Angiogénesis

<p>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>

DHFR-IN-4 is a potent dihydrofolate reductase (DHFR) inhibitor with anti-tumour activity, inhibits EGFR and HER2 and can be used to study pancreatic cancer.

<p>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.</p>

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.

LT-850-166 is a potent inhibitor of FLT3 and has shown efficacy in overcoming a wide range of FLT3 mutations.

<p>DualCathepsinL/JAK-IN-1 (Compound A8) serves as a dual inhibitor of Cathepsin L (CTSL) and JAK, exhibiting IC50 values of 0.68 μM for CTSL and 337.1 nM, 5.251 nM, 27.29 nM, and 172.6 nM for JAK1/2/3 and TYK2, respectively. This compound effectively prevents the activation of MAPK, NF-κB, and JAK/STAT signaling pathways, leading to significant anti-inflammatory therapeutic effects. DualCathepsinL/JAK-IN-1 is applicable in research on acute lung injury (ALI).</p>

<p>Protein kinase inhibitor 10 is a protein kinase inhibitor with IC50 values of 28.9 μM, 13.6 μM, and 2.41 μM for TAM receptors, FAK, and KIT, respectively. It can inhibit abnormal and excessive cell proliferation, showing potential for research in the field of cancer treatment.</p>

<p>HER2-IN-21 (compound 657994) is an inhibitor of the human epidermal growth factor receptor 2 (HER2) with an IC50 value of 3.85 μM.</p>

FAK-IN-21 (compound 9) is a FAK inhibitor with an IC50 value of 37.52 nM. It inhibits cell growth and the phosphorylation of FAK, making it useful for research into diffuse gastric cancer.

VEGFR/PDGFR-IN-1 (Compound 1) is an inhibitor of VEGFR with an IC50 of 0.4 μM. It can inhibit angiogenesis in HUVEC cells and holds promise for impeding tumor growth and metastasis.

HDHD4-IN-1 (compound 3) is an inhibitor of N-acetylneuraminate-9-phosphate phosphatase (HDHD4) with an IC50 value of 11 μM. It is utilized in the research of neurological disorders.

<p>TZEP7 functions as an EGFR kinase inhibitor in cancer cells. It exhibits cytotoxicity and induces apoptosis within these cells. TZEP7 downregulates the anti-apoptotic protein Bcl-2, upregulates the pro-apoptotic protein Bax, and increases caspase levels. This compound holds potential for research in anticancer drug development.</p>

(Rac)-PT2399 is a potent and specific inhibitor of hypoxia-inducible factor 2a (HIF-2α)(IC50 of 0.01 μM).

AFP464 (NSC710464) free base is an active HIF-1α inhibitor (IC50: 0.25 μM) and a potent aryl hydrocarbon receptor (AhR) activator.

<p>FGFR1inhibitor-17 (Compound 92) is a potent inhibitor of FGFR1, with promising applications in cancer research.</p>

TrxR/EGFR-IN-1 (Compound L1Au2) is a TrxR/EGFR inhibitor with activity against both gefitinib-sensitive and -resistant lung cancer, effectively suppressing tumor proliferation and promoting apoptosis. It enhances GPX4 degradation through autophagosome-lysosome and proteasome pathways, leading to ferroptosis. Additionally, it induces endoplasmic reticulum stress and triggers immunogenic cell death, making it applicable for studies on gefitinib-resistant lung cancer.

<p>Tyrosine kinase-IN-9 (Compound B) is an inhibitor of c-Abl. It is useful for studying neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease.</p>

<p>TGF-βRI inhibitor 3 (Compound 9ac) is a selective inhibitor of TGF-β that effectively suppresses the TGF-β signaling pathway. It exhibits IC50 values of 13 μM for c-Src kinase and 0.63 μM for ALK5 kinase.</p>

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

<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>JAK2 JH2 binder-1: potent, selective, Ki=37.1 nM, potential for studying myeloproliferative neoplasms.</p>

<p>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.</p>

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.

<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>

<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>

<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>

TTT 3002: oral FLT3 inhibitor for AML research, blocks D835 mutations, potent at 0.2 nM IC50.

BTK-IN-34 (compound 9h) functions as a selective BTK inhibitor, exhibiting antiproliferative effects in RAMOS cells by specifically targeting pBTK (Tyr223) while sparing upstream proteins such as Lyn and Syk in the BCR signaling pathway [1].

<p>EGFR-IN-48: potent EGFR inhibitor, oral, IC50: 0.193-66.7 nM, blocks EGFR mutants &amp; BaF3/PC-9 cell proliferation.</p>

Tarloxotinib bromide (TH-4000) is an irreversible inhibitor of EGFR/HER2.

FAK inhibitor7, a potent FAK inhibitor, demonstrates an IC50 of 3.58 nM. This compound effectively inhibits downstream signaling cascades of FAK (such as Src and AKT), which leads to cell cycle arrest at the G0/G1 phase and induces cytotoxic autophagy in ovarian cancer cells. Additionally, FAK inhibitor7 has been shown to suppress tumor metastasis and growth in ovarian cancer mouse models.

<p>MK-8457 is a dual inhibitor of SYK and ZAP70, valuable for rheumatoid arthritis research [1].</p>

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

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.

JAK1/TYK2-IN-3, orally active, selectively inhibits TYK2 (IC50: 6 nM), JAK1 (37 nM), JAK2 (140 nM), JAK3 (362 nM), and has anti-inflammatory effects.

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.

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.

Antiallergic agent-1, an Src family kinase inhibitor, is a new and valuable lead compound with potential as an anti-allergic agent.

E7090 succinate inhibits FGFR1, FGFR2, and FGFR3 with IC50: 0.71, 0.50, 1.2 nM; less so FGFR4 at 120 nM.

<p>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>

Tyrphostin 63 (compound 13) is an epidermal growth factor receptor (EGFR) inhibitor, with an IC50 of 375 μM and a Ki of 123 μM.

JAK1-IN-9 (compound 23a) is a potent, selective inhibitor of JAK1, demonstrating an IC50 of 72 nM.

Si306, an Src inhibitor, exhibits antitumor activity by reducing the phosphorylation of focal adhesion kinase (FAK) and the expression of epidermal growth factor receptor (EGFR), thereby inhibiting the invasion of human glioblastoma (GBM).

<p>FGFR1inhibitor-16 (Compound 89) functions as an FGFR1 inhibitor, demonstrating an inhibition rate of 53.00% at a concentration of 50 μM and 24.95% at 10 μM. It is utilized in tumor research.</p>

<p>FAK-IN-3 inhibits FAK, reduces PA-1 cell migration/invasion, and tumor growth, with no major side effects.</p>

<p>Protein Kinase Inhibitor 12 (compound 1-91) is protein kinase inhibitor,PIM-1, CDK-2, GSK-3, and SRC mammalian protein kinases.</p>

BTK-IN-6, a potent BTK inhibitor, may treat immune, cardiac, cancer, viral, inflammatory, metabolic, and neurological disorders.

(S)-3-Hydroxy Midostaurin is a potent inhibitor of kinases(IC50 of <400 nM for 13 kinases (VEGFR-2, TRK-A, FLT3, et)).

JAK2/FLT3-IN-1 (TFA), an oral JAK2/FLT3 inhibitor, shows anticancer properties; IC50: JAK2 (0.7 nM), FLT3 (4 nM), JAK1 (26 nM), JAK3 (39 nM).

HER2-IN-7 is a potent HER2 inhibitor with potential for researching ErbB-related diseases, especially cancer.