765930-98-1Relevant academic research and scientific papers
Constraining the Side Chain of C-Terminal Amino Acids in Apelin-13 Greatly Increases Affinity, Modulates Signaling, and Improves the Pharmacokinetic Profile
Tran, Kien,Van Den Hauwe, Robin,Sainsily, Xavier,Couvineau, Pierre,C?té, Jér?me,Simard, Louise,Echevarria, Marco,Murza, Alexandre,Serre, Alexandra,Théroux, Léa,Saibi, Sabrina,Haroune, Lounès,Longpré, Jean-Michel,Lesur, Olivier,Auger-Messier, Mannix,Spino, Claude,Bouvier, Michel,Sarret, Philippe,Ballet, Steven,Marsault, éric
supporting information, p. 5345 - 5364 (2021/02/16)
Side-chain-constrained amino acids are useful tools to modulate the biological properties of peptides. In this study, we applied side-chain constraints to apelin-13 (Ape13) by substituting the Pro12 and Phe13 positions, affecting the binding affinity and signaling profile on the apelin receptor (APJ). The residues 1Nal, Trp, and Aia were found to be beneficial substitutions for Pro12, and the resulting analogues displayed high affinity for APJ (Ki 0.08-0.18 nM vs Ape13 Ki 0.7 nM). Besides, constrained (d-Tic) or α,α-disubstituted residues (Dbzg; d-α-Me-Tyr(OBn)) were favorable for the Phe13 position. Compounds 47 (Pro12-Phe13 replaced by Aia-Phe, Ki 0.08 nM) and 53 (Pro12-Phe13 replaced by 1Nal-Dbzg, Ki 0.08 nM) are the most potent Ape13 analogues activating the Gα12 pathways (53, EC50 Gα12 2.8 nM vs Ape13, EC50 43 nM) known to date, displaying high affinity, resistance to ACE2 cleavage as well as improved pharmacokinetics in vitro (t1/2 5.8-7.3 h in rat plasma) and in vivo.
Compounds for treating tumors
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Page 52; 53, (2008/06/13)
The invention provides compounds of formula (I): wherein E, A, B′, R6, R7, R8, and R9 are defined in the specification which compounds exhibit anticancer activity and are useful for treating cancer.
Synthesis and biological activity of analogues of the antimicrotubule agent N,β,β-trimethyl-L-phenylalanyl-N1-[(1S,2E)-carboxy-1- isopropylbut-2-enyl]-N13-dimethyl-L-valinamide (HTI-286)
Zask, Arie,Birnberg, Gary,Cheung, Katherine,Kaplan, Joshua,Niu, Chuan,Norton, Emily,Suayan, Ronald,Yamashita, Ayako,Cole, Derek,Tang, Zhilian,Krishnamurthy, Girija,Williamson, Robert,Khafizova, Gulnaz,Musto, Sylvia,Hernandez, Richard,Annable, Tami,Yang, Xiaoran,Discafani, Carolyn,Beyer, Carl,Greenberger, Lee M.,Loganzo, Frank,Ayral-Kaloustian, Semiramis
, p. 4774 - 4786 (2007/10/03)
Hemiasterlin (1), a tripeptide isolated from marine sponges, induces microtubule depolymerization and mitotic arrest in cells. HTI-286 (2), an analogue from an initial study of the hemiasterlins, is presently in clinical trials. In addition to its potent
