CW069

• CAT Number: I002020
• CAS Number: 1594094-64-0
• Molecular Formula: C₂₃H₂₁IN₂O₃
• Molecular Weight: 500.33
• Purity: ≥95%
• Synonyms: 2-[[(2S)-2-(benzylamino)-3-phenylpropanoyl]amino]-5-iodobenzoic acid
• Target: Microtubule/Tubulin
• Solubility: DMSO: ≥ 52 mg/mL
• Storage: Store at -20 C
• IC50: 75 ± 20 μM [1]
• InChI: InChI=1S/C23H21IN2O3/c24-18-11-12-20(19(14-18)23(28)29)26-22(27)21(13-16-7-3-1-4-8-16)25-15-17-9-5-2-6-10-17/h1-12,14,21,25H,13,15H2,(H,26,27)(H,28,29)/t21-/m0/s1
• InChIKey: IRDIXDXDSUBHIU-NRFANRHFSA-N
• SMILES: C1=CC=C(C=C1)C[[email protected]@H](C(=O)NC2=C(C=C(C=C2)I)C(=O)O)NCC3=CC=CC=C3

CW069（Cat No.:I002020） is a selective allosteric inhibitor of HSET, a microtubule motor protein. It exhibits an IC50 of 75 μM, indicating its potency in inhibiting HSET activity. Notably, CW069 demonstrates a significantly higher selectivity for HSET compared to KSP, another microtubule motor protein. This high selectivity suggests that CW069 specifically targets HSET without interfering with the function of KSP. Such selectivity makes CW069 a promising candidate for studying and modulating HSET-related cellular processes and potential therapeutic interventions.

Reference

[1]. Watts CA, et al. Design, synthesis, and biological evaluation of an allosteric inhibitor of HSET that targets cancer cells with supernumerary centrosomes. Chem Biol. 2013 Nov 21;20(11):1399-410.
Abstract
Centrosomes associate with spindle poles; thus, the presence of two centrosomes promotes bipolar spindle assembly in normal cells. Cancer cells often contain supernumerary centrosomes, and to avoid multipolar mitosis and cell death, these are clustered into two poles by the microtubule motor protein HSET. We report the discovery of an allosteric inhibitor of HSET, CW069, which we designed using a methodology on an interface of chemistry and biology. Using this approach, we explored millions of compounds in silico and utilized convergent syntheses. Only compound CW069 showed marked activity against HSET in vitro. The inhibitor induced multipolar mitoses only in cells containing supernumerary centrosomes. CW069 therefore constitutes a valuable tool for probing HSET function and, by reducing the growth of cells containing supernumerary centrosomes, paves the way for new cancer therapeutics.