Angiogénesis

<p>CLM3, a pyrazolopyrimidine derivative, functions as a multitargeted tyrosine kinase inhibitor. It exhibits antiproliferative and proapoptotic activities on endothelial and cancer cells, activities that are synergistically enhanced by SN38. The primary mechanism of action for CLM3 involves the inhibition of phosphorylation in tyrosine kinases such as VEGFR-2, EGFR, and RET, along with their associated signaling pathways.</p>

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

<p>Multi-kinase inhibitor 3 (compound 12) is an orally active and effective multikinase (multikinase) inhibitor, demonstrating potent IC50 values against FLT1/VEGFR1, KDR/VEGFR2, FLT4/VEGFR3, FLT3, PDGFRα, and PDGFRβ, at 1.59, 1.23, 1.19, 0.59, 0.22, and 1.15 nM respectively. This compound exhibits anti-proliferative and anticancer activities.</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>Hypothemycin, a fungal polyketide, inhibits multiple kinases (VEGFR, MEK, FLT-3, PDGFR, ERK) with Kis ranging from 10 nM to 2.4 μM.</p>

<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>

<p>EGFR-IN-35, an acrylamide-based EGFR inhibitor, shows promise for EGFR mutation-related cancers like NSCLC.</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>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>

<p>FAK-IN-4 (Compound 7d) has anticancer activities that can induce cell apoptosis. FAK-IN-4 is potential inhibitor of FAK [1].</p>

<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.</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>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>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>

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

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>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>HER2-IN-7 is a potent HER2 inhibitor with potential for researching ErbB-related diseases, especially cancer.</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>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>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>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>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>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>Lirucitinib is a JAK inhibitor known for its anti-inflammatory properties.</p>

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

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

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

<p>EGFR-IN-17: potent, selective EGFR inhibitor, IC50 of 0.2 nM, overcomes C797S drug resistance.</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>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>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>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>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>VEGFR-2-IN-10 has enhanced antiangiogenic potency against VEGFR2 phosphorylation induced by VEGF with an IC50 value of 0.7 μM and no cytotoxic effects.</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>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>Tyk2-IN-3 is an inhibitor of Tyk2 pseudokinase (IC50: 485 nM).</p>

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

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

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

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

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>NDI-034858 (TAK-279) is a tyrosine kinase 2 (TYK2) inhibitor (Kd&lt;200 pM) that targets the JH2 structural domain of Tyk2 for the treatment of autoimmune diseases</p>

JAK2-IN-7 selectively inhibits JAK2 (IC50: 3 nM), shows 14-fold selectivity over JAK1/3, FLT3, induces G0/G1 arrest, apoptosis, and has antitumor effects.

<p>XMD-17-51 Trifluoroacetate is a pyrimido-diazepinone compound that regulates protein kinases.</p>

<p>JDTic, a 4-phenylpiperidine derivative distantly related to analgesics like meperidine and ketobemidone and more closely to the mu opioid antagonist alvimopan, exhibits a notably long duration of action, maintaining effects in animals for weeks following a single dose. This duration is not due to irreversible binding to the kappa opioid receptor but rather to altered activity of c-Jun N-terminal kinases. As a highly selective antagonist for the κ-opioid receptor, without influencing the μ- or δ-opioid receptors, JDTic has shown potential in animal studies for producing antidepressant and anxiolytic effects. It also demonstrates promise in treating addiction to substances such as cocaine and morphine, distinguishing itself structurally from other kappa antagonists like norbinaltorphimine.</p>

Ibrutinib is a selective, irreversible Btk inhibitor (IC50: 0.5 nM). Ibrutinib Racemate is the racemate of Ibrutinib.

<p>ENMD-2076 is an orally active kinase inhibitor. It also has antiangiogenic and antiproliferative mechanisms of action.</p>

<p>Nimotuzumab (powder) is a humanized IgG1 monoclonal antibody that specifically targets the epidermal growth factor receptor (EGFR), possessing a dissociation constant (KD) of 0.21 nM. It blocks the binding to its ligand by targeting the extracellular domain of EGFR. Nimotuzumab exhibits strong antitumor activity by inducing both antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), exerting cytolytic effects on target tumors.</p>

<p>PCI 45227 is an active metabolite of the Bruton's tyrosine kinase inhibitor ibrutinib .1PCI 45227 is formed from ibrutinib by the cytochrome P450 (CYP) isoform CYP3A.<br>1.Veeraraghavan, S., Viswanadha, S., Thappali, S., et al.Simultaneous quantification of lenalidomide, ibrutinib and its active metabolite PCI-45227 in rat plasma by LC-MS/MS: Application to a pharmacokinetic studyJ. Pharm. Biomed. Anal.107151-158(2015)</p>

<p>XMU-MP-3 is a robust, non-covalent inhibitor of BTK, exhibiting exceptional potency with IC50 values of 10.7 nM and 17.0 nM for BTK WT and BTK C481S mutation, respectively, in the presence of 10 μM ATP. Moreover, XMU-MP-3 elicits apoptosis.</p>

<p>Tyrosine-protein kinase ABL, IC50: 1500 nM</p>

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

<p>HMBD-001 is a humanized IgG1 monoclonal antibody inhibitor that targets HER3. By inhibiting the dimerization of HER3, HMBD-001 suppresses the growth and proliferation of tumor cells. It holds potential for research in cancer treatments, specifically for pancreatic cancer and non-small cell lung cancer.</p>

<p>PM-8002 is a bispecific antibody that targets PD-L1 and VEGF-A. It is applicable for research on solid tumors.</p>

<p>Desidustat is an inhibitor of HIF hydroxylase.</p>

<p>Duligotuzumab (MEHD-7945A) is a bispecific humanised IgG-κ monoclonal antibody targeting HER3 and EGFR, solid tumours, head and neck cancer,colorectal cancer.</p>

<p>Applications 3,3',4,4'-Tetrabromobiphenyl is multi-persistent organic pollutants analyzed in breast milk of first time mothers. An environmental pollutant that affects copper and molybdenum metabolism in rats. Also, it is derived from 1-Bromo-2- nitrobenze (B686175), which is an organic building block used for the synthesis of various pharmaceutical compounds. It is an intermediate for the synthesis of novel Diarylamino-1,3,5-triazine derivatives as FAK inhibitors with anti-angiogenic activity.<br>References Tlustos, C., et al.: Organohalogen Compd., 75, 1185-1188 (2013); Salman, K. N., et al.: Environ. Sci. Pollut. R., 21, 6400-6409 (2014); Dao, P., et al.: Bioorg. Med. Chem. Lett., 23, 4552 (2013);<br></p>

<p>KBP-7018: potent tyrosine kinase inhibitor targeting c-KIT, RET, PDGFR with IC50s of 10, 7.6, 25nM.</p>

<p>VEGFR inhibitor</p>