| Identification | Back Directory | [Name]
L-Cysteinamide, N-acetyl-L-cysteinyl-L-arginylglycyl-L-α-aspartyl-L-lysylglycyl-L-prolyl-L-α-aspartyl-, cyclic (1→9)-disulfide | [CAS]
2580154-02-3 | [Synonyms]
Certepetide
L-Cysteinamide, N-acetyl-L-cysteinyl-L-arginylglycyl-L-α-aspartyl-L-lysylglycyl-L-prolyl-L-α-aspartyl-, cyclic (1→9)-disulfide | [Molecular Formula]
C37H60N14O14S2 | [MOL File]
2580154-02-3.mol | [Molecular Weight]
989.09 |
| Hazard Information | Back Directory | [Uses]
Certepetide (CEND-1) is a bifunctional cyclic peptide (a.k.a. iRGD). Certepetide is a tumor-penetrating enhancer via RGD motif interaction with alphav-integrins and via activating NRP-1, and transforms the solid tumor microenvironment into a temporary agent conduit. Certepetide accumulates in tumors, and is used in the research of pancreatic cancer and other solid tumors[1][2][3]. | [in vivo]
CEND-1 (iRGD) can modulate the solid tumour microenvironment, enhancing the delivery and therapeutic index of co-administered anti-cancer agents[4].
CEND-1 enhances the penetration of anticancer therapeutics specifically into tumours, but not into normal tissues, it also holds the potential for dose reductions, which can attenuate side effects[4].
CEND-1 (intravenously injected) increases the levels of co-administered Evans blue approximately threefold[5].
Table 1. Derived mean pharmacokinetic parameters for CEND-1 in mouse, rat, dog and monkey plasma after a single intravenous infusion of CEND-1 (±SD) [5].
| | Number of Animals (Sex) | CEND-1 Dose (mg/kg) | t1/2 (h) | C0 (ng/mL) | V (mL/kg) | Cl_obs (mL/hr/kg) | AUC0-inf (h*ng/mL) | | Mouse * | | | | | | | | 3 (M) | 1.5 | 0.306 | 10,343 | 449 | 1016 | 1476 | | 3 (M) | 13.5 | 0.547 | 68,358 | 1007 | 1277 | 10,569 | | Rat* | | | | | | | | 6 (M) | 75 | 0.341 | 469,000 | 171 | 348 | 215,476 | | 6 (F) | 75 | 0.391 | 436,333 | 254 | 451 | 166,331 | | Dog* | | | | | | | | 3 (M) | 1 | 0.665 (0.0448) | 6010 (1985) | 241 (27) | 253 (40.1) | 4030 (686) | | 3 (F) | 5 | 0.648 (0.0486) | 25,133 (3635) | 230 (14.6) | 247 (32.9) | 20,443 (2530) | | Monkey* | | | | | | | | 3 (M) | 5 | 0.888 (0.0963) | 55,082 (19,905) | 204 (14.1) | 179 (23.4) | 28,230 (3865) | | 3 (M) | 50 | 0.956 (0.0869) | 602,161 (211,386) | 162 (32.1) | 178 (51.9) | 421,119 (171,418) |
Note:* Because of volume limitations in the mice and rats, each animal was used for one time point sampling, limiting the statistical analysis of the data. M, male; F, female.
| [References]
[1] International Nonproprietary Names for Pharmaceutical Substances (INN). WHO Drug Information, Vol. 36, No. 2, 2022
[2] Ruoslahti Erkki, et al. Methods for treating pancreatic cancer and other solid tumors. WO2021226148.
[3] Andrew Peter Dean, et al. Updated single institution outcome data from the first-in-human CEND-1 trial in metastatic pancreatic cancer. Journal of Clinical Oncology 2021 39:15_suppl, e16274-e16274
[4] Harri A J?rvel?inen, et al. Assessment of the Pharmacokinetics, Disposition, and Duration of Action of the Tumour-Targeting Peptide CEND-1. Int J Mol Sci. 2023 Mar 16;24(6):5700. DOI:10.3390/ijms24065700
[5] Schmithals, C, et al. Improving Drug Penetrability with iRGD Leverages the Therapeutic Response to Sorafenib and Doxorubicin in Hepatocellular Carcinoma. Cancer Res. 2015 Aug 1;75(15):3147-54. DOI:10.1158/0008-5472.CAN-15-0395 |
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