pi3kα-in-4

PI3Kα-IN-4 is a potent, selective, and orally active PI3Kα inhibitor with an IC50 of 1.8 nM, demonstrating antitumor activity [1].

(S)-PI3Kα-IN-4, a potent inhibitor of PI3Kα with an IC50 of 2.3 nM, demonstrates 38.3-, 4.25-, and 4.93-fold selectivity over PI3Kβ, PI3Kδ, and PI3Kγ, respectively, and is suitable for cancer research[1]. (S)-PI3Kα-IN-4 (compound 11) is a quinazolin-4(3H)-one derivative with 2-substituted-N-methylpropanamide substitution[1].

PI3K-IN-46 is a specific inhibitor of PI3Kγ.

PI3K-IN-47 (Compound 27) is a potent bivalent inhibitor targeting the phosphoinositide 3-kinases (PI3K) family, with IC50 values of 0.44 nM for PI3Kα, and 7.18 nM, 13.92 nM, and 22.83 nM for PI3Kβ, PI3Kγ, and PI3Kδ respectively. It induces G1 phase cell cycle arrest and exhibits anti-neoplastic properties by restraining colony formation and cell migration. Additionally, PI3K-IN-47 has demonstrated the ability to suppress tumor growth in HGC-27 xenograft mouse models [1].

PI3K-IN-41 (compound 2), a photocaged PI3K inhibitor (IC50=18.92 nM) with anticancer properties, demonstrates potent PI3K inhibition following UV light irradiation and has been shown to enhance antitumor effects [1]. This compound has potential for use in precisely controlled cancer therapeutics.

PI3K-IN-48, a PI3K inhibitor, exhibits an IC50 of 1.55 ± 0.18 μM in A549 cells, demonstrating its potency in this context. It induces G0/G1 phase arrest and cell apoptosis, while also down-regulating the expression of p-PI3K and p-Akt. This compound is relevant for research into the treatment of human lung cancers [1].

PI3K-IN-49 is a powerful inhibitor of PI3K, demonstrating antiproliferative effects on Avg T-47D and Avg SKBR3 cells (WO2023239710A1; example 29) [1].

PI4KIIIbeta-IN-10 is a potent inhibitor of PI4KIIIβ with an IC50 value of 3.6 nM.

PI4KIIIbeta-IN-9 is a potent inhibitor of PI4KIIIβ [IC50 of 7 nM].

AMG 511 is a potent and orally available pan inhibitor of class I PI3Ks (Kis of 4 nM, 6 nM, 2 nM, and 1 nM for PI3Kα, β, δ, and γ, respectively), exhibiting anti-tumor activity in a mouse glioblastoma xenograft model[1]. AMG 511 significantly suppresses PI3K signaling as indicated by a decrease in p-Akt (Ser473).

PI3K/HDAC-IN-4 (Compound 31f) is a dual inhibitor targeting PI3K and HDAC, with an IC50 of 0.2μM. It demonstrates high selectivity for HDAC1-3, with IC50 values of 75.5 nM, 70.9 nM, and 1.9 nM, respectively. As a potent pan-PI3K inhibitor, PI3K/HDAC-IN-4 has IC50 values of 2.5 nM, 80.5 nM, 10.0 nM, and 57.2 nM for PI3Kα, β, δ, and γ, respectively. This compound effectively induces apoptosis in tumor cells by concurrently inhibiting the PI3K/AKT/mTOR signaling pathway and HDAC1-3. It shows significant antiproliferative activity across various tumor cell lines, such as MV4-11, Jeko-1, HL60, and MCF-7, with IC50 values of 0.2, 0.9, 0.8, and 1.5 μM, respectively. PI3K/HDAC-IN-4 is applicable in the study of lymphoma and leukemia.

Bimiralisib (PI3K-IN-2) is an orally bioavailable pan inhibitor of PI3K and inhibitor of the mTOR, with potential antineoplastic activity. PI3K-IN-2 inhibits the PI3K kinase isoforms alpha, beta, gamma and delta and, to a lesser extent, mTOR kinase, which may result in tumor cell apoptosis and growth inhibition in cells overexpressing PI3K/mTOR. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to both chemotherapy and radiotherapy.

Onatasertib (CC223) is an orally available mTOR inhibitor with potential antitumor activity. Onatasertib inhibits the activity of mTOR, which may result in the induction of tumor cell apoptosis and a decrease in tumor cell proliferation. Onatasertib is a potent mTOR kinase inhibitor (IC50: 16 nM), with >150-fold sensitivity than the related lipid kinase PI3Kα (IC50: 4 μM).

PI3Kα-IN-17 (example 4), a potent PI3K α inhibitor [1], effectively targets the enzyme.