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>

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

<p>TGFBR1-IN-1 is an inhibitor of ALK5 (IC50 of 10-100 nM).</p>

<p>Antiproliferative agent-30 (Compound 8g) demonstrates broad-spectrum antiproliferative activity, with IC50 values of 0.054 nM, 0.008 nM, and 0.144 nM against</p>

<p>BTK-IN-24 is a Bruton's tyrosine kinase (BTK) inhibitor with potential anticancer activity, and it can be used in the study of myeloproliferative disorders.</p>

<p>THS-044 (N-[2-Nitro-4-(Trifluoromethyl)phenyl]morpholin-4-Amine) binding stabilizes the HIF2α PAS-B folded state with a kd of 2 μM and regulates HIF2 activity</p>

<p>PDGFRβ inhibitor</p>

<p>EGFR-IN-68, an EGFR inhibitor, has an IC50 of 0.33 μM and shows significant anticancer effects.</p>

<p>FM19G11 is an inhibitor of hypoxia inducible factor (HIF) α-subunit (IC50 = 80 nM in hypoxia induced luciferase assay).</p>

<p>BKI-1369 is a bumped kinase inhibitor. BKI-1369 increases hERG-inhibitory activity (IC50:1.52 μM).</p>

<p>ACP-5862, active metabolite of Acalabrutinib, is a BTK inhibitor with an IC50 of 5.0 nM.</p>

<p>NSC114126 is a potent, oral EGFR-TK inhibitor with strong antiproliferative effects, promising for cancer research.</p>

<p>EGFR-IN-50, a potent EGFR blocker, hinders L858R mutation; GI50: 8 nM for TEL-EGFR-L858R, 6.03 μM for T790M-L858R; curbs cancer cell growth.</p>

<p>FLT3-IN-15 is an orally active and potent FLT3 inhibitor, capable of acting on FLT3 (IC50: 0.87 nM) and FLT3/D835Y (IC50: 0.32 nM).</p>

<p>ALK5-IN-30 (EX-07) is a potent inhibitor of ALK with inhibitory effects on ALK5 (IC50&lt; 10 nM) and TGFβ-R1 (IC50&lt; 10 nM).</p>

<p>(Z)-Tyrphostin A51, a Z-isomer of Lanoconazole A51, is a strong PTK inhibitor blocking [3 H]taurine release and tyrosyl phosphorylation.</p>

<p>NSC81111 shows anticaner effects which is a potent and orally active inhibitor of EGFR-TK (IC50 = 0.15 nM) [1].</p>

<p>Naphazoline (Naphcon-a) is a sympathomimetic compound with marked alpha adrenergic activity.</p>

<p>CJ-2360 is a potent ALK inhibitor, effective on wild-type and various mutants, with IC50 values ranging from 2.2 to 8.9 nM, also targeting 468 kinases.</p>

<p>SJF620 is a potent degrader of PROTAC BTK(DC50 : 7.9 nM).</p>

<p>Flonoltinib (JAK2/FLT3-IN-1) is an orally active and efficient JAK2/FLT3 inhibitor with anti-cancer properties.</p>

<p>J-1048, an activin receptor-like kinase 5 (ALK5) inhibitor, effectively suppresses TAA-induced liver fibrosis in mice through specific inhibition of the TGF-β/</p>

<p>BTK inhibitor 10, an oral drug from patent WO2018145525, may treat rheumatoid arthritis.</p>

<p>Peficitinib HCl (ASP015K) is an oral JAK inhibitor with IC50s: JAK1 (3.9 nM), JAK2 (5.0 nM), JAK3 (0.7 nM), Tyk2 (4.8 nM).</p>

<p>JAK-IN-20: potent oral JAK1,2,3 inhibitor with IC50s 7, 5, 14 nM respectively, good pharmacokinetics, anti-inflammatory in vivo.</p>

<p>TX-1918, a tyrphostin, blocks eEF-2K to hinder HepG2, HCT116 cell growth.</p>

<p>TK4b, a JAK inhibitor, targets leukemia/lymphoid diseases, with IC50s: 18.42 nM (JAK3) &amp; 19.40 nM (JAK2).</p>

<p>FLT3/ITD-IN-2: Powerful FLT3/ITD, FLT3D835Y, and FLT3 inhibitor; hinders AML cell growth. IC50s: 0.3-1.0 nM.</p>

<p>KL-1156 is an NF-κB inhibitor. It is also a lipopolysaccharide (LPS)-induced nitric oxide production inhibitor.</p>

<p>DB07107 is a potent inhibitor of drug resistant T315I mutant Bcr-Abl tyrosine kinase and a potent Akt1 inhibitor (IC50: 360 nM).</p>

<p>PD180970 is an inhibitor of Bcr-Abl with IC50s of 5 nM, 0.8 nM and 50 nM for the autophosphorylation of p210Bcr-Abl, Src and Kit.</p>

<p>T338C Src-IN-2: Potent c-Src T338C kinase inhibitor; IC50: 317 nM, T338C/V323A: 57 nM, T338C/V323S: 19 nM.</p>

<p>TK4g, a potent JAK inhibitor, has IC50s of 12.61 nM (JAK2) &amp; 15.80 nM (JAK3); promising for lymphoid diseases &amp; leukemia research.</p>

<p>EGFR-IN-67 (Compound 7d) is a potent inhibitor of EGFR with anticancer activity (IC 50 = 0.34 μM) [1].</p>

<p>Squarunkin A HCl inhibits UNC119-cargo binding, specifically blocks Src kinase activation, IC50=10 nm.</p>

<p>JAK-2/3-IN-2 (Compound 3h) is a potent JAK2 &amp; JAK3 inhibitor with IC50s of 23.85 nM (JAK2) &amp; 18.9 nM (JAK3).</p>

<p>JNJ-47117096 hydrochloride is potent and selective MELK inhibitor, with an IC50 of 23 nM, also effectively inhibits Flt3, with an IC50 of 18 nM.</p>

<p>C-ABL-IN-2 is a potent c-Abl protein inhibitor, promising for research in cancer and neurodegenerative diseases like ALS and PD.</p>

<p>MS 154N is a negative control for MS 154, binds WT/L858R EGFR tightly (Kd 3-4.3nM), doesn't trigger mutant EGFR degradation.</p>

<p>Famitinib (SHR1020), an oral drug, inhibits c-kit, VEGFR-2, and PDGFRβ (IC50: 2.3/4.7/6.6 nM) and triggers apoptosis in gastric cancer.</p>

<p>OD36 hydrochloride (OD-36 hydrochloride) is a potent RIPK2 inhibitor with an IC50 of 5.3 nM.OD36 hydrochloride is a macrocyclic inhibitor that binds efficiently</p>

<p>TYK2-IN-12: selective oral TYK2 inhibitor (Ki: 0.51 nM), blocks IL-12-induced IFNγ; IC50: human 2.7 µM, mouse 7.0 µM, used for psoriasis research.</p>

<p>PDE5-IN-3: Inhibits PDE5 (1.57 nM), EGFR (5.827 μM), Wnt pathway (1286.96 ng/mL), induces apoptosis, and has antitumor effects.</p>

<p>PDGFR-IN-1 is a platelet-derived growth factor receptor (PDGFR) inhibitor, strongly inhibiting PDGFRα and PDGFRβ, useful for studying solid tumors.</p>

<p>IHMT-TRK-284: Oral type II TRK inhibitor; targets TRKA, TRKB, TRKC (IC50s: 10.5, 0.7, 2.6 nM); selective and anti-tumor effective.</p>

<p>FGFR3-IN-2 (compound 18b) is a potent and selective FGFR3 inhibitor that inhibits FGFR3 (IC50: 4.1 nM) and VEGFR2 (IC50: 570 nM).</p>

<p>CpCDPK1/TgCDPK1-IN-1 is a inhibitor of CpCDPK1 and TgCDPK1, inhibits Abl and Src, and has antiparasitic activity for the study of Toxoplasma infections.</p>

<p>AG 370, an indole tyrphostin, functions as a powerful inhibitor of PDGF-induced mitogenesis, demonstrating an IC50 of 20 μM.</p>