PI3Kβ Inhibitor

PI3K-IN-33 (Compound 6e) is a highly selective PI3K inhibitor with IC₅₀ values of 11.73, 6.09 and 11.18 μM for PI3K-α、PI3K-β and PI3K-δ , respectively. PI3K-IN-33 arrests cell cycle at G2/M phase and induces apoptosis. PI3K-IN-33 can be used in leukemia research.

DHW-221 is a potent orally active dual PI3K/mTOR inhibitor, exhibiting low nanomolar potency against all four Class I PI3K isoforms and mTOR (PI3Kα, IC₅₀ = 0.50 nM; PI3Kβ, IC₅₀ = 1.9 nM; PI3Kγ, IC₅₀ = 1.8 nM; PI3Kδ, IC₅₀ = 0.74 nM; mTOR, IC₅₀ = 3.9 nM). DHW-221 exerts antitumor effects by blocking the PI3K/Akt/mTOR pathway and inducing mitochondrial apoptosis and paraptosis (via Endoplasmic Reticulum (ER) stress and MAPK signaling) and arrests cell cycle, thereby inhibiting cell migration, invasion and angiogenesis. DHW-221 inhibits tumor growth in both the A549/Taxol (HY-B0015) and the HCC827 xenograft mouse models. DHW-221 can be used for non-small cell lung cancer (NSCLC), colon and breast cancer research.

NVP-CLR457 (compound 40) is an orally active, potent and balanced pan-class I PI3K inhibitor. NVP-CLR457 shows a clear dose-dependent PK/PD/efficacy relationship. NVP-CLR457 has antitumor activity.

TGX-155 (AZ12649385) is a selective inhibitor of PI3Kβ. TGX-155 has potential applications in antithrombotic therapy.

PI3K-IN-34 (Compound 6g) is a highly selective PI3K inhibitor with IC₅₀ values of 11.73, 6.09 and 11.18 μM for PI3K-α、PI3K-β and PI3K-δ , respectively. PI3K-IN-34 arrests cell cycle at G2/M phase and induces apoptosis. PI3K-IN-34 can be used in leukemia research.

PI3K/HDAC-IN-2 is a potent dual PI3K/HDAC inhibitor with IC₅₀s of 226 nM, 279 nM, 467 nM, 29 nM for PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ, respectively, and IC₅₀s of 1.3 nM, 3.4 nM, 972 nM, 17 nM, 12 nM for HDAC1, HDAC2, HDC4, HDAC6, HDAC8, respectively. PI3K/HDAC-IN-2 exhibits PI3Kδ and class I and IIb HDAC selectivity. PI3K/HDAC-IN-2 has remarkable anticancer effects.

Pabgraminone C (IM502) is a Fungal metabolite and PI3Kγ inhibitor with an IC₅₀ of 61.7 nM against PI3Kγ. Pabgraminone C shifts the STAT signaling pathway in cells from an immunosuppressive STAT3/STAT6-dominant profile to an immunostimulatory STAT1/STAT2-dominant profile, driving cells toward a pro-inflammatory phenotype. Pabgraminone C reprograms cells from an immunosuppressive state to an immunostimulatory state, reversing their suppressive effect on anti-tumor immunity. Pabgraminone C inhibits established tumor growth and metastasis across multiple cancer types. Pabgraminone C overcomes resistance to PD-1 checkpoint blockade strategies. Pabgraminone C can be used in research related to liver cancer, melanoma, and colorectal cancer.

PI3Kα-IN-29 is a potent, orally active and selective PI3Kα with an IC₅₀ of 2.5 nM. PI3Kα-IN-29 exhibits >400-fold selectivity over PI3Kβ/δ/γ/mTOR. PI3Kα-IN-29 selectively degrades the H1047R mutant p110α protein and inhibits PI3Kα kinase activity. PI3Kα-IN-29 suppresses PI3K/AKT/mTOR signaling, induces G1 arrest, and inhibits migration. PI3Kα-IN-29 inhibits tumor growth in a T47 mouse model. PI3Kα-IN-29 can be used for the research of breast cancer.

PI3K/HDAC-IN-5 is a dual PI3K/HDAC inhibitor. PI3K/HDAC-IN-5 inhibits PI3Kα, PI3Kβ, PI3Kγ, and PI3Kδ (IC₅₀ values of 25.41, 134.52, 166.75, and 41.58 nM, respectively) and inhibits downstream PI3K/AKT signaling. PI3K/HDAC-IN-5 inhibits HDAC6, HDAC8, and HDAC11 (IC₅₀ values of 29.35, 157.27, and 382.26 nM, respectively), increases α-tubulin and SMC3 acetylation, while not affecting histone H3/H4 acetylation. PI3K/HDAC-IN-5 induces S phase cell cycle arrest and apoptosis, and inhibits the proliferation of cervical cancer cell lines. PI3K/HDAC-IN-5 can be used for research on cervical cancer.

PI3K/mTOR-IN-20 is a selective dual PI3K/mTOR inhibitor. PI3K/mTOR-IN-20 demonstrates nanomolar antiproliferative effects with IC₅₀s of 0.380 and 0.090 μM for MRC-5 and Mlg2908 cells. PI3K/mTOR-IN-20 reduces Ashcroft scores, hydroxyproline content, collagen deposition, and downregulates fibrosis-related proteins, while restoring lung architecture in a Bleomycin-induced pulmonary fibrosis model. PI3K/mTOR-IN-20 shows a favorable safety profile with steady weight recovery and no distinct liver or kidney toxicity. PI3K/mTOR-IN-20 can be used for fetal lung fibroblasts research.

PI3Kδ-IN-22 (Compound 26) is a selective inhibitor for PI3Kδ with pK_i of 9.3. PI3Kδ-IN-22 inhibits PI3Kδ-AKT signaling pathway in THP-1 cells, with pIC₅₀ of 9.4. PI3Kδ-IN-22 exhibits good pharmacokinetic characters in rats.

Rac)-AZD8186 is the racemate of AZD8186 (HY-12330), a PI3K inhibitor that inhibits PI3Kβ (IC₅₀=4 nM), PI3Kδ (IC₅₀=12 nM), PI3Kα (IC₅₀=35 nM) and PI3Kγ (IC₅₀=675 nM).

MEK/PI3K-IN-2 (compound 6s) is a potent MEK/PI3K inhibitor, with IC₅₀ values of 352 nM (MEK1), 107 nM (PI3Kα), and 137 nM (PI3Kδ), respectively. MEK/PI3K-IN-2 suppresses pAKT and pERK1/2 levels. MEK/PI3K-IN-2 shows anti-proliferative activity against tumor cell lines.

PP487 is a selective dual inhibitor of Tyrosine kinase/PI3-K, with IC₅₀ values of 0.017 μM, 0.072 μM, 0.004 μM, 0.01 μM, 0.55 μM, 0.22 μM, and < 0.01 μM against DNA-PK, mTOR, Hck, Src, EGFR, EphB4, and PDGFR, respectively. PP487 can be used in cancer research.

LCI40 is an orally active dual PI3K/BRD4 inhibitor (PI3Kα IC₅₀ = 0.071 μM, PI3Kβ IC_{50 =} 0.17 μM, PI3Kγ IC₅₀ = 0.66 μM, PI3Kδ IC₅₀ = 0.072 μM, BRD4 BD1 IC₅₀ = 0.19 μM, and BRD4 BD2 IC₅₀ = 1.88 μM. LCI40 inhibits phosphorylation of pAKT (S473) and suppresses c-MYC levels in mantle cell lymphoma cells. LCI40 displays immunomodulatory capacity with minimal toxicity to normal mouse immune cells. LCI40 can be used for the research of mantle cell lymphoma.

PI3Kα-IN-7 (Compound A12) is a potent PI3Kα inhibitor. PI3Kα-IN-7 also inhibits PI3Kβ. PI3Kα-IN-7 decreases cancer cells mitochondrial membrane potential and induces apoptosis.

PI3K-IN-35 (Compound 6l) is a highly selective PI3K inhibitor with IC₅₀ values of 13.98, 7.22 and 10.94 μM for PI3K-α、PI3K-β and PI3K-δ, respectively. PI3K-IN-35 arrests cell cycle at G2/M phase and induces apoptosis. PI3K-IN-35 can be used in leukemia research.

HM5023507 is an orally active and selective PI3Kδ/γ inhibitor with IC₅₀s of 4  and 5  μM for PI3Kδ and PI3Kγ over PI3Kβ and PI3Kα. HM5023507 attenuates the PI3Kδ/γ signaling in human basophils. HM5023507 also attenuates the activation and function of human B and T cells and cytokine and IgG production during cocultures, and Th17 differentiation of CD4 T cells. HM5023507 inhibited semiestablished collagen-induced arthritic inflammation in the rat models. HM5023507 can be used for inflammatory diseases like rheumatoid arthritis research.

PI3Kγ inhibitor 7 (compound 2) is a potent and orally active PI3Kγ inhibitor with IC₅₀ values of 4768, 878.1, 3.42, 355.2 nM for PI3Kα, PI3Kβ, PI3Kγ, PI3Kδ, respectively. PI3Kγ inhibitor 7 shows antitumor activity. PI3Kγ inhibitor 7 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

MEK/PI3K-IN-1 (compound 6r) is a potent MEK/PI3K inhibitor, with IC₅₀ values of 124 nM (MEK1), 130 nM (PI3Kα), and 236 nM (PI3Kδ), respectively. MEK/PI3K-IN-1 suppresses pAKT and pERK1/2 levels. MEK/PI3K-IN-1 shows anti-proliferative activity against tumor cell lines.