Angiogenesis

EGFR-IN-136 (compound 21v) is a potent inhibitor of EGFR, demonstrating IC50 values of 20.2 nM, 1.2 nM, 2.3 nM, and 12.5 nM for EGFRWT, EGFRLR/TM, EGFR19D/TM/CS, and EGFRLR/TM/CS, respectively. It exhibits antiproliferative and antitumor activities and holds potential for research in non-small cell lung cancer (NSCLC).

Applications Isotope labelled 2-Methoxy-4-[2-[(1-methylethyl)amino]ethyl]phenol is an catecholamine based derivative with potential anti-angiogenic properties.

Ibuprofen, an NSAID, reduces pain, inflammation, and fever by limiting prostaglandin production.

R1530 is a multikinase inhibitor with antineoplastic and antiangiogenesis activities.

PD-161570 is a potent and ATP-competitive human FGF-1 receptor inhibitor with an IC50 of 39.9 nM and a Ki of 42 nM.

BW710 is an orally active inhibitor specifically targeting fibroblast growth factor receptor 2 (FGFR2). It effectively inhibits the proliferation of BaF3-FGFR2 cells with an IC50 value of 2.8 nM. BW710 completely suppresses FGFR2 enzymatic activity and demonstrates selectivity among 75 tyrosine kinases, including FGFR1, FGFR3, and FGFR4, at a 1 μM concentration. Additionally, BW710 impedes FGFR2 signaling and selectively inhibits the proliferation of cancer cells driven by FGFR2. It exhibits promising pharmacokinetic properties, with an oral bioavailability of 29% in mice.

Applications (4-Nitrophenyl)acetic Acid used in the synthesis of 5,7-dimethyl-2-aryl-3H-pyrrolizin-3-ones which may act as angiogenesis inhibitors. Also used in the one step construction of amino-substituted squaraine dye. References Kirk, N., et al.: Bioorg. Med. Chem. Lett., 26, 1813 (2016); Ying, H., et al.: Dyes Pigments, 131, 264 (2016);

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.

DualCathepsinL/JAK-IN-1 (Compound A8) serves as a dual inhibitor of Cathepsin L (CTSL) and JAK, exhibiting IC50 values of 0.68 μM for CTSL and 337.1 nM, 5.251 nM, 27.29 nM, and 172.6 nM for JAK1/2/3 and TYK2, respectively. This compound effectively prevents the activation of MAPK, NF-κB, and JAK/STAT signaling pathways, leading to significant anti-inflammatory therapeutic effects. DualCathepsinL/JAK-IN-1 is applicable in research on acute lung injury (ALI).

Isoliquiritin apioside, from Glycyrrhizae radix, inhibits MMP9, MAPK, NF-κB, reduces cancer cell invasion, angiogenesis, and fights oxidative DNA damage.

Adaptaquin is an inhibitor of the hypoxia-inducing factor prolyl hydroxylase (HIF-PH) [1] [2].

Applications Cediranib is a drug for blocking angiogenesis, study on cervical cancer molecular targeted drug and clinical application progress, value of correlative biomakers in the understanding of tumor biology. References Shao, J., et al.: Shiyong Yixue Zazhi, 31, 4143 (2015); Gerstner, E. R., et al.: Transl. Cancer Res., 5, 211 (2016)

Stability Hygroscopic Applications Dihydrochloride salt of trans-3-Hydroxy Apatinib, a metabolite of the antiangiogenic agent and selective VEGFR2 inhibitor Apatinib (A726150). References Ding, J, et al.: J. Chrom B Anal. Technol. Biomed. Life Sci., 895, 108 (2012);

EGFR/BRAFV600E-IN-4 (Compound 10f) is a dual inhibitor of EGFR and BRAFV600E, with IC50 values of 61 nM and 43 nM, respectively. It halts the cell cycle, induces apoptosis in both early and late stages, and inhibits cancer cell growth in vitro, showing broad-spectrum anticancer activity.

ZK-261991 is an orally active inhibitor of VEGFR tyrosine kinase(IC50 of 5 nM, VEGFR2).

Src Inhibitor4 (Compound 18) is a derivative of KX-01 and functions as a Src inhibitor. It effectively disrupts tumor cells, damages microtubules, and induces cell cycle arrest, apoptosis, and immunogenic cell death. After introducing phenol or aniline functional groups, Src Inhibitor4 serves as a payload conjugation site for antibody-drug conjugates, showcasing antitumor activity.

IMC-D11 (LY-3076226 antibody) is an IgG1 monoclonal antibody targeting FGFR3. It serves as the antibody component of LY3076226. For its isotype control, refer to Human IgG1 kappa, Isotype Control.

Applications (1r,4r)-4-((2-(Butylamino)-5-(5-(morpholinomethyl)pyridin-2-yl)pyrimidin-4-yl)amino)cyclohexanol inhibits steady-state phosphorylation of endogenous Mer and blocks ligand-stimulated activation of a chimeric EGFR-Mer protein. (1r,4r)-4-((2-(Butylamino)-5-(5-(morpholinomethyl)pyridin-2-yl)pyrimidin-4-yl)amino)cyclohexanol also decreases colony-forming potential in rhabdoid and NSCLC tumor cells. References Zhang, W., et. al.: J. Med. Chem., 56, 9683 (2013)

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.

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.

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. References Kim, C., et. al.: Mol. Pharmacol., 78, 142 (2010)

Applications Taurultam is a compound that inhibits cell proliferation and cell adhesion in angiogenesis. Taurultam exhibits bacteriocidal effects on Escherichia coli and is also a degradation product of Taurolidine (T009050). References Jones, D., et al.: Lett. Appl. Micro., 14, 5 (1992); Kirsch, L. & Sinn, Y.: Pharm. Dev. Tech., 2, 345 (1997); Mšhler, T., et al.: Cancer Therapy, 6, 623 (2008)

MPT0B390 is an inhibitor of HDAC and a TIMP3 inducer inhibiting tumor growth, metastasis, and angiogenesis.

Applications An antioxidant natural product which inhibits the growth of human glioma xenografts in nude mice through suppressing VEGFR expression. Used for clinical treatment for rheumatoid arthritis, was demonstrated to have antiangiogenic activity, and be inhibitory against mice tumor growth by a few recent studies. Celastrol also has been shown to have the power to kill tumor cells and can work as an anticarcinogen. Celastrol is also a leptin sensitizer with the potential to reduce weight in obesity (see W499200). References Senger, D., et al.: Science, 219, 983 (1983), Folkman, J., et al.: Nature, 1, 27 (1995), He, W., et al.: Bioorg. Med. Chem. Lett., 8, 3659 (1998), Grosios, K., et al.: Inflamm. Res., 53, 133 (2004), Yang, H., et al.: Cancer Res., 66, 4758 (2006); AAPS Newsmagazine p. 17, July 2016; Chem. and Eng. News p. 6, Aug. 8, 2016

A-935142 enhances hERG (Kv 11.1) channels, slows inactivation, promotes activation, and shortens repolarization.

Applications Optically active isomer of Thalidomide, which inhibits FGF-induced angiogenesis. Inhibits replication of human immunodeficiency virus type 1. Teratogenic sedative. References D’Amato, r.J., et al.: Proc. Natl. Acad. Sci. USA, 91, 4082 (1994), Makonkawkeyoon, S., et al.: Proc. Natl. Acad. Sci. USA, 90, 5974 (1993), Schumacher, H., et al.: J. Pharmacol. Exp. Therap., 160, 189 (1968)

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. 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);

PX-478 is a HIF-1α inhibitor with selectivity, oral activity, and blood-brain barrier permeability.

Applications Bisphenol Z-13C12 is the isotope labelled analog of Bisphenol Z. Bisphenol Z is one of the many derivatives of Bisphenol A (B519495) that can be used as HIF (hypoxia-inducible factor) inhibitors, antitumor agents, angiogenesis inhibitors, and antihypoxic agents. References Imaoka, S., Bisphenol A derivatives as HIF inhibitors. Jpn. Kokai Tokkyo Koho. JP 2011195574 A 20111006. Oct 6, 2011

AXL/Angiokinase-IN-1 (compound 11b) is an inhibitor of AXL/triple angiokinase, with an IC50 of 3.75 nM for AXL expression. This compound suppresses epithelial-mesenchymal transition (EMT) in Bxpc-3 cells and prevents metastasis in lung cancer cells. Additionally, AXL/Angiokinase-IN-1 impairs the functions of vascular and fibroblast cells and induces apoptosis in both cancer and fibroblast cells. It is characterized by low toxicity and favorable metabolic stability.

FLT3/VEGFR2-IN-1 (Compound 26) is a potent inhibitor of FLT3, VEGFR2, and HDAC, exhibiting IC50 values of 14.5 nM, 3.9 nM, and 30.8 nM against FLT3, VEGFR2, and HDAC1, respectively. It effectively inhibits the phosphorylation of STAT3 and ERK1/2, as well as the proliferation of leukemia cells. FLT3/VEGFR2-IN-1 demonstrates antitumor activity and is applicable in research on acute myeloid leukemia.

Applications Osimertinib 13CD3 is an isotope labelled compound of Osimertinib (A808075). Osimertinib is a selective EGFR inhibitor (epidermal growth factor receptor), used in the treatments of nonsmall-cell lung cancer (NSCLC). References Finlay, M.R.V., et al.: J. Med. Chem., 57, 8249 (2014);

Applications 4-​Methyl-​benzenesulfonic Acid (2E)​-​[(5R)​-​2-​Methyl-​5-​(1-​methylethenyl)​-​2-​cyclohexen-​1-​ylidene]​hydrazide-d4 is an intermediate in synthesizing (+)-Limonene-d5 (L461742). It is present in blood oranges which show inhibition of angiogenesis in human colon cancer cells. Extracted from the oils of Mentha spicata it shows antimicrobial activity. References Chidambara Murthy, K. et al.: Life Sci.,91, 429 (2012); Aggarwal, K. et al.: Flav. Frag. J., 17, 59 (2002)

Applications N-Acryloyl Osimertinib is used in the preparation of pyrimidinyl indole derivative as EGFR inhibitor for targeted therapy of cancer References Rao, Y., et al.: Faming Zhuanli Shenqing (2016), CN 105777716 A 20160720

Applications 3-Methyl-6-nitroindazole a reactant used in the preparation of Pazopanib (P210925), an oral angiogenesis inhibitor targeting VEGFR and PDGFR. References Mei, Y. et al.: Let. Org. Chem., 9, 276 (2012); Harris, P. et al.: J. Med. Chem., 51, 4632 (2008); Olaussen, K., et al.: Oncogen., 28, 4249 (2009); Sleijfer, S., et al.: J. Clin. Oncol., 27, 3126 (2009); Chan, A., et al.: Drugs, 69, 167 (2009)

EGFR/VEGFR2-IN-5 (Compound 14) is an orally active dual inhibitor of EGFR and VEGFR2, exhibiting an IC50 value of 1.15 µM for VEGFR2 and 0.28 µM for EGFRT790M. This compound demonstrates significant anticancer activity.

Applications Labelled Neratinib (N390090). An oral, irreversible dual EGFR/HER2 inhibitor for breast and non-small cell lung cancer. Antitumor agent. References Vogel, C., et al.: J. Clin. Oncol., 20, 719 (2002), Ji, H., et al.: Cancer Cell., 9, 485 (2006), Sequist, L., et al.: Oncologist, 12, 325 (2007),

JAK-IN-14 (compound 16) is a specific JAK1 inhibitor. It prevents JAK1 phosphorylation by binding to the active site of JAK in immune, inflammation and cancer.

Vorolanib (X-82) is an orally active VEGFR/PDGFR dual inhibitor.

TC-S 7009: Strong HIF-2α inhibitor (Kd 81 nM), weak for HIF-1α; disrupts dimerization & gene expression.

Ibuprofen Lysine (Neoprofen) is a non-steroidal anti-inflammatory drug.

Applications (-)-Limonene is present in blood oranges which show inhibition of angiogenesis in human colon cancer cells. Extracted from the oils of Mentha spicata it shows antimicrobial activity. Not a dangerous good if item is equal to or less than 1g/ml and there is less than 100g/ml in the package References Chidambara Murthy, K. et al.: Life Sci.,91, 429 (2012); Aggarwal, K. et al.: Flav. Frag. J., 17, 59 (2002);

Naluzotan(PRX 00023) is a novel and potent 5-HT1A agonist with IC50 and Ki values of approximately 20 nM and 5.1 nM, respectively.Naluzotan is a potent hERG K+

GN44028 is a HIF-1 inhibitor with an IC50 of 14 nM, stopping HIF-1α activity but not mRNA or protein levels, or dimerization.

Applications Deguelin exhibits potent apoptotic and antiangiogenic activities in a variety of transformed cells and cancer cells. Deguelin also exhibits potent tumor suppressive effects in xenograft tumor models for many human cancers. References Chang, D.J.. et al.: J. Med. Chem., 55, 10863 (2012);

2,4-DPD is competitive inhibitor of the oxygen-sensing enzyme HIF-α prolyl hydroxylase (HIF-PH)

E-4031 is a methanesulfonanilide class III antiarrhythmic agent that prolongs cardiac action potential duration by blocking ERG K+ channels (IC50 = 29 nM)

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.

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

Scr-IN-1 (Compound 4e) is a tyrosine kinase inhibitor demonstrating inhibitory activity against HCT-116 and MIA-PaCa-2 cells, with IC50 values of 0.16 μM and 1.16 μM, respectively. It shows selectivity towards HCT-116 cells and MIA-PaCa-2 cells, with a selectivity index (SI) greater than 625 and 86. Scr-IN-1 induces apoptosis in HCT-116 colon cancer cells without altering the proportion of necrotic cells and is a potential novel SRC kinase inhibitor for HCT-116 cells. This compound is suitable for cancer research.