Bimiralisib (hydrochloride)

Bimiralisib hydrochloride (PQR309 hydrochloride) is an orally active, blood-brain barrier-penetrant PI3K/mTOR inhibitor with in vitro antiproliferative activity and in vivo antitumor activity. Bimiralisib hydrochloride induces G1 cell cycle arrest, apoptosis and cell death in cancer cells, while inhibiting cancer cell proliferation, migration, invasion, colony formation and spheroid generation. Bimiralisib hydrochloride upregulates the expression of E2F4. The combination of Bimiralisib hydrochloride with venetoclax enhances therapeutic efficacy in acute myeloid leukemia models. Bimiralisib hydrochloride can be used in cancer-related research^[1][2][3][4]. IC50 & Target:IC50: 33 nM (PI3Kα), 451 nM (PI3Kδ), 661 nM (PI3Kβ), 708 nM (PI3Kγ), 36 nM (PI3Kα-H1047R), 63 nM (PI3Kα-E542K), 136 nM (PI3Kα-E545K), 89 nM (mTOR), 8486 nM (VPS34), 8567 nM (DNAPK)^[1] Kd: 1.5 nM (PI3Kα), 11 nM (PI3Kβ), 25 nM (PI3Kδ), 25 nM (PI3Kγ), 12 nM (mTOR), 230 nM (VPS34), 850 nM (PI3KC2β), 40000 nM (PI4KCβ), 1600 nM (DNAPK)^[1] mTORC1, mTORC2^[2] In Vitro:Bimiralisib hydrochloride inhibits the proliferation and induces apoptosis of human glioblastoma U87 and U251 cells, reduces the migration and invasion abilities of glioma cells, and also induces G1-phase cell cycle arrest in a dose-dependent manner^[1].
Bimiralisib (PQR-309) hydrochloride reduces the viability of OCI-Ly1 diffuse large B-cell lymphoma (DLBCL) cells, MOLM-13 acute myeloid leukemia (AML) cells, mL-2 and SKM-1 AML cells, HL-60 AML cells, as well as OCI-AML3, PL-21 and MOLM-16 AML cells, with corresponding IC₅₀ values of 1 μM, 2 μM, 3 μM, 5 μM and 10 μM^[2].
Bimiralisib (1 μM alone or combined with 100 nM Venetoclax (HY-15531); 20 h) hydrochloride exhibits reduced cytotoxic potency in MOLM-13, SKM-1 and OCI-AML3 acute myeloid leukemia (AML) cells due to the protective effect of bone marrow stroma^[2].
Bimiralisib (0.312-20.0 μM; 72 h) hydrochloride potently inhibits the viability of human gastric cancer cell lines SNU-484, SNU-668 and AGS, with IC₅₀ values of 0.792 μM, 0.419 μM and 0.611 μM, respectively^[3].
Bimiralisib (0.312-1.25 μM; 8 days) hydrochloride inhibits clonogenic growth of SNU-484, SNU-668 and AGS human gastric cancer cells^[3].
Bimiralisib (0.312-1.25 μM; 14 days) hydrochloride inhibits the anchorage-independent sphere growth of SNU-484, SNU-668 and AGS human gastric cancer cells^[3].
Bimiralisib (0.625-1.25 μM; 24 h) hydrochloride effectively inhibits the PI3K/mTOR signaling pathway in SNU-484 and AGS human gastric cancer cells by reducing the phosphorylation levels of AKT, mTOR and p70S6K. It also induces G1-phase cell cycle arrest in SNU-484 and AGS human gastric cancer cells and regulates the expression of G1-phase cell cycle regulatory proteins, specifically characterized by upregulated expression of E2F4, p107 and (in AGS cells) p21, and downregulated expression of Cyclin E^[3].
Bimiralisib (0.625-1.25 μM; 48 h) hydrochloride inhibits the migratory capacity of human gastric cancer cells SNU-484 and AGS under low-serum (1% FBS) conditions; it regulates the expression of epithelial-mesenchymal transition-related markers in human gastric cancer cells SNU-484 and AGS, upregulating E-cadherin expression and downregulating vimentin expression^[3].
Bimiralisib hydrochloride has IC₅₀ values ​​of 36 nM, 63 nM and 136 nM for PI3Kα-H1047R, PI3Kα-E542K and PI3Kα-E545K, respectively^[4]. In Vivo:Bimiralisib (p.o.) hydrochloride demonstrates in vivo antitumor activity and does not induce hepatotoxicity in female rats 24 hours after oral administration^[1].