Angiogénese

<p>AZ 12799734 is an orally active, selective and potent dual inhibitor of TGFBR1 and ALK5 with inhibitory effects on BMP and TGFβ for the study of tumours.</p>

<p>Cavutilide has antiarrhythmic activity, inhibits hERG K(+) channels, and can be used to study heart failure and persistent atrial fibrillation.</p>

<p>SB 203580 hydrochloride (Adezmapimod hydrochloride) is a p38 MAPK inhibitor that induces mitochondrial autophagy and cytosolic autophagy.</p>

<p>SB-505124 hydrochloride (SB505124 hydrochloride) is a TGF-β type I receptor (ALK4, ALK5, ALK7) inhibitor for the study of colorectal cancer.</p>

<p>CCT241161: oral pan-RAF inhibitor; IC50s: LCK (3 nM), CRAF (6), SRC (10), V600E-BRAF (15), BRAF (30); fights BRAF/NRAS melanomas, anti-proliferative.</p>

<p>Applications α-Eudesmol is an isomer of β-Eudesmol (E938600), a sesquiterpenoid known to induce neurite outgrowth. β-Eudesmol exhibits antiangiogenic activity.<br>References Obara, Y. et al.: J. Pharmacol. Exp . Ther., 30, 803 (2011); Tsuneki, H. et al.: Eur. J. Pharmacol., 512, 105 (2005);<br></p>

<p>Donafenib(Bay 43-9006 (D3)) is a deuterium-labeled Sorafenib which is a multikinase inhibitor(IC50s: 6 nM, 20 nM, and 22 nM for Raf-1, B-Raf, and VEGFR-3,</p>

<p>Impurity Clopidogrel Impurity B; Clopidogrel USP B; Clopidogrel USP Related Compound B<br>Applications Clopidogrel Related Compound B (Clopidogrel Impurity B; Clopidogrel USP B; Clopidogrel USP Related Compound B) is a tetrahydrothienopyridine as inhibitor of angiogenesis.<br>References Maffrand, J. P., et al.: Eur. J. Med. Chem., 9, 483 (1974), Thebault, J.J., et al.: Clin. Pharmacol. Ther., 18, 485 (1975),<br></p>

<p>Itacnosertib (TP-0184) is an orally available ACRV1 (ALK-2), FLT3 and JAK2 inhibitor that inhibits the growth of tumor cells,antitumor and antileukemic.</p>

<p>Applications Glycerol 1-Monobutyrate functions as a key regulatory molecule in angiogenic process.<br>References Dobson, D. E., et al.: Cell (Cambridge, MA, U. S.), 61, 223 (1990)<br></p>

<p>Syk inhibitor II, a cell-permeable, ATP-competitive, pyrimidine-carboxamide compound, selectively and reversibly inhibits Syk (IC50 = 41 nM).</p>

<p>BIBF 1202 is a VEGFR2 kinase inhibitor (IC50 = 62 nM).</p>

<p>Canertinib dihydrochloride (PD-183805 dihydrochloride) is the hydrochloride salt of an orally bio-available quinazoline with potential antineoplastic and</p>

<p>BMS-690514 is a potent and orally active inhibitor of EGFR and VEGFR. It has IC50s of 5, 20 and 60 nM for EGFR, HER 2 and HER 4, respectively.</p>

<p>Applications 5-[(4-Hydroxyphenyl)methylene]-2,4-thiazolidinedione is a 5-Benzylidene-2,4-thiazolidenedione derivative designed as inhibitors of angiogenesis targeting VEGFR-2. Also, it is an intermediate used in the synthesis of MSDC 0602 (M755420), which is an analogue of thiazolidinediones, exhibits low affinity for binding and activation of peroxisome proliferator-activated receptor γ (PPARγ). Thiazolidinediones are effective insulin-sensitizing drugs for treating various metabolic and inflammatory diseases.<br>References Bhanushali, U., et al.: Bioorg. Chem., 67, 139-147 (2016); Chen, Z., et al.: J. Biol. Chem. 287, 23537 (2012); Fukunaga, T., et al.: J. Bone Miner. Res., 30, 508 (2015)<br></p>

<p>Solrikitug,Anti-CRLF2 humanized IgG1κ monoclonal antibody.</p>

<p>Serclutamab, a humanized chimeric monoclonal antibody of the IgG1-κ isotype, selectively targets the epidermal growth factor receptor (EGFR).</p>

<p>Vanucizumab is a bispecific humanised monoclonal antibody that simultaneously inhibits the receptor interactions of VEGF-A and Angiopoietin-2 (Ang-2)</p>

<p>Zalutumumab is a high-affinity fully human monoclonal antibody ,the extracellular domain of the EGFR squamous cell carcinoma of the head and neck (SCCHN).</p>

<p>Futuximab, a chimeric monoclonal antibody, targets distinct epitopes on the epidermal growth factor receptor (EGFR), exhibiting antineoplastic activity [1].</p>

<p>Dilpacimab (ABT165) is a dual-variable antibody that targets DLL4 and VEGF pathways, showing potential in cancer research by blocking angiogenesis and Notch.</p>

<p>Anti-Mouse VEGFR-2 Antibody (DC101) is a rat-derived monoclonal antibody against mouse VEGFR2/KDR/Flk-1, serving as a mouse analogue of ramucirumab.</p>

<p>Imgatuzumab (RG 7160) is a humanized anti-EGFR monoclonal antibody and immunomodulator for cancer research.</p>

<p>Tovetumab (MEDI-575) is an anti-PDGFRα mAb inhibiting its signaling, in trials for glioblastoma and NSCLC.</p>

<p>Ivonescimab (AK112) is a PD-1/VEGF bispecific antibody with cancer immunotherapy and anti-angiogenic effects, NSCLC).</p>

<p>Bafisontamab (EMB-01) is a bispecific antibody that targets EGFR and cMET, displaying antitumor activity [1].</p>

<p>Izalontamab (SI-B001) is a bispecific EGFR/HER3 monoclonal antibody that binds to both EGFR×EGFR homodimers and EGFR×HER3 heterodimers.</p>

<p>Anbenitamab (KN-026) is a bispecific HER2 antibody for metastatic breast cancer research, blocking HER2 pathways and mediating ADCC.</p>

<p>Faricimab,Bispecific antibody targeting Ang-2/VEGF-A. Prevents retinal I/R injury. Improves vision in w-AMD, DME, RVO.</p>

<p>Fidasimtamab, a recombinant human IgG1 bispecific antibody, targets both HER2 and PD-1, bridging T cells and tumor cells to modulate immune responses.</p>

<p>Becotatug (JMT-101) is an IgG1 antibody that targets EGFR and can be conjugated to Afatinib and Osimertinib, functioning as a synthetic antibody-drug conjugate</p>

<p>Ponezumab (PF-04360365), a humanized IgG2 antibody, lowers Aβ in the CNS &amp; boosts mice memory. Used in Alzheimer's research.</p>

<p>Tarcocimab (OG1953) is a humanized IgG1 monoclonal antibody targeting VEGFA, researched for RVO and wet AMD.</p>

<p>Elgemtumab (LJM716) is a fully humanised monoclonal antibody targeting HER3/ERBB3, acting as an antagonist to block HER3/Akt phosphorylation antitumour.</p>

<p>Depatuxizumab is a humanised monoclonal antibody targeting EGFR with blood-brain barrier (BBB) permeability, inhibit tumor growth,GBM,SCCHN.</p>

<p>Zanidatamab (ZW25) is a bispecific, humanized monoclonal antibody that targets two distinct epitopes (ECD2 and ECD4) of the HER2 receptor, exhibiting anti-tumor</p>

<p>Ibrutinib D5 is a deuterium-labeled Ibrutinib. Ibrutinib is an irreversible Btk inhibitor.</p>

<p>Dasatinib D8 is deuterium-labeled dasatinib. Dasatinib is a dual Bcr-Abl and Src family tyrosine kinase inhibitor.</p>

<p>IGF-1Rmodulator 1 (Example 5) is an IGF-1R modulator featuring an EC50 of 0.29 μM (FGFR1), 0.25 μM (IGF1R), 0.34 μM (TrkA), and 0.39 μM (TrkB). This compound is useful in research on diseases characterized by impaired signaling of neurotrophic and/or other trophic factors, such as Alzheimer's disease.</p>

<p>AD1058 is a selective ATR inhibitor that crosses the blood-brain barrier with in vivo anticancer activity, used in the study of brain and CNS metastasis.</p>

<p>EGFR-IN-109 (compound 4), an EGFR inhibitor, displays IC 50 values of 25.8 nM for EGFR WT and 182.3 nM for EGFR T790M. This compound halts the growth of cancer cells at the G2/M phase and triggers both early and late apoptosis. It is applicable in cancer research [1].</p>

<p>HVH-2930 is an inhibitor of Heat Shock Protein 90 (HSP90). It suppresses the cell viability of BT474 (Trastuzumab sensitive) and JIMT-1 (Trastuzumab resistant) by downregulating HSP90 client proteins such as HER2, p-HER2, AKT, p-AKT, cyclin D1, and survivin, with IC50 values of 6.86 μM and 4.42 μM, respectively. Additionally, HVH-2930 demonstrates antitumor efficacy in a mouse model and exhibits favorable pharmacokinetic properties in vivo.</p>

<p>(3S,4S)-Tofacitinib, a less active enantiomer of tofacitinib, is a Janus kinases inhibitor.</p>

<p>MAPK-IN-2 (compound 3h) is an efficacious MAPK inhibitor with antineoplastic properties that significantly hinders proliferation across various cancer cell</p>

<p>Erlotinib: reversible inhibitor binding to ATP site of epidermal growth factor receptor.</p>

<p>GZD856 formic inhibits PDGFRα/β (IC50: 68.6, 136.6 nM) &amp; Bcr-Abl (IC50: 19.9, 15.4 nM), with antitumor properties.</p>

<p>ZM39923 is a JAK3 inhibitor (pIC50: 7.1). ZM39923 also effectively inhibits tissue transglutaminase (IC50: 10 nM).</p>

<p>ALK5-IN-79 (compound 57), an ALK inhibitor, exhibits anticancer activity by inhibiting the TGF-β1/SMAD signaling pathway. It effectively reduces the production of extracellular matrix (ECM) and collagen deposition. Moreover, ALK5-IN-79 demonstrates satisfactory pharmacokinetic (PK) properties and favorable in vivo tolerance.</p>

<p>EGFR-IN-117 (Compound 8h) exhibits inhibitory activity against EGFR mutations, specifically targeting the tumor environment and inducing apoptosis in cancer cells. This compound effectively inhibits the proliferation of H1975, PC-9, and mutant EGFR cells including BaF3-EGFRL858R/T790M/C797S and BaF3–C797S/Del19/T790M, with IC50 values of 13 nM, 19 nM, 1.2 nM, and 1.3 nM respectively. Additionally, EGFR-IN-117 demonstrates anti-tumor activity in mouse models.</p>

<p>Applications Tyrphostin AG 1478 is a potent and selective inhibitor of EGFR.<br></p>

<p>Applications 4-Fmoc-3(R)-morpholinecarboxylic Acid is used to prepare 125I-labeled morpholine-containing RGD ligand of αvβ3 integrin as angiogenesis imaging probe.<br>References Bianchini, F., et al.: J. Med. Chem., 55, 5024 (2012)<br></p>

<p>Applications 2-Chloro-N-[4-(1-cyanocyclopentyl)phenyl]-3-pyridinecarboxamide is an intermediate Apatinib 25-N-Oxide (A726160), a metabolite of the antiangiogenic agent and selective VEGFR2 inhibitor Apatinib (A726150).<br></p>

<p>Applications Tyrphostin AG 112 is an EGFR inhibitor.<br></p>

<p>Applications 6-Amino-4-((3-chloro-4-(pyridin-2-ylmethoxy)phenyl)amino)-7-ethoxyquinoline-3-carbonitrile, is used in the synthetic preparation of aminopropanamides which is used in irreversible inhibition of epidermal growth factor receptor (EGFR) for potential use in cancer therapy.<br>References Carmi, C., et al.: J. Med. Chem., 55, 2251 (2012)<br></p>

<p>Applications LB 42708 is a selective nonpeptidic Farnesyltransferase (FTase) inhibitor.LB42708 suppresses tumor growth and tumor angiogenesis in both xenograft tumor models of Ras-mutated HCT116 cells and its wild-type Caco-2 cells, indicating its potential application in the treatment of both Ras-mutated and wild type tumors.<br>References Kim, C., et. al.: Mol. Pharmacol., 78, 142 (2010)<br></p>

<p>Applications Pulsatilla Saponin D shows antiangiogenic and antitumor activity.<br>References Sang-Won, H. et al.: Carcinogen., 34, 2156 (2013);<br></p>

<p>Applications Atrasentan is a selective antagonist of the endothelin-A (ETA) receptor and binds selectively to the ETA receptor, which may result in inhibition of endothelin-induced angiogenesis and tumor cell proliferation.<br>References Bax, W., et al.: Trends Pharmacol. Sci., 15, 379 (1994); Winn, M., et al.: J. Med. Chem., 39, 1039 (1996); Wu-Wong, J., et al.: J. Pharmacol. Exp. Ther., 281, 791 (1997);<br></p>

<p>Stability Moisture Sensitive<br>Applications 2,3-Naphthalic anhydride is used as a reagent to synthesize analogues of Thalidomide (T338850), an inhibitor of tumour necrosis factor that was once abandoned because it caused birth defects, but is currently used as an inhibitor of angiogenesis in patients with multiple myeloma.<br>References D’Amato, R., et al.: Proc. Nat. Acad. Sci., 91, 4082 (1994); Ehrenpreis, E., et al.: Gastroenterology, 117, 1271 (1999); Parma, T., et al.: Nat. Med., 5, 582 (1999); Singhal, S., et al.: New Engl. J. Med., 341, 1565 (1999)<br></p>

<p>Bucillamine (DE019) protects against Ischemia/reperfusion injury in high-risk organ transplants and inhibits the production of VEGF.</p>

<p>E3330 is a potent and selective APE1(Ref-1) inhibitor, which suppressed NF-kappa B DNA-binding activity.</p>

<p>TUL01101, a selective oral JAK1 inhibitor (IC50: 3 nM), also targets JAK2, JAK3, TYK2; for rheumatoid arthritis research.</p>

<p>BGB659 is effective inhibitor of RAF.</p>

<p>KRCA-0713 is a ALK inhibitor.</p>

<p>EGFR-IN-53 (Compound 7) is a potent inhibitor of EGFR (IC50 = 8.264 μM) that exhibits cytotoxic activity against cancer cell lines [1].</p>

<p>Peficitinib hydrobromide is used in the treatment of Psoriasis and Rheumatoid Arthritis.</p>

<p>CAY10717 inhibits 34/104 kinases at 100 nM, targets EGFR/ABL/B-Raf mutations, kills various cancer cells, and blocks HUVEC growth.</p>

<p>HP1328: potent FLT3/ITD inhibitor, reduces leukemia, extends survival in mice, belongs to benzoimidazole family.</p>

<p>Thi-DPPY: Potent JAK3/BTK inhibitor (IC50: 1.38/62.4 nM), anti-proliferative, anti-inflammatory, potential in IPF research.</p>

<p>TG53 is a tissue transglutaminase (TG2) and fibronectin (FN) protein-protein interaction inhibitor.</p>

<p>FLT3-IN-17: FAK inhibitor, IC50 of 12 nM; blocks CYPs, FLT3 mutants; IC50 &lt;0.5 nM for D835Y in cancer studies.</p>

<p>JG26 is a potent inhibitor of ADAM17, which can inhibit ADAM8, ADAM17, ADAM10 and MMP-12, with IC50 values of 12 nM, 1.9 nM, 150 nM and 9.4 nM, respectively,</p>

<p>GW837016X, also known as NEU-391, is a potent inhibitor of protozoan parasite proliferation.</p>

<p>YLT192 is an orally active and bioavailable VEGFR2 inhibitor. It also has potent antiangiogenic activity and antitumor efficacy.</p>

<p>c-Met-IN-11 is a potent inhibitor of c-MET (IC50: 41.4 nM) and VEGFR-2 (IC50: 71.1 nM).</p>

<p>LS-104 is a JAK2 inhibitor.</p>

<p>FGFR-IN-9: oral FGFR inhibitor, IC50: 17.1 nM (FGFR4 WT), 29.6 (FGFR3), 30.7 (V550L), 46.7 (FGFR2), 64.3 nM (FGFR1).</p>

<p>AP 24149, a potent dual inhibitor targeting Src and Abl, exhibits IC50 values of 9.1 nM for Src and 3.6 nM for Abl, respectively.</p>

<p>EGFR-IN-28 is a potent EGFR inhibitor. EGFR-IN-28 has antitumor activity .</p>

<p>BLK degrader 1 is a BLK degrader with anticancer activity for cancer research.</p>

<p>LRRK2/NUAK1/TYK2-IN-1 inhibits LRRK2, TYK2, NUAK1 with IC50 &lt; 10 nM, useful in autoimmune research.</p>

<p>Tyrphostin AG 568 promotes Tyrphostin-induced inhibition of p210bcr-abl tyrosine kinase activity. It also induces K562 to differentiate.</p>

<p>TL02-59 dihydrochloride is an orally active inhibitor of Src-family kinase Fgr (IC50: 0.03 nM).</p>

<p>WB-308 is an EGFR inhibitor that acts by decreasing NSCLC cell proliferation and colony formation and causing G2/M arrest and apoptosis.</p>

<p>VEGFR-2-IN-28 is a potent inhibitor of VEGFR-2 (IC50: 0.83 μM). VEGFR-2-IN-28 induces apoptosis and exhibits antitumor effects.</p>

<p>Momelotinib Mesylate is an ATP-competitive JAK1/JAK2 inhibitor (IC50: 11 nM/18 nM). It has 10-fold selectivity versus JAK3.</p>

<p>Selective inhibitor of Syk kinase</p>

<p>FAK/aurora kinase-IN-1, a dual inhibitor of FAK and aurora kinase, has IC50 values of 6.61 nM and 0.91 nM respectively, and demonstrates anticancer effects (WO2018019252A1; compound 11) [1].</p>

<p>FGFR3-IN-5: potent, selective FGFR3 inhibitor. IC50: 3 nM FGFR3, 44 nM FGFR2, 289 nM FGFR1. For cancer research.</p>

<p>S116836 is a tyrosine kinase inhibitor.</p>

<p>DS21360717 is an effective oral tyrosine kinase inhibitor with anticancer activity and IC50 of 0.49 nM.</p>

<p>Orally active Multi-kinase-IN-2 blocks angiokinases including VEGFR, PDGFR, FGFR, and more, reducing AKT/ERK phosphorylation and promoting apoptosis.</p>

<p>FAK inhibitor 5 is a novel allosteric FAK inhibitor, with IC50 values in the low micromolar range.</p>

<p>SB-220025 trihydrochloride is an effective and specific human p38 mitogen-activated protein kinase inhibitor.</p>

<p>PDGFRα/FLT3-ITD-IN-2 is a potent inhibitor of PDGFRα (IC50&gt;20 μM) and FLT3 (IC50: 0.004 μM).</p>

<p>PD173952 is a Src kinase and Myt1 inhibitor with antitumor activity, inhibits Lyn, Abl and Csk, and induces Bcr-Abl-dependent hematopoietic cell apoptosis.</p>

<p>YH-306 (TRV055 acetate ) is a modulator of the FAK signaling pathway that acts by suppressing colorectal tumor growth and metastasis.</p>