Angiogenesis

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

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

<p>Faricimab,Bispecific antibody targeting Ang-2/VEGF-A. Prevents retinal I/R injury. Improves vision in w-AMD, DME, RVO.</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>Solrikitug,Anti-CRLF2 humanized IgG1κ monoclonal antibody.</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>Ivonescimab (AK112) is a PD-1/VEGF bispecific antibody with cancer immunotherapy and anti-angiogenic effects, NSCLC).</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>Izalontamab (SI-B001) is a bispecific EGFR/HER3 monoclonal antibody that binds to both EGFR×EGFR homodimers and EGFR×HER3 heterodimers.</p>

<p>Tovetumab (MEDI-575) is an anti-PDGFRα mAb inhibiting its signaling, in trials for glioblastoma and NSCLC.</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>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>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>Elgemtumab (LJM716) is a fully humanised monoclonal antibody targeting HER3/ERBB3, acting as an antagonist to block HER3/Akt phosphorylation antitumour.</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>Tarcocimab (OG1953) is a humanized IgG1 monoclonal antibody targeting VEGFA, researched for RVO and wet AMD.</p>

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

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

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

<p>Anbenitamab (KN-026) is a bispecific HER2 antibody for metastatic breast cancer research, blocking HER2 pathways and mediating ADCC.</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>Erlotinib: reversible inhibitor binding to ATP site of epidermal growth factor receptor.</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>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>(3S,4S)-Tofacitinib, a less active enantiomer of tofacitinib, is a Janus kinases inhibitor.</p>

<p>ZM39923 is a JAK3 inhibitor (pIC50: 7.1). ZM39923 also effectively inhibits tissue transglutaminase (IC50: 10 nM).</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>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>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>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>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>Applications Tyrphostin AG 1478 is a potent and selective inhibitor of EGFR.<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 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 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>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 Tyrphostin AG 112 is an EGFR inhibitor.<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>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>