:13 nM
• In Vivo:
  Range finding studies used lenalidomide concentrations up to 15 mg/kg IV, 22.5 mg/kg intraperitoneal injections (IP), and 45 mg/kg oral gavage (PO). Pharmacokinetic studies evaluated doses of 0.5, 1.5, 5, and 10 mg/kg IV and 0.5 and 10 mg/kg doses for IP and oral routes. Liquid chromatography-tandem mass spectrometry was used to quantify lenalidomide in plasma, brain, lung, liver, heart, kidney, spleen, and muscle. Pharmacokinetic parameters were estimated using noncompartmental and compartmental methods. Doses of 15 mg/kg IV, 22.5 mg/kg IP, and 45 mg/kg PO lenalidomide caused no observable toxicity up to 24 h postdose. We observed dose-dependent kinetics over the evaluated dosing range. Administration of 0.5 and 10 mg/kg resulted in systemic bioavailability ranges of 90-105% and 60-75% via IP and oral routes, respectively. Lenalidomide was detectable in the brain only after IV dosing of 5 and 10 mg/kg. Dose-dependent distribution was also observed in some tissues. High oral bioavailability of lenalidomide in mice is consistent with oral bioavailability in humans. Atypical lenalidomide tissue distribution was observed in spleen and brain.
• In Vitro:
  Lenalidomide inhibited autoubiquitination of CRBN in HEK293T cells expressing thalidomide-binding competent wild-type CRBN, but not thalidomide-binding defective CRBN(YW/AA). Overexpression of CRBN wild-type protein, but not CRBN(YW/AA) mutant protein, in KMS12 myeloma cells, amplified pomalidomide-mediated reductions in c-myc and IRF4 expression and increases in p21(WAF-1) expression. Long-term selection for lenalidomide resistance in H929 myeloma cell lines was accompanied by a reduction in CRBN, while in DF15R myeloma cells resistant to lenalidomide, CRBN protein was undetectable.

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

cereblon, Cereblon, CC-5013 hemihydrate, degradation, CRL4, Apoptosis, analog, ligand, LigandforE3Ligase, Ligand for E3 Ligase, ligase, Ligands for E3 Ligase, inhibit, myeloma, multiple, immunomodulatory, Molecular Glues, MolecularGlues, Inhibitor, IKZF1, IKZF3, Lenalidomide, Lenalidomide Hemihydrate, Lenalidomide hemihydrate, E3 ligase-recruiting Moiety, TNF-α

Compound Identifiers

PubChem CID

46220375