KA2507

• CAT Number: I044472
• CAS Number: 1636894-46-6
• Molecular Formula: C16H14N6O2
• Molecular Weight: 322.32
• Purity: ≥95%
• Synonyms: 4-[[di(pyrazin-2-yl)amino]methyl]-N-hydroxybenzamide
• InChI: InChI=1S/C16H14N6O2/c23-16(21-24)13-3-1-12(2-4-13)11-22(14-9-17-5-7-19-14)15-10-18-6-8-20-15/h1-10,24H,11H2,(H,21,23)
• InChIKey: LXHMTDHBMRZSHJ-UHFFFAOYSA-N
• SMILES: C1=CC(=CC=C1CN(C2=NC=CN=C2)C3=NC=CN=C3)C(=O)NO

KA2507 is a potent, orally active and selective HDAC6 inhibitor, with an IC50 of 2.5 nM. KA2507 shows antitumor activities and immune modulatory effects in preclinical models[1].
KA2507 did not inhibit the in vitro proliferation of mouse or human cancer cells at concentrations that are selective for HDAC6 inhibition[1].
KA2507 (100-200 mg/kg; p.o.; daily; for 20 days) inhibits tumor growth in the syngeneic B16-F10 mouse melanoma model[1].
KA2507 also demonstrates antitumor efficacy in CT26 and MC38 colorectal cancer models[1].
Analysis of tumor samples also indicates modulation of biomarkers of antitumor immunity at efficacious dosing, with KA2507 administration resulting in reduced STAT3 activation (as measured by phospho-STAT3, an important suppressor of the antitumor immune response), reduced PD-L1 expression, and increased expression of MHC class I[1].
KA2507 exhibits poor oral bioavailability (mice 15%) and Cmax (mice 300 ng/mL) following oral administration (mice 200 mg/kg)[1].

Reference

[1]. Apostolia M Tsimberidou, et al. Preclinical Development and First-in-Human Study of KA2507, a Selective and Potent Inhibitor of Histone Deacetylase 6, for Patients with Refractory Solid Tumors. Clin Cancer Res. 2021 May 4.
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