The novel synthetic flavone inhibitors (4'-hydroxyflavones) were identified with receptor-based virtual screening of combinatorial library containing 150,000 organic compounds. Followed in vitro tests revealed that 19 flavones out of 49 selected display ability to inhibit activity of CK2 (IC50 < 30 μM). After several cycles of their chemical optimization 31 new inhibitors with activity 0.004-8 μM have been obtained. The most active compound FNH79 has IC50 nearly 100 times lower than IC50 of fisetin, the most active natural flavone known to inhibit CK2. Initial selectivity tests of this compound using four serine/threonine (ASK1, JNK3, Aurora A, ROCK1) and three tyrosine protein kinases (FGFR1, Met, Tie2) as targets have revealed negligible its inhibitory activity.