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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Shurtleff, V.W., Layton, M.E., Parish, C.A., Perkins, J.J., Schreier, J.D., Wang, Y., Adam, G.C., Alvarez, N., Bahmanjah, S., Bahnck-Teets, C.M. and Boyce, C.W. Journal of Medicinal Chemistry 67, no. 5 (2024): 3935-3958.
- Center for Discovery and Innovation, Hackensack Meridian Health. 111 Ideation Way. Nutley, New Jersey 07110, United States.
- Merck & Co., Inc., Rahway, New Jersey 07065, United States.
The enzymatic activity of recombinantly expressed 3CLPro enzymes from different coronaviruses was measured using the following synthetic quenched FRET peptide: CP488-ESATLQSGLRKAK- (CPQ2)-NH2 (CPC Scientific, San Jose, CA.
Goh, Joleen Pei Zhen. Nanyang Technological University (2023)
9 generic fluorogenic substrates (CPC Scientific) (Figure S4) were added to the final concentration of 20 μM. Fluorescence was measured at Excitation/Emission=330/390 nm on BioTek Synergy H1 microplate reader and proteolytic activity was calculated as a change in relative fluorescence units per sec using the slope of the linear range for this signal.
Design-rules for stapled peptides with in vivo activity and their application to Mdm2/X antagonists.
Chandramohan, A., Josien, H., Yuen, T.Y., Duggal, R., Spiegelberg, D., Yan, L., Juang, Y.C.A., Ge, L., Aronica, P.G., Kaan, H.Y.K. and Lim, Y.H. Nature Communications 15, no. 1 (2024): 489.
- Merck & Co., Inc., Kenilworth, NJ 07033, USA.
- Merck & Co., Inc., Boston, MA 02115, USA
- Merck & Co., Inc., West Point, PA 19486, USA
- Genentech, South San Francisco, CA 94080, USA
We thank Evans (Chen) Ge, Mike (Dixin) Xue, and Simon (Junhua) Li at Chinese Peptide Company (CPC) for peptide synthesis support.
Hao, Liangliang, Renee T. Zhao, Nicole L. Welch, Edward Kah Wei Tan, Qian Zhong, Nour Saida Harzallah, Chayanon Ngambenjawong et al. Nature Nanotechnology (2023): 1-10.
All peptides and oligonucleotides were synthesized and HPLC purified by CPC Scientific and Integrated DNA Technologies (IDT), respectively. Peptide–oligonucleotide conjugates were generated by copper-free click chemistry.
Kikuchi, F., Ikeda, Z., Kakegawa, K., Nishikawa, Y., Sasaki, S., Fukuda, K., Takami, K., Banno, Y., Nishikawa, H., Taya, N. and Nakahata, T. Bioorganic & Medicinal Chemistry 93 (2023): 117462.
- Research, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan
- Pharmaceutical Sciences, Takeda Pharmaceutical Company Ltd., 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan
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 5.4 μM substrate solution.
Senotherapeutic peptide treatment reduces biological age and senescence burden in human skin models.
Zonari, A.; Brace, L. E.; Al-Katib, K.; Porto, W. F.; Foyt, D.; Guiang, M.; Cruz, E. A. O.; Marshall, B.; Gentz, M.; Guimaraes, G. R.; Franco, O. L.; Oliveira, C. R.; Boroni, M.; Carvalho, J. L., NPJ Aging 2023, 9 (1), 10.
The top hit peptides selected (Pep 14, 144, 156, 195, and 393) from the screening and the fluorescence labeled peptide (5FAM-PEG2-Pep 14) were purchased from CPC Scientific Inc. (USA), which synthesized the peptide by solid phase (Fmoc) on a Rink amide resin, with >95% purity, in the form of acetate salt.
Synthetic oligonucleotides constitute an important class of therapeutics developed to treat a variety of indications. Two main synthetic approaches exist for the conjugation of a peptide to an oligonucleotide: parallel and linear. The primary benefit of the linear approach is the one-pot solid-phase assembly and compatibility with machine automation. However, in cases where poor compatibility of peptide and oligo chemistries exist or long peptide and oligo fragments are required, preparing both components separately and linking both compounds together may offer the simplest solution.
Solid-phase peptide synthesis (SPPS) approaches require that the side chains of certain amino acids be protected from undesired reactivity during synthesis. The installation and removal of these protection groups results in a lower atom economy in the production process. Removal of the protection groups often requires large volumes of trifluoroacetic acid (TFA) or other strong acids which can result in lower yields and pose a significant risk to the environment.
Schiemer, J., Maxwell, A., Horst, R., Liu, S., Uccello, D.P., Borzilleri, K., Rajamohan, N., Brown, M.F. and Calabrese, M.F. Nature Communications 14, no. 1 (2023): 1189.
- Discovery Sciences, Pfizer Worldwide Research and Development, Groton, CT, USA
After 3 h the resin was washed with binding buffer until no protein was detected, followed by elution with 0.2 mg ml−1 FLAG peptide DYKDDDDK (CPC Scientific Peptide company)
