Peptide name : SOR-C13

Source/Organism : Synthetic

Linear/Cyclic : Linear

Chirality : L

Peptide length: 13

C-terminal modification: Linear

N-terminal modification : Free

Non-natural peptide information:

Assay type : IP

Assay time : 12 days

Activity : Effectively inhibited the growth of tumor

Cell line : SKOV-3

Cancer type : Ovarian Cancer

Other activity : Anticancer and Antitumor

Amino acid composition bar chart :

Molecular mass : 1565.814 Dalton

Aliphatic index : 0.823

Instability index : 12.7538

Hydrophobicity (GRAVY) : -0.915

Isoelectric point : 8.5973

Charge (pH 7) : 0.8492

Aromaticity : 7.692

Molar extinction coefficient (cysteine, cystine): (0, 0)

Hydrophobic/hydrophilic ratio : 0.8571

hydrophobic moment : -0.221

Missing amino acid : A,C,G,I,M,N,Q,T,W,Y

Most occurring amino acid : K

Most occurring amino acid frequency : 2

Least occurring amino acid : E

Least occurring amino acid frequency : 1

Secondary structure fraction (Helix, Turn, Sheet): (38., 30., 30.)

SMILES Notation: CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](N)CCCCN)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)O)C(C)C

1 : Xue H, et al. Inhibition of Transient Receptor Potential Vanilloid 6 channel, elevated in human ovarian cancers, reduces tumour growth in a xenograft model. J Cancer. 2018; 9:3196-3207. doi: 10.7150/jca.20639

Paper title : Inhibition of Transient Receptor Potential Vanilloid 6 channel, elevated in human ovarian cancers, reduces tumour growth in a xenograft model.

Doi : https://doi.org/10.7150/jca.20639

Abstract : Background: Transient Receptor Potential Vanilloid 6 (TRPV6), a non-voltage gated calcium channel, is implicated in malignancies and correlates with Gleason scores in prostate cancer and with poor prognosis in breast cancer. Data on the TRPV6 status of ovarian malignancies has not received significant attention. The effect of inhibiting TRPV6 activity on ovarian tumour growth has never been reported. Methods: We quantified TRPV6 mRNA and protein in biopsies of five types of ovarian cancer at different stages and grades by quantitative PCR and immunohistochemistry respectively. We verified the presence of TRPV6 in SKOV-3 cells and xenografts by Western Blotting. NOD/SCID mice bearing xenografted ovarian tumours derived from SKOV-3 were treated daily with TRPV6-antagonistic peptides (SOR-C13 and SOR-C27) at 400, 600 and 800 mg/kg delivered intraperitoneally (i.p.) over 12 days. Data from qPCR and tumour growth experiments were compared with a Student's t-test. Immunohistochemical ranking of staining were compared with Kruskall-Wallace one-way ANOVA and Dunn's Multiple Comparison post-test. Results: TRPV6 mRNA and protein are significantly elevated at all stages and grades of 5 ovarian cancer types over normal tissue. Overall qPCR log2 values (n, mean, ± SEM) for mRNA in tumour (n = 165, 5.06 ± 0.16) were greater (p < 0.05) than normal tissues (n = 26, 0.45 ± 0.41). All stages and grades included in the biopsy arrays were significantly greater than normal tissues. Immunohistochemical staining of TRPV6 was ranked >2 (faint in most cells) in 80.5% of tumours (123) while 92% of normal tissues (23) ranked ≤ 2. Daily i.p. injection with SOR-C13 (400, 600 and 800 mg/kg) over 12 days inhibits tumour growth (59%) at the highest dose compared to non-treated controls. SOR-C27 at 800 mg/kg SOR-C27 inhibited tumour growth 55% after 12 days. Results of daily and intermittent dosing (Days 1, 2, 3 and 8, 9, 10) with SOR-C13 were indistinguishable. Conclusion: TRPV6 mRNA and protein are elevated in biopsies of ovarian cancers compared to normal tissue. Inhibition of TRPV6 activity significantly reduces ovarian tumour growth providing evidence that TRPV6 is a feasible oncology target in ovarian cancers.