(E/Z)-Zotiraciclib

SKU: orb1306326

Description

(E/Z)-Zotiraciclib

Research Area

Cardiovascular Research, Cell Biology, Epigenetics & Chromatin, Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 937270-47-8
• MW: 372.46
• Purity: 99.92%
• Formula: C₂₃H₂₄N₄O
• SMILES: CN1CC2=CC(N=C3NC(C=4C=C(C=CC4)OCCC=CC1)=CC=N3)=CC=C2
• Target: CDK,JAK,FLT
• Solubility: 10% DMSO+40% PEG300+5% Tween-80+45% Saline:1 mg/mL (2.68 mM);DMSO:20 mg/mL (53.7 mM)

Bioactivity

• Target IC50:
  FLT3:56 nM|JAK2:73 nM|CDK2:13 nM
• In Vivo:
  Treatment with (E/Z)-Zotiraciclib (75 mg/kg p.o. q.d. 3×/week) significantly inhibits the growth of tumors with a mean TGI of 82%, while the lower dose(50 mg/kg p.o. 3×/week) is marginally effective. Treatment with (E/Z)-Zotiraciclib using either regime significantly inhibits the growth of tumors with mean TGIs of 42% and 63% for the oral and ip delivery methods, respectively. In pharmacokinetic studies, (E/Z)-Zotiraciclib shows moderate to high systemic clearance (relative to liver blood flow), high volume of distribution (>0.6 L/kg), the oral bioavailability of 24%, ~4 and 37% in mice, rats, and dogs, respectively; and extensive tissue distribution in mice.
• In Vitro:
  (E/Z)-Zotiraciclib has a highly novel kinase inhibitory spectrum inhibiting 17 kinases from a panel of 63, 11 of which are CDK/JAK/FLT family members. Human CYP1A2, 3A4, 2C9, and 2C19 isoforms are not inhibited by (E/Z)-Zotiraciclib at the highest tested concentration of 25 μM, but (E/Z)-Zotiraciclib inhibits CYP2D6 with an IC50 of 0.95 μM, approximately at the plasma Cmax observed at the maximum tolerated dose. (E/Z)-Zotiraciclib inhibits cell proliferation concentrations in HCT-116 with an IC50 of 0.079 μM and HL-60 with an IC50 of 0.059 μM. (E/Z)-Zotiraciclib is a novel small molecule potent CDK/JAK2/FLT3 inhibitor and mainly metabolized by CYP3A4 and CY1A2 in vitro.

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

Inhibitor, leukemias, Fms like tyrosine kinase 3, FLT3, multiple myeloma, JAK, JAK2, Janus kinase, inhibit, Cluster of differentiation antigen 135, CD135, CDK2, CDK, Cyclin dependent kinase, (E/Z) Zotiraciclib, (E/Z)-SB 1317, (E/Z)-SB1317, (E/Z)-SB-1317, (E/Z)-TG02, (E/Z)Zotiraciclib, (E/Z)-Zotiraciclib, cancer

Compound Identifiers

PubChem CID

67354554