TCMCB07 [a cyclic substituted melanocortin antagonist with the structure Ac- Nle- cyclo[Asp- Pro- DNal(2’)-Arg- Trp- Lys]- DVal- DPro- NH2] was manufactured by CPC Scientific Inc. under cGMP conditions. Active pharmaceutical ingredient was dissolved in milliQ water at 10 mg ml−1, sterile filtered [..]”
Abstract
The melanocortin‐4 receptor (MC4R) antagonistic peptide TCMCB07 was developed for the treatment of cachexia. The objectives of this study were to examine pharmacokinetics and safety of TCMCB07 administered subcutaneously to healthy dogs. Dogs were treated with high‐ (2.25 mg kg−1) (n = 5) and low‐dose TCMCB07 (0.75 mg kg−1) (n = 5) once daily for 28 days with a 14‐day washout period between groups. Histamine levels, complete blood count, chemistry panel, blood pressure, 24‐hour Holter recording, and pharmacokinetic parameters were monitored in the high‐dose group. Physical examination changes were limited to weight gain and darkening of the coat color. There was no elevation of plasma histamine within 24 hours of injection but there was a significant elevation of plasma histamine across time. An approximately doubled eosinophil count and an approximately 25% increase, and then 25% decrease back to pre‐treatment plasma phosphorous were also found, although both remained within the reference interval. Serial blood pressure and 24‐hour Holter monitors revealed no clinically relevant changes. A difference was found in the AUC between dosing groups and a significant effect of dose, time, and interaction was noted for Vd. Low‐dose TCMCB07 had a Cmax of 2.1 ug ml−1 at day 28, compared to high‐dose TCMCB07 which had a Cmax 3.6 ug ml−1 at day 28. Once‐daily subcutaneous administration of TCMCB07 was well‐tolerated for up to 28 days in dogs when administered at doses one and three times (0.75 mg kg−1 and 2.25 mg kg−1) the predicted therapeutic dose and pharmacokinetic parameters are described.
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CPC Scientific Inc., a leading global peptide CRDMO (Contract Research, Development, and Manufacturing Organization) has invested in a new peptide API (Active Pharmaceutical Ingredient) manufacturing site, bringing many new jobs to Rocklin, California. The 41,000 sq ft facility located at 3880 Atherton Rd, Rocklin, CA 95765 will be utilized to manufacture clinical to commercial grade peptide products for increased manufacturing capacity and will diversify CPC Scientific’s supply chain.
CPC Scientific is entering an exciting period of growth and innovation for peptide and oligonucleotide therapeutic development and manufacturing, and we will continue to provide therapeutic APIs to pharmaceutical and biotech companies around the world. We are very pleased to partner with the City of Rocklin, California to bring manufacturing and Life-Science jobs to local American workers,” said Shawn Lee, PhD, CEO.
Ikeda, Z., Kakegawa, K., Kikuchi, F., Itono, S., Oki, H., Yashiro, H., Hiyoshi, H., Tsuchimori, K., Hamagami, K., Watanabe, M. and Sasaki, M. Journal of Medicinal Chemistry 65, no. 12 (2022): 8456-8477.
- Research, Takeda Pharmaceutical Company Limited, 26-1, Muraokahigashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan
Subsequently, 5FAM–Abu–Gly–Asp–Asp–Asp–Lys–Ile–Val–Gly–Gly–Lys(CPQ2)–Lys–Lys–NH2 (purity: 97.2%, CPC Scientific, Inc.) was diluted with an assay buffer to prepare a 2.1 μM substrate solution.
The transferred energy from a fluorescent donor is converted into molecular vibrations if the acceptor is a non-fluorescent dye (quencher). When the FRET is terminated (by separating donor and acceptor), an increase of donor fluorescence can be detected. The design and synthesis work at CPC for FRET and TR-FRET peptide substrates include modification of sequences, selection of donor/quencher pairs, improvement of FRET substrate solubility and quenching efficiency.
Genomics research shows that more than a million proteins are encoded by approximately 30,000 human genes. Proteomics, the study of proteins encoded by the genome, includes identifying post-translational modifications, structural analyses, protein localization studies, and protein quantitation. Mass spectroscopybased techniques have evolved as a powerful tool in proteomics. Stable isotope-labeled peptides (SIL peptides) are chemically and physically indistinguishable from their endogenous counterparts concerning retention time, ionization efficiency, and fragmentation pathways.
Peptides play a vital role in the pharmaceutical industry and drug therapeutic development; however, their in vivo applications are sometimes limited due to fast degradation by proteases, poor solubility, antigenic responses, and glomerular filtration in the kidney. The covalent attachment of polyethylene glycol (PEG) chains to peptides is one approach that can reduce immunogenicity, improve solubility, and reduce renal clearance.
Hydrocarbon-stapled peptides are locked into their bioactive alpha-helical conformation through the site-specific introduction of a chemical brace, an all-hydrocarbon staple. The idea of peptide stapling was introduced to overcome the limitations of two broad classes of therapeutic agents (small molecules and protein biologics) in targeting intracellular protein-protein interactions. Small molecules only work on proteins with a specific surface feature, and most protein biologics do not penetrate cells. Because stapled peptides are locked into a stabilized α-helical structure (the most common element of protein secondary structures), they can easily penetrate cells.
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Mogford, Jon E., George E. Davis, Steven H. Platts, and Gerald A. Meininger. Circulation research 79, no. 4 (1996): 821-826.
Locmi-AKH-I, cycloAKH (cyclo[LNFTPNWG]
CPC Scientific is pleased to announce and welcome David A. Godkin as VP of Business Operations! David will be responsible for the growth and development of our HR department and facilities management division. He brings 20+ years of experience in human resources and facility operations from the peptide industry. We are confident David will have […]
Bekdemir, Ahmet, Eden EL Tanner, Jesse Kirkpatrick, Ava P. Soleimany, Samir Mitragotri, and Sangeeta N. Bhatia Advanced Healthcare Materials (2022): 2102685.
Peptides [TDN-qFAM, C-(PEG)2-K(CPQ2)-GGGSRPfGG-5FAM] were obtained from Tufts University Peptide Core Facility or CPC Scientific, Inc (USA)
