ac1in1

AC1-IN-1 is a selective inhibitor of adenylyl cyclase type 1 (AC1, IC50 = 0.54 µM).

IMPDHII/HDAC1-IN-1 (Compound C12) is an orally active dual inhibitor targeting IMPDHII and HDAC1, with IC50 values of 84.69 nM and 81.75 nM, respectively. It exhibits significant antitumor activity by inhibiting proliferation of K-562 cells (IC50 = 305.31 nM). By simultaneously targeting IMPDHII and HDAC1, this compound demonstrates a synergistic antitumor effect, suppressing tumor cell proliferation and inducing apoptosis. IMPDHII/HDAC1-IN-1 can be utilized in the study of cancers such as chronic myeloid leukemia (CML).

HDAC1-IN-11 (Compound 6) is an HDAC1 inhibitor with an IC50 of 106.6 nM. It suppresses the expression of Sp1 and RAD51, leading to Caspase-dependent apoptosis. HDAC1-IN-11 exhibits antitumor activity and enhances the sensitivity of Etoposide and Gemcitabine by promoting synergistic cell death in NSCLC through inhibiting homologous recombination and non-homologous end joining (NHEJ) pathways involved in DNA double-strand break repair. It is applicable in chemotherapy research for cancers such as NSCLC.

HDAC1-IN-12 is an inhibitor of the malignant malaria parasite (Plasmodium falciparum) HDAC1 (PfHDAC1), with an IC50 of 4.1 nM. This inhibitor functions by inhibiting PfHDAC1, increasing histone H3 acetylation in the P. falciparum parasite, and reducing the expression of genes associated with malaria invasion. It exhibits favorable safety profiles, improved physicochemical properties, and effective in vivo antimalarial activity, making HDAC1-IN-12 a valuable tool for malaria research.

HDAC1-IN-10 (Compound 2b) is a potent, selective, and orally active inhibitor of HDAC1 and HDAC2, with IC50 values of 6 nM and 190 nM, respectively. It exhibits IC50 values greater than 50 μM against HDAC3-8. This compound effectively inhibits the proliferation of HCT-116 cells with a GI50 of 155 nM and suppresses tumor growth in HCT-116 colon cancer xenograft models in nude mice. HDAC1-IN-10 is applicable for colon cancer research.

VEGFR2/HDAC1-IN-1 (compound 13) is a potent dual inhibitor of VEGFR-2 and HDAC, with IC50 values of 57.83 nM for VEGFR-2 and 9.82 nM for HDAC. It arrests the cell cycle at the S and G2 phases and induces apoptosis in HeLa cells, demonstrating an anti-angiogenic effect [1].