Angiogenesis

<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>

<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>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>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>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>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>FAK-IN-23 (Compound II) is an inhibitor of focal adhesion kinase (FAK).</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>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>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>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>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>FGFR2/3-IN-2 (compound 10) is an orally active inhibitor targeting FGFR2 and FGFR3. It exhibits IC50 values of 3.7 nM for FGFR2 and 31.2 nM for FGFR3, with a pre-incubation time of 1 hour. FGFR2/3-IN-2 demonstrates selectivity over FGFR1/4 and other kinases, and does not cause diarrhea or increased serum phosphate in vivo. In the SNU-16 gastric cancer model, FGFR2/3-IN-2 can induce tumor stasis or regression.</p>

<p>EGFR-IN-159 (compound 12) is a dihydropyrimidine and a potent EGFR inhibitor with an IC50 of 29.00 nM. It exhibits dose-dependent inhibition of EGFR and HER2. The compound shows cytotoxicity against MCF-7 breast cancer cells and Vero cells with IC50 values of 16.07 μg/mL and 35.98 μg/mL, respectively. EGFR-IN-159 does not cross the blood-brain barrier (BBB) and demonstrates significant anticancer activity.</p>

<p>Gamendazole is a novel drug candidate for male contraception. It has been shown to reduce fertility in male rats without affecting testosterone levels.</p>

<p>EGFR-IN-149 (Compound 3-OH) is an EGFR inhibitor with an IC50 value of 0.42 nM.</p>

<p>M-COPA disrupts Golgi, blocks MET &amp; Arf1 activation, and inhibits angiogenesis via VEGFR &amp; NF-kB pathways.</p>

<p>Clifutinib (Compound 9e) is an orally active, selective inhibitor of FMS-like tyrosine kinase 3 (FLT3-ITD) with an IC50 of 15.1 nM. It inhibits FLT3-ITD kinase activity and blocks downstream signaling pathways, including RAS/MAPK, PI3K/AKT, and JAK/STAT5. Clifutinib induces apoptosis in FLT3-ITD mutated acute myeloid leukemia (AML) cells and is a potential candidate for research in relapsed/refractory FLT3-ITD positive AML.</p>

<p>VEGFR-2/DHFR-IN-2 inhibits VEGFR-2 &amp; DHFR (IC50: 0.623 &amp; 9.085 μM), toxic to C26, HepG2, MCF7 cells (IC50: 3.59-8.38 μM), promising for cancer study.</p>

<p>VEGFR-2-IN-15 (Compound 14b) is a potent inhibitor of VEGFR-2. VEGFR-2-IN-15 inhibits the growth of HepG2 cells in the Pre-G1 phase and induces apoptosis.</p>

<p>FGFR1inhibitor-15 (Compound 23) is an FGFR1 inhibitor with an IC50 value of 27 μM, useful for tumor research.</p>

<p>VEGFR-2-IN-17 (15a) is a potent VEGFR-2 inhibitor with an IC50 of 67.25 nM, showing significant antitumor effects.</p>

<p>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.</p>

<p>BTK-IN-6, a potent BTK inhibitor, may treat immune, cardiac, cancer, viral, inflammatory, metabolic, and neurological disorders.</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>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>PP487 is a dual tyrosine kinase/PI(3)K inhibitor, exhibiting IC50 values of 0.017 μM, 0.072 μM, 0.004 μM, 0.01 μM, 0.55 μM, 0.22 μM, and &lt; 0.01 μM against DNA-PK, mTOR, Hck, Src, EGFR, EphB4, and PDGFR, respectively. It is applicable in cancer research [1].</p>

<p>"JAK-IN-23: oral dual JAK/STAT &amp; NF-κB inhibitor; JAK1 (IC50: 8.9 nM), JAK2 (15 nM), JAK3 (46.2 nM); for IBD research."</p>

<p>FGFR-IN-5 is a potent inhibitor of FGFR. FGFR-IN-5 has potential for research in cancer diseases.</p>

<p>EGFR-IN-35, an acrylamide-based EGFR inhibitor, shows promise for EGFR mutation-related cancers like NSCLC.</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>VEGFR-2-IN-12 (compound 6g), a 2-oxoquinoxalinyl-1,2,4-triazole, is a potent inhibitor of VEGFR-2 (IC50: 0.037 μM). VEGFR-2-IN-12 has anti-tumour effects.</p>

<p>CDDD11-8 is an orally administered, highly potent and selective CDK9 and FLT3-ITD inhibitor, with K i values of 8 nM and 13 nM, respectively. It effectively reduces the proliferation of leukemia cell lines, showing particular efficacy against those with the FLT3-ITD mutation [1] [2].</p>

<p>EGFR-IN-45: Strong EGFR/CDK2 inhibitor (IC50s: 0.4 &amp; 1.6 μM), halts cancer cell cycle pre-G1, prompts apoptosis, also targets Topo I/II.</p>

<p>Compound 8b inhibits VEGFR-2/DHFR, combats various bacteria, and fights cancer cells.</p>

<p>FLT3/TrKA-IN-1: Potent dual kinase inhibitor for FLT3 &amp; TrKA, promising for AML research.</p>

<p>DDO-02267 is a selective lysine-targeted covalent inhibitor of ALKBH5, with an IC50 value of 0.49 μM. It increases levels of N6-methyladenosine (m6A) and targets the ALKBH5-AXL signaling axis. DDO-02267 serves as a probe for studying the biological function of mRNA demethylases.</p>

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

<p>EGFR/HER2-IN-8 inhibits EGFR, HER2, DHFR (IC50: 0.45, 0.244, 5.669 μM); useful in cancer research, safe and selective.</p>

<p>VEGFR-2-IN-25 (compound 5d) is a potent inhibitor of VEGFR-2 (IC50: 12.1 nM).</p>

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

<p>Sacibertinib inhibits Trk, targeting EGFR-TK (EC50 110 nM) &amp; HER2 (EC50 244 nM), with anticancer properties.</p>

<p>EGFR-IN-34 is a low-toxicity, acrylamide derivative antitumor agent that is a potent inhibitor of EGFR.</p>

<p>HER2-IN-6, a potent HER2 inhibitor, may target wild/mutant EGFR and HER2-mediated tumors. (Patent WO2021164697A1, compound 11)</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>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>

<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>

<p>EGFR-IN-24 is a potent inhibitor of EGFR and inhibits EGFR (del19/T790M/C797S) and EGFR (L858R/T790M/C797S).</p>

<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>

<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>

<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>CEE321 is an effective pan-JAK inhibitor with an IC50 of 54 nM. It effectively inhibits biomarkers associated with atopic dermatitis.</p>

<p>BTK-IN-7 is a potent inhibitor for BTK with 4.0 nM IC50, highly selective over ITK and EGFR, showing strong antitumor activity.</p>

<p>Ki11502 is a multi-target receptor tyrosine kinase (RTK) inhibitor that selectively inhibits the activity of PDGFβ/α receptors (with an IC50 of less than 10 nM). It specifically suppresses PDGFβ receptor phosphorylation, proliferation, and proteoglycan synthesis in human vascular smooth muscle cells. Additionally, Ki11502 induces apoptosis and exhibits significant antiproliferative effects against specific leukemia subgroups, including those with Imatinib-resistant mutations. It is particularly suitable for studying the role of PDGF in vascular diseases and the involvement of proteoglycans in atherosclerosis.</p>

<p>EGFR/HER2-IN-6 is a dual inhibitor of EGFR, HER2, and DHFR with IC50s: 0.122, 0.078, and 0.585 μM, showing anticancer potential and selectivity.</p>

<p>FGFR4-IN-6: covalent, reversible FGFR4 blocker, 5.4 nM IC50, good oral bioavailability, reduces Hep3B2.1-7 tumors in mice, low toxicity.</p>

<p>FGFR4-IN-9 is a selective inhibitor of FGFR4 (IC50: 75.3 nM) that effectively inhibits the growth and angiogenesis of hepatocellular carcinoma cells.</p>

<p>EGFR-IN-17: potent, selective EGFR inhibitor, IC50 of 0.2 nM, overcomes C797S drug resistance.</p>

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

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

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

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

<p>EGFR-IN-18 strongly inhibits L858R/T790M/C797S mutant EGFR (4.9 nM) and also targets wild-type EGFR (47 nM).</p>

<p>EGFR-IN-62: IC50 of 10-242 nM for various EGFR mutations, blocks A549/H1975 cell cycle, induces apoptosis, and inhibits cell motility and proliferation.</p>

<p>PF-06463922 acetate: ALK/ROS1 inhibitor, brain- penetrable, active vs crizotinib-resistant mutants, in NSCLC trials.</p>

<p>FGFR1 inhibitor-6, IC50: 16.31 nM, blocks cell cycle at pro-G1/G2/M and induces apoptosis.</p>

<p>ALK-IN-23 inhibits ALK (IC50: 1.6-0.71 nM), hinders cancer cell spread, forms colonies in vitro, and reduces tumors in mice with low toxicity.</p>

<p>BTK-IN-10 is a potent inhibitor of BTK, acting on wild-type BTK (IC50&lt;5 nM) or mutant BTK (C481S) (IC50&lt;5 nM).</p>

<p>VEGFR-2-IN-14 (Compound 5) is a potent inhibitor of VEGFR-2, which inhibits the growth of HepG2 cells in the Pre-G1 phase and induces apoptosis.</p>

<p>NSC381467: Potent, oral EGFR-TK inhibitor with strong antiproliferative effects, promising for cancer research.</p>

<p>AZD0424: oral Src/Abl kinase inhibitor; potential anticancer; induces apoptosis, cell cycle arrest in lymphoma.</p>

<p>Ten01 exhibits a 5.0 nM inhibition of JAK1 kinase.</p>