MELK-8a hydrochloride

SKU: orb1309437

Description

MELK-8a hydrochloride is a highly potent small molecule inhibitor of Maternal Embryine Leucine Zipper Kinase (MELK), exhibiting an IC50 of 2 nM. This compound is a valuable research tool for investigating MELK function in cancer biology, stem cell regulation, and tumorigenesis in both cellular and animal models.

Research Area

Cell Biology, Signal Transduction

Key Properties

• CAS Number: 2096992-20-8
• MW: 469.02
• Purity: 99.57% (May vary between batches)
• Formula: C₂₅H₃₃ClN₆O
• SMILES: Cl.CN1CCN(CC1)c1ccc(cc1)-n1cc(cn1)-c1ccncc1OCC1CCNCC1
• Target: MELK
• Solubility: H2O:100 mg/mL (213.21 mM);DMSO:8 mg/mL (17.06 mM)

Bioactivity

• Target IC50:
  MELK:2 nM
• In Vivo:
  In C57BL/6 mice, MELK-8a hydrochloride (30 mg/kg; s.c.) results in good plasma exposure. The compound adsorption into the systemic circulation is rapid (Tmax=0.4 h) and peak plasma concentration reaches 6.6 μM. An ascending dose PK study in female athymic nude mice shows that the rate of compound release is maximal at 120 mg/kg and all clearance mechanisms can be saturated at 240 mg/kg. However, MELK-8a hydrochloride (10 mg/kg; oral) shows very poor PK (3.6% oral bioavailability) consistent with very high in vivo clearance.
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• In Vitro:
  MELK-8a hydrochloride inhibits the growth of MDA-MB-468 cells and MCF-7 cells with an IC50 of approximately 0.06 and 1.2 μM, respectively. MELK-8a hydrochloride remains very potent with an IC50 of 140 nM when the ATP concentration in the biochemical assay is shifted from 20 μM to 2 mM. MELK-8a hydrochloride only inhibits seven off-target kinases in addition to MELK with >85% inhibition of binding at 1 μM demonstrating great selectivity. MELK-8a hydrochloride is at least 90-fold more selective in targeting MELK in all cases. MELK-8a hydrochloride is fairly soluble (0.22 g/L at pH 6.8) and shows a good permeability in the Caco-2 assay.
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

inhibit, NVS-MELK8a, Maternal embryonic leucine zipper kinase, MELK, MELK 8a hydrochloride, MELK-8a, MELK8a hydrochloride, MELK-8a Hydrochloride, Inhibitor

Compound Identifiers

PubChem CID

126843227