Angiogenesis

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.