Angiogénese

Compound 26F: potent enzyme inhibitor (IC50=28.2nM), low cytotoxicity (IC50=3.32μM), induces dose-dependent apoptosis in MDA-MB-231, blocks G0/G1 phase.

<p>DA-0157 is an orally active inhibitor targeting EGFR and ALK, designed to overcome resistance mutations in non-small cell lung cancer (NSCLC). It effectively inhibits the proliferation of Ba/F3-EGFR Del19/T790M/C797S (IC50= 6.9 nM), Ba/F3-EGFR WT (IC50= 0.83 μM), Ba/F3-EML4-ALK-L1196M (IC50= 5.5 nM), and Ba/F3-EML4-ALK (IC50= 7.4 nM). Additionally, DA-0157 inhibits CYP2D6 with an IC50 of 5.26 μM and demonstrates antitumor activity in mouse models.</p>

JAK2-IN-11 (Example 6) is a JAK2 kinase inhibitor with potent antitumor activity, exhibiting an IC50 of ≤10 nM against JH2 BIND WT/V617F. This compound effectively suppresses tumor growth.

<p>Milpecitinib (Compound 21a) is a potent and selective Janus tyrosine kinase (JAK) inhibitor with anti-inflammatory properties. It shows promise for research in cancer and inflammatory diseases.</p>

ALK/PI3K/AKT-IN-1 (Compound 45) effectively inhibits the proliferation of cancer cell lines A549, H1975, and PC9, with IC50 values of 0.44, 0.83, and 1.51 μM, respectively. This compound enhances the expression of p21 and p27, and decreases the activity of CDK2 and p-Rb, causing cell cycle arrest at the G1 phase. It suppresses the ALK/PI3K/AKT signaling pathway, promotes mitochondrial membrane potential depolarization, and induces apoptosis in A549 cells. Furthermore, ALK/PI3K/AKT-IN-1 inhibits the formation and growth of A549 cell spheres.

JAK-2-/3-IN-3 (ST4j) is a potent JAK2/3 inhibitor for leukemia research, with IC50s: JAK2, 13 nM; JAK3, 14.86 nM; induces apoptosis.

FAK-IN-2: potent oral FAK inhibitor, IC50 35 nM, reduces tumor growth, migration, and induces cell death.

HER2-IN-9, an oral HER2 inhibitor (IC50: 0.03 μM), hinders growth and spread of HER2+ breast cancer.

VEGFR-2-IN-65 (Compound 07) functions as a VEGFR-2 inhibitor. It forms hydrogen bonds with Cys180 and can inhibit tube formation in HUVECs.

EGFR/BRAF-IN-1 inhibits EGFR/BRAF (BRAFV600E IC50: 45 nM, GI50: 35 nM) and has antioxidant properties.

Multi-kinase inhibitor 4 (compound 14) serves as an orally effective inhibitor targeting FLT1, KDR, FLT3, FLT4, PDGFRα, and PDGFRβ, exhibiting IC50 values of 1.97 nM, 1.04 nM, 0.33 nM, 1.44 nM, 0.18 nM, and 0.89 nM respectively. This compound plays a crucial role in cancer research.

EGFR-IN-147 (compound ID-5841161) is a potent EGFR inhibitor, demonstrating a 14% inhibition rate at a concentration of 1μM. It holds promise for cancer research applications.

YSY01A is a proteasome inhibitor that suppresses cancer cell survival by inducing apoptosis (Apoptosis). It demonstrates IC50 values against various cell lines such as HEK293T, A549, MCF-7, MGC-803, and PC-3M with values of 51.01, 9.21, 5.21, 8.9, and 35.4 nM respectively. Additionally, YSY01A serves as a degrader of gp130 and JAK2, eliminating constitutive STAT3 signaling in human A549 lung cancer cells by downregulating gp130 and JAK2. YSY01A holds potential for research in cancer therapeutics.

Siphonaxanthin is a carotenoid found in green algae, known for targeting the death receptor 5 (DR5) on cancer cells to induce apoptosis. In human leukemia HL-60 cells, it increases DR5 expression, reduces Bcl-2 levels, and activates caspase-3. It also inhibits fibroblast growth factor receptor-1 (FGFR-1) signaling in endothelial cells. Siphonaxanthin suppresses the proliferation, migration, and tubular formation of human umbilical vein endothelial cells (HUVECs), as well as the growth of microvessels in rat aorta rings. Additionally, it has anti-inflammatory properties by blocking the translocation of high-affinity IgE receptors (FcεRI) to lipid rafts in mast cells. Siphonaxanthin shows potential for research into diseases such as cancer, diabetic retinopathy, and rheumatoid arthritis.

<p>LNK01004 is a JAK inhibitor that exhibits potent inhibitory effects on JAK1 (IC50: 10 nM), JAK2 (IC50: ＜0.51 nM), and TYK2 (IC50: 1.0 nM). It can concurrently inhibit multiple cytokine-induced p-STAT signaling pathways and is applicable for research on diseases such as atopic dermatitis.</p>

<p>CDD-1115 is a potent and selective BMPR2 inhibitor, with an IC50 of 1.8 nM and a Kiapp of 6.2 nM. It effectively suppresses gene expression mediated by bone morphogenetic proteins (BMPs). BMPs regulate cellular processes in various tissue types, such as the kidneys, skeletal muscle, heart, and reproductive organs, and can induce ectopic bone formation.</p>

2,5-Di-tert-butyl-1,4-benzoquinone is a potent antibacterial agent found primarily in marine Streptomyces sp. VITVSK1, effective against emerging antibiotic resistance. Additionally, it serves as a powerful inhibitor of RNA polymerase.

EGFR-IN-126 (compound 9d) is an effective inhibitor of EGFR L858R/T790M/C797S, displaying an IC50 value of 0.005 μM. It exhibits antitumor activity both in vivo and in vitro.

SILA-123, an inhibitor of FLT3 (FLT3-WT: IC50=2.1 nM; FLT3-ITD: IC50=1.0 nM), induces cell apoptosis by hindering the cell cycle progression at the G0/G1 phase through the suppression of FLT3 phosphorylation and its downstream signaling pathways. This compound is utilized in the study of acute myeloid leukemia.

<p>Lirucitinib is a JAK inhibitor known for its anti-inflammatory properties.</p>