Isocryptotanshinone

Isocryptotanshinone is a dual STAT3 and PTP1B (IC₅₀ = 56.1 μM) inhibitor. Isocryptotanshinone inhibits STAT3 by binding to the STAT3 SH2 domain to block phosphorylation and nuclear translocation^[1][2]. Isocryptotanshinone exerts its anti-proliferative effect via the induction of cell cycle arrest, apoptosis, and pro-death autophagy, through the regulation of STAT3, AKT/mTOR and MAPK signaling pathways. Isocryptotanshinone suppresses the xenograft gastric cancer (GC) tumor growth in BALB/c nude mice. Isocryptotanshinone can be used for cancer research, such as lung cancer, breast cancer and GC^[1][3][4]. IC50 & Target:IC50: STAT3^[1], 56.1 μM (PTP1B)^[2]. In Vitro:Isocryptotanshinone (ICTS) (0-5 μM, 0-24 h) inhibits the constitutive STAT3 and p-STAT3 expression in A549 cells in a concentration- and time-dependent manner^[1].
Isocryptotanshinone (5 μM, 12 h) decreases STAT3 in the cytoplasm and p-STAT3 in nucleus in A549 cells^[1].
Isocryptotanshinone (5 μM, 0-4 h) inhibits the IL-6 (25 ng/mL)-stimulated expression of p-STAT3 in A549 cells in a time-dependent manner and almost completely abolishes p-STAT3 expression after 4 h^[1].
Isocryptotanshinone (0-10 μM, 0-24 h) attenuates the expression of survival-related proteins (Bcl-2, Bcl-xL, survivin, Mcl-1) in a time-dependent manner, and suppresses the expression of upstream regulators (EGFR and JAK2) in a concentration-dependent manner^[1].
Isocryptotanshinone (0-20 μM, 0-24 h) significantly inhibits the proliferation of A549 and 95D lung cancer cells in a concentration-dependent manner and induces apoptosis in A549 cells by remarkably increasing early apoptotic cell fractions, caspase 3/7 activity, and the expression of cleaved PARP^[1].
Isocryptotanshinone (0-10 μM, 0-24 h) induces pro-death autophagy in A549 cells by upregulating LC3II expression, promoting the accumulation of autophagic vacuoles and autolysosomes, and inhibiting the AKT/mTOR signaling pathway, similar to Cryptotanshinone (HY-N0174)^[1].
Isocryptotanshinone (0-20 μM, 24 h) inhibits proliferation (IC₅₀ = 12.5 μM) and colony formation in MCF-7 cells by inducing G1 phase cell cycle arrest and triggering early apoptosis^[3].
Isocryptotanshinone (2.5-10 μM, 0-24 h) triggers MAPK signaling activation in MCF-7 cells, which is characterized by the time- and concentration-dependent phosphorylation of JNK, ERK, and p38 MAPK^[3].
Isocryptotanshinone (0-40 μM, 0-72 h) suppressed the proliferation of GC cells, with IC₅₀ of 6.77 μM for SGC-7901 cells and 33.1 μM for MKN-45 cells^[4].
Isocryptotanshinone (0-40 μM, 24 h) induces G1/G0 phase cell cycle arrest and apoptosis in GC cells (SGC-7901 and MKN-45), an effect mediated through the inhibition of the STAT3 signaling pathway and the subsequent downregulation of cell cycle- and apoptosis-associated proteins (Cyclin D1, E2F1, Mcl-1, Bcl-2, survivin)^[4]. In Vivo:Isocryptotanshinone (20 mg/kg, i.p., every other day for 4 weeks) inhibits SGC-7901 xenograft tumor growth in BALB/c nude mice^[4].