Angiogénese

<p>EGFR-IN-71 is a potent inhibitor of epidermal growth factor receptor (EGFR) (IC50= 3.7 μM). EGFR-IN-71 has research value in chordoma.</p>

<p>Pan kinase inhibitor</p>

<p>FGFR-IN-8, potent oral FGFR inhibitor for wild-type/mutant types, induces apoptosis with anti-cancer properties.</p>

<p>Henatinib: orally active multi-kinase inhibitor targeting VEGFR-2, c-kit, PDGFR with antitumor effects.</p>

<p>CHMFL-FLT3-122 is a potent and orally available FLT3 kinase inhibitor used to treat FLT3-ITD positive acute myeloid leukemia.</p>

<p>MS 154 is a potent PROTAC® targeting mutant EGFR in lung cancer, sparing WT-EGFR; effective in mice, with DC50 of 11-25 nM.</p>

<p>EGFR-IN-33, a low-toxicity acrylamide, inhibits EGFR, aiding against cancer, especially NSCLC (from WO2021185348A1, comp. 13).</p>

<p>GSK2646264 (Compound 44) inhibits SYK (pIC50=7.1) and kinases like LCK, LRRK2; penetrates skin.</p>

<p>Larixol acts as both an fMLP inhibitor and a modulator of various signaling pathways by inhibiting Src kinase, ERK1/2, p38, and AKT phosphorylation critical for</p>

<p>PF-06459988 is a novel, effective, orally active, irreversible, and selective epidermal growth factor receptor (EGFR) mutant inhibitor.</p>

<p>Sevabertinib (BAY 2927088) is an EGFR tyrosine kinase inhibitor, with anticancer activity, used in research on non-small cell lung cancer.</p>

<p>ALK2-IN-4, a highly effective ALK2 inhibitor.</p>

<p>IN-1130: ALK5 inhibitor, IC50 - 5.3 nM (Smad3), 36 nM (casein), 4.3 μM (p38α MAPK).</p>

<p>BMS-935177 is a reversible BTK inhibitor with IC50 value of 3 nM.</p>

EGFR-IN-87 is an EGFR tyrosine kinase inhibitor with potent inhibitory activity, exhibiting IC50 values of 3.1 nM, 1.3 nM, and 7.1 nM against EGFR_d746-750,

<p>Zongertinib is a human HER2-selective tyrosine kinase inhibitor, a novel TK that is highly selective for covalent binding to the HER2 tyrosine kinase domain (</p>

<p>HM43239: oral FLT3 inhibitor; IC50: FLT3 WT 1.1nM, ITD 1.8nM, D835Y 1.0nM; blocks p-STAT5/p-ERK; affects SYK, JAK1/2, TAK1; halts leukemia cell growth.</p>

<p>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>

<p>MM-589 is a potent WD repeat domain 5 (WDR5) inhibitor and mixed lineage leukemia (MLL) protein-protein interaction.</p>

<p>Lomonitinib is a potent and selective pan-FLT3/IRAK4 inhibitor with antitumor properties. It shows promise for research in myeloid leukemia.</p>

<p>EGFR-IN-146 is an EGFR inhibitor that suppresses the EGFR signaling pathway and improves insulin sensitivity by activating the AMPK pathway. It effectively reduces blood glucose levels and body weight, showing great potential in the study of diabetes and obesity.</p>

<p>MTX-216 is an ATP-competitive inhibitor targeting both PI3K and EGFR. It simultaneously inhibits Ki-67 and ribosomal S6 phosphorylation, inducing apoptosis in NF1LOF cells. Additionally, MTX-216 suppresses SYK kinase activity with an IC50 of 281 nM. This compound is applicable for melanoma research.</p>

<p>BMS-986143: oral BTK inhibitor, IC50=0.26 nM, potential for autoimmune research, also targets TEC, BLK, BMX, TXK, YES1, ITK.</p>

<p>JAK3/BTK-IN-4, a dual inhibitor for JAK3/BTK, shows synergy in autoimmune disease treatment. (Patent WO2021147953A1, compound 003)</p>

<p>FLT3-IN-13 inhibits topoisomerase II/FLT3 in leukemia with IC50 of 2.26 μM, causes G2/M arrest, and promotes apoptosis.</p>

<p>FLT3/ITD-IN-1 inhibits FLT3-ITD with IC50s: 38.2 nM (FLT3) and 144.1 nM (ITD), and fights acute myeloid leukemia.</p>

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

<p>BML-265 is a potent inhibitor of EGFR tyrosine kinase (EGFR tyrosine kinase). It disrupts Golgi apparatus integrity in human cells and hinders the transport of secretory proteins across various substances. In contrast, BML-265 does not affect the integrity and transport of the Golgi apparatus in rodent cells.</p>

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>VEGFR-2-IN-11 is a potent inhibitor of VEGFR-2 (IC50: 60.27 nM) with an IC50 value of 60.27 nM, which induces apoptosis and has anticancer activity.</p>

<p>ERBB agonist-1 (Compound EF-1) is an ERBB4 agonist that activates the ERBB4 signaling pathway by inducing ERBB4 receptor dimerization, with an EC50 of 10.5 μM. It promotes phosphorylation of Akt and ERK1/2, reduces collagen expression in cardiac fibroblasts, and inhibits H2O2-induced cardiomyocyte death and Ang II-induced cardiac hypertrophy. Furthermore, ERBB agonist-1 can prevent myocardial fibrosis and demonstrates cardioprotective effects in mouse models.</p>

<p>FAK-IN-26 is a blood-brain barrier-penetrating inhibitor of Focal Adhesion Kinase (FAK) with an IC50 of 0.87 nM. It significantly reduces tumor cell viability, cancer stem cell activity, and cell migration in A549 and SKOV-3 cell lines. FAK-IN-26 exhibits potent anticancer activity, achieving tumor inhibition rates of 59.15% and 57.9% in A549 and SKOV-3 tumor mouse models, respectively.</p>

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

<p>(-)-Cevimeline HCl hemihydrate, a muscarinic agonist, treats Sjogren's xerostomia. Quick absorption, species-dependent metabolism.</p>

<p>Tyk2-IN-3 is an inhibitor of Tyk2 pseudokinase (IC50: 485 nM).</p>

<p>(3S,4R)-Tofacitinib is an less active enantiomer of Tofacitinib. Tofacitinib is a JAK3 inhibitor(IC50 : 1 nM).</p>

<p>VEGFR-2-IN-16 (Compound 15b) is a potent inhibitor of VEGFR-2 (IC50: 86.36 nM) that exhibits antitumour effects.</p>

<p>PF-06263276 selectively inhibits pan-JAK with IC50: JAK1 (2.2 nM), JAK2 (23.1 nM), JAK3 (59.9 nM), TYK2 (29.7 nM).</p>

<p>EGFR-IN-161 (Compound DD-8) is a potent and reversible inhibitor of the L858R/T790M/C797S mutant EGFR kinase, with an IC50 value of 0.87 nM. EGFR-IN-161 effectively inhibits tumor cell apoptosis, G1 phase arrest, and migration.</p>

<p>MM-589 TFA is a potent WD repeat domain 5 (WDR5)inhibitor and mixed lineage leukemia (MLL) protein-protein interaction.</p>

<p>W23-1006 is a selective covalent ALKBH5 inhibitor. It binds to the ALKBH5 C200 residue with an IC50 value of 3.848 μM. The inhibitory activity of W23-1006 is approximately 30 times stronger than that of FTO and 8 times greater than that of ALKBH3. W23-1006 is applicable for research in triple-negative breast cancer (TNBC).</p>

<p>Potent EGFR/HER2/DHFR inhibitor for MCF-7 breast cancer; IC50: 0.153/0.108/0.291 μM; arrests G1/S phase, triggers apoptosis.</p>

<p>Protein kinase inhibitor 11 (Compound I-96) is an agent that inhibits the activity of PIM-1, CDK-2, GSK-3, and SRC. It shows potential for research in cancer, autoimmune diseases, and neurodegenerative disorders.</p>

<p>JP-153 is an inhibitor of Src-FAK-Paxillin signaling. It suppresses Src-dependent phosphorylation of paxillin (Y118) and subsequent activation of Akt (S473). JP-153 reduces VEGF-induced migration and proliferation of retinal endothelial cells and is applicable in the study of neovascular eye diseases.</p>

<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>

<p>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.</p>

<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>

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

<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>

<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>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>

<p>FAK-IN-23 (Compound II) is an inhibitor of focal adhesion kinase (FAK).</p>

<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>

<p>HSN748 is an analog of ponatinib and acts as a multi-kinase inhibitor. It exhibits inhibitory activity against kinases such as FLT3, ABL1, RET, PDGFRα/β, MNK1, and MNK2. HSN748 can suppress the growth of chronic myeloid leukemia and acute myeloid leukemia cell lines, making it a useful compound in leukemia research.</p>

<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>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>

<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>FGFR4-IN-7 is a covalent, reversible FGFR4 inhibitor (IC50: 0.42 μM) that blocks the FGFR4 signaling pathway, thereby inducing apoptosis.</p>

<p>VEGFR-2-IN-13 (Compound 19a) is a potent VEGFR-2 inhibitor (IC50: 3.4 nM). vEGFR-2-IN-13 arrests the HepG2 cell cycle in G2/M phase and induces apoptosis.</p>

<p>EGFR-IN-44: potent EGFR kinase inhibitor, orally active, IC50 4.11 nM, 33.57% bioavailability, induces apoptosis, for lung cancer study.</p>

<p>DBMB is a spleen tyrosine kinase (Syk) inhibitor that significantly suppresses Syk enzyme activity. It possesses anti-inflammatory properties by inhibiting NF-κB signaling, thereby reducing the production of inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2). DBMB can be utilized in research on inflammatory diseases.</p>

<p>BTK-IN-8: potent, selective covalent BTK inhibitor; IC50=0.22 nM, Kd=0.91 nM; effective in blood CD69 cells (IC50=0.029 μM).</p>

<p>JBJ-02-112-05 is a potent, mutant-selective, allosteric and orally active inhibitor of EGFR with an IC 50 of 15 nM for EGFR L858R/T790M [1].</p>

<p>EGFR-IN-38: low-toxic acrylamide-derived EGFR inhibitor, targets NSCLC, patented for research on EGFR mutation-related diseases.</p>

<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>

<p>SJ-C1044 is an orally effective pan-RAF inhibitor demonstrating immunomodulatory and antitumor activities. It targets wild-type BRAF, wild-type CRAF, and BRAF(V600E) with IC50 values of 331, 257, and 187 nM, respectively. SJ-C1044 suppresses tumor cell proliferation by inhibiting kras activation and MEK-ERK phosphorylation. Additionally, it shows inhibition of VEGFR2, TIE2, and CSF1R, with IC50 values of 100, 23, and 235 nM respectively. The compound enhances the tumor immune microenvironment through inhibition of angiogenesis and modulation of macrophage function. SJ-C1044 is applicable for research in colorectal cancer.</p>

<p>Flonoltinib maleate is an orally active dual inhibitor of JAK2/FLT3, with IC50 values of 0.7 nM for JAK2, 4 nM for FLT3, 26 nM for JAK1, and 39 nM for JAK3. It exhibits anticancer properties.</p>

<p>TX2-121-1 targets HER3 for proteasome-mediated degradation to inhibit HER3-dependent signalling and growth.</p>

<p>CEP-14083: potent ALK inhibitor, effective in NPM/ALK T-cell lymphoma, binds ATP site; IC50=11 nmol/L, also inhibits insulin receptor, preclinical efficacy.</p>

<p>E6201, a dual kinase inhibitor, blocks MEK1/FLT3 and has anti-tumor/psoriasis effects with low IC50s: ERK2 (5.2 nM), JNK (91 nM), p38 MAPK (19 nM).</p>

<p>Paeoniflorin-6′-O-benzene sulfonate (CP-25) acts as an inhibitor of G protein-coupled receptor kinase 2 (GRK2), preventing its translocation to the cell membrane and inhibiting the JAK1/STAT3 signaling pathway. It suppresses HaCaT cell proliferation induced by IL-17A/CXCL2. In mouse models, CP-25 reduces the levels of inflammatory cytokines and chemokines such as IL-17A, IL-17F, IFN-γ, TNF-α, IL-22, IL-23, CXCL2, CXCL3, and CXCL9, thereby alleviating psoriasis induced by Imiquimod.</p>

<p>Protein kinase inhibitor 13 (Compound I-90) functions as a kinase inhibitor, specifically targeting kinases such as PIM-1, CDK-2, GSK-3, and SRC.</p>

<p>CGP062464 is an inhibitor of the tyrosine kinase c-Src, with an IC50 of less than 50 nM. It is utilized in research related to osteoporosis and tumor-induced hypercalcemia.</p>

<p>HER2-IN-8 is an inhibitor of HER-2 that can be used in the study of cancer and inflammation-related diseases.</p>

<p>Pyk2-IN-2 (compound 13j) acts as a Pyk2 inhibitor, exhibiting an IC 50 value of 0.608 μM for FAK kinase [1].</p>

<p>JAK3/BTK-IN-7 (XL-12), characterized as a JAK3/BTK inhibitor, exhibits IC 50 values of 2 nM and 14 nM for JAK3 and BTK respectively. This compound demonstrates anti-inflammatory properties and is applicable in research related to rheumatoid arthritis [1].</p>

<p>Brefeldin A 4-O-nicotinate (CHNQD-01228) is a dual inhibitor of Arf1 and BMX proteins with an IC50 value of 0.22 μM for T24 cell proliferation. It also suppresses T24 cell migration and colony formation in a dose-dependent manner, induces G1 phase arrest, and triggers apoptosis. By targeting BMX proteins, it inhibits the AKT/p-AKT and STAT3/p-STAT3 signaling pathways, while also inhibiting Arf1 proteins to eliminate bladder cancer stem cells and activate antitumor immunity, thus exhibiting anticancer activity. Brefeldin A 4-O-nicotinate is applicable in research related to bladder cancer.</p>

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

<p>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).</p>

<p>EG31 is an EGFR inhibitor that effectively suppresses the proliferation of triple-negative breast cancer (TNBC) cells by inhibiting the EGFR signaling pathway. It demonstrates a GI50 value of 498.90 nM for MDA-MB-231 cells and 740.73 nM for Hs578T cells, while also inducing apoptosis. Additionally, EG31 retains its antiproliferative activity against 5-fluorouracil (5-FU) resistant TNBC cells, with a GI50 of 519.5 nM. EG31 is applicable in research on TNBC resistance.</p>

<p>VEGFR-IN-3 inhibits cancer cell growth (OVCAR-4, MDA-MB-468) with IC50s: 0.29, 0.35μM. Used in cancer research.</p>

<p>HER2-IN-12 is an HER2 inhibitor with an IC50 value of 121 nM and can be used to study cancers such as breast cancer.</p>

<p>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.</p>

JAK/HDAC-IN-3 (13a), a dual inhibitor of JAK and HDAC, exhibits IC50 values of 25.36 nM for JAK2, 0.2 μM for HDAC, and 0.43 μM for HDAC1, respectively [1].

<p>Tyk2-IN-15 (Compound 97) is a selective inhibitor of tyrosine kinase 2 (Tyk2) with an IC50 value ≤ 10 nM for Tyk2-JH2. It is utilized in the research of inflammatory and autoimmune diseases [1].</p>

Tofacitinib Prodrug-1: an oral prodrug reducing Tofacitinib's side effects, treats ulcerative colitis in mice effectively with low toxicity.

<p>Tyk2-IN-14, a small molecule inhibitor of TYK2, is significant in treating inflammatory diseases and conditions linked to hypersecretion of IFNa and interferons [1].</p>

EGFR-IN-160 is an EGFR inhibitor with IC50 values of 1.62, 0.49, and 0.98 μM for EGFRWT, EGFRT790M, and EGFRL858R/T790M/C797S, respectively. It can induce cell cycle arrest at the G2/M and S phases and apoptosis (Apoptosis) in NCI-H522 cells, demonstrating anticancer properties. Additionally, EGFR-IN-160 exhibits antioxidant activity against DPPH (IC50: 12.11 µM) and H2O2 (IC50: 8.89 µM).

<p>JAK1/TYK2-IN-4 serves as a dual inhibitor targeting both JAK and TYK2, displaying IC50 values of 39 nM and 21 nM, respectively. It is also orally bioavailable [1].</p>

<p>Tyk2-IN-17 (compound 185) effectively inhibits TYK2 [1].</p>

<p>PNU-145156E is a noncytotoxic molecule inhibiting growth and angiogenic factors, suppress tumor angiogenesis, support anti-angiogenic research strategies.</p>

<p>Lazertinib (mesylate) (YH25448 (mesylate); GNS-1480 (mesylate)) is an orally active EGFR inhibitor capable of crossing the blood-brain barrier. It suppresses the p-EGFR, p-AKT, and p-ERK signaling pathways, leading to apoptosis. Lazertinib (mesylate) demonstrates antitumor activity in the H1975-luc BM xenograft model in mice and is applicable for researching non-small cell lung cancer.</p>

<p>EGFR-IN-47: strong oral EGFRL858R/T790M/C797S blocker, induces cell death; promising for NSCLC research. IC50: 0.01 μM.</p>

<p>VEGFR-2-IN-18 is a potent VEGFR-2 inhibitor with a 60 nM IC50, promoting cell apoptosis and anticancer effects.</p>