KS-133
Based on 1 Customer Validation
KS-133 is a bicyclic peptide with VIPR2 antagonistic activity that can cross the blood-brain barrier. KS-133 selectively blocks VIPR2-mediated Gq/Ca, Gs/cAMP, cAMP/PKA/ERK and PI3K/AKT/GSK3β signaling pathways. KS-133 inhibits VIPR2 agonist-induced CREB phosphorylation in the prefrontal cortex of mice. KS-133 shifts the polarization direction of macrophages toward M1. KS-133 attenuates cancer cell proliferation and reduces the cell cycle distribution level at the S-M phase. KS-133 exerts antitumor effects in a mouse model of colorectal cancer. KS-133 reverses cognitive decline in mouse models of psychiatric disorders. KS-133 can be used for research related to schizophrenia, colorectal cancer and breast cancer.
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- Purity: 98.75%
- CAS No.: 2724212-01-3
- 화학식: C75H111N15O17S2
- 분자량:1558.90
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보관:
Sealed storage, away from moisture.
Powder -80°C, 2 years , -20°C, 1 year* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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용액&용해도
- 순도&문서
- References
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Help & FAQs
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Biological Activity
KS-133 (30 min) potently and selectively antagonizes human VIPR2-mediated calcium influx signaling and cAMP production, with IC50 values of 24.8 nM and 500 nM, respectively[1].
KS-133 (1-10 μM; 3 days) polarizes RAW264.7 mouse macrophage-like cells toward the M1 phenotype by upregulating the expression of iNOS and CXCL10, and downregulating the mRNA expression of Mrc-1[2].
KS-133 (100 nM; 3 days) significantly inhibits vasoactive intestinal peptide (VIP)-induced proliferation of MCF-7 cells stably overexpressing EGFP, and slows down or arrests division in a subset of cells[4].
KS-133 (100 nM; 24-48 h) blocks VIP-induced progression of MCF-7 cells to the S and G2-M phases and inhibits the G1/S phase transition[4].
KS-133 (pre-incubated for 3 h, followed by co-treatment with VIP for 10 or 3 h) inhibits VIP-induced activation of the ERK, AKT and GSK3β pathways, and reduces VIP-induced cyclin D1 levels in MCF-7 cells[4].
KS-133 (pre-incubated for 3 h, followed by co-treatment with VIP for 10 min) reduces VIP-induced PI3K activity and cAMP production by approximately 60% and 40%, respectively, in MCF-7 cells stably expressing VIPR2-EGFP, without altering the expression of PI3Kγ[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:RAW264.7 murine macrophage-like cells
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Concentration:1, 3, 10 μM
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Incubation Time:3 days
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Result:Significantly enhanced mRNA expression of the M1-type macrophage markers iNOS and CXCL10.
Significantly decreased mRNA expression of the M2-type macrophage marker Mrc-1.
Showed no significant effects on TNFα, IL-1Rn, or CCL22 mRNA expression.
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Cell Line:MCF-7 cells stably overexpressing EGFP
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Concentration:100 nM
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Incubation Time:3 days
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Result:Significantly decreased the proliferation of MCF-7 cells compared with untreated cells.
Slowed or halted cell division in some cells over 3 days of observation.
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Cell Line:MCF-7 cells
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Concentration:100 nM
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Incubation Time:24 h; 48 h
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Result:Attenuated VIP-induced increases in the percentage of cells in both S and G2-M phases, reducing the proportion of cells in the combined S-M phase from ~30% to ~12%.
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Cell Line:MCF-7 cells
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Concentration:100 nM
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Incubation Time:3 h pre-incubation, then 10 min co-treatment with VIP; 3 h pre-incubation, then 3 h co-treatment with VIP
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Result:Decreased VIP-induced phosphorylation of ERK1/2 (Thr202/Tyr204) by approximately 50%.
Decreased VIP-induced phosphorylation of AKT (Thr308) by approximately 70%.
Decreased VIP-induced phosphorylation of GSK3β (Ser9) by approximately 40%.
Decreased VIP-induced cyclin D1 protein levels by approximately 65%.
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Cell Line:MCF-7 cells stably expressing VIPR2-EGFP
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Concentration:100 nM
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Incubation Time:3 h pre-incubation, then 10 min co-treatment with VIP
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Result:Attenuated VIP-induced increases in cAMP levels to approximately 60% of that in KS-133-untreated cells.
Both KS-133 (30 μg per mouse; s.c.; once daily for 3 weeks) and KS-133 nanoparticles (NPs) (30 μg per mouse; s.c.; once daily or once every 3 days for 3 weeks) exhibit potent antitumor activity; KS-133 NPs reduce tumor volume to 38% of that in the control group, while unformulated KS-133 combined with anti-PD-1 antibody reduces tumor volume to 32% of that in the control group[2].
KS-133 (3 mg/kg, s.c., once daily for 14 consecutive days) significantly ameliorates cognitive dysfunction in a mouse model of schizophrenia, as indicated by an increased discrimination index, and reaches concentrations in brain regions sufficient to exert VIPR2 antagonist activity[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:ICR (CD1) (male, postnatal day 12, 7-10 g, schizophrenia-related model via VIPR2 agonist Ro 25-1553 treatment); C57BL/6J (male, 8 weeks of age, 20-30 g, schizophrenia-related model via VIPR2 agonist BAY 55-9837 treatment);ICR (CD1) (male, treated from postnatal day 1 to 14, tested at 2-3 months of age, schizophrenia-related model via daily VIPR2 agonist Ro 25-1553 treatment from P1 to P14)[1]
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Dosage:1 nmol/g; 20 nmol/mouse;1 nmol/g
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Administration:s.c.; single simultaneous injection with Ro 25-1553; i.n.; single simultaneous injection with BAY 55-9837;s.c.; once daily; postnatal day 1 to 14, simultaneous with daily Ro 25-1553 injections
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Result:Significantly reduced pCREB/CREB ratio and pCREB/β-actin ratio compared to the Ro 25-1553-only group.
Significantly reduced pCREB/CREB ratio and pCREB/β-actin ratio compared to the BAY 55-9837-only group.
Significantly increased the discrimination index in the novel object recognition test compared to the Ro 25-1553-only group, matching control levels.
Prevented Ro 25-1553-induced reductions in prefrontal cortex pyramidal neuron soma size, total apical and basal dendrite branch number, and total apical and basal dendrite length.
Reversed Ro 25-1553-induced reduction in dendritic complexity (decreased number of dendrite intersections at increasing distances from the soma) for both apical and basal dendrites via Sholl analysis.
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Animal Model:BALB/cCrSlc (female, 6 weeks old, subcutaneous allograft tumor model)[2]
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Dosage:30 μg/mouse (daily single agent); 30 μg/mouse (once every 3 days single agent); 30 μg/mouse (daily, combined with anti-PD-1 antibody)
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Administration:s.c.; daily; 3 weeks; s.c.; once every 3 days; 3 weeks
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Result:Reduced tumor volume to 66% of control group at day 21 (daily non-formulated KS-133).
Reduced tumor volume to 60% of control group at day 21 (daily KS-133 NPs).
Reduced tumor volume to 38% of control group at day 21 (KS-133 NPs administered once every 3 days).
Reduced tumor volume to 32% of control group at day 21 (daily non-formulated KS-133 combined with anti-PD-1 antibody).
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Animal Model:early postnatal treatment with VIPR2 agonist Ro 25−1553 to induce schizophrenia model[3]
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Dosage:3 mg/kg
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Administration:s.c.; once daily; 14 days
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Result:Increased discrimination index significantly compared to schizophrenia model vehicle control group.
Reached peak concentrations in brain regions at 1-2 hours post-administration: 0.054 μmol/kg in cerebral cortex, 0.058 μmol/kg in hypothalamus, 0.062 μmol/kg in hippocampus, 0.044 μmol/kg in striatum, and 0.103 μmol/kg in cerebellum.
Chemical Information
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CAS No. 2724212-01-3
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Appearance Solid
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분자량 1558.90
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화학식 C75H111N15O17S2
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Color White to off-white
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Sequence
Ac-Cys-Pro-Pro-Tyr-Leu-Pro-cyclo(Lys-Tyr-Leu-Cys-Asp)-Leu-Ile-NH2 (disulfide bridge:Cys1-Cys10)
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Sealed storage, away from moisture
Powder -80°C 2 years -20°C 1 year * In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
용액&용해도
DMSO : 100 mg/mL (64.15 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (1.60 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
순도&문서
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Data Sheet (297 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
[1]. Sakamoto K, et al. Generation of KS-133 as a Novel Bicyclic Peptide with a Potent and Selective VIPR2 Antagonist Activity that Counteracts Cognitive Decline in a Mouse Model of Psychiatric Disorders. Front Pharmacol. 2021;12:751587. Published 2021 Nov 4. [Content Brief]
[2]. Sakamoto K, et al. The VIPR2-selective antagonist KS-133 changes macrophage polarization and exerts potent anti-tumor effects as a single agent and in combination with an anti-PD-1 antibody. PLoS One. 2023;18(7):e0286651. Published 2023 Jul 5. [Content Brief]
[3]. Sakamoto K, et al. Cyclic Peptides KS-133 and KS-487 Multifunctionalized Nanoparticles Enable Efficient Brain Targeting for Treating Schizophrenia. JACS Au. 2024;4(8):2811-2817. Published 2024 Jun 20. [Content Brief]
[4]. Asano S, et al. Blockade of vasoactive intestinal peptide receptor 2 (VIPR2) signaling suppresses cyclin D1-dependent cell-cycle progression in MCF-7 cells. J Pharmacol Sci. 2024;154(3):139-147. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 0.6415 mL | 3.2074 mL | 6.4148 mL | 16.0369 mL |
| 5 mM | 0.1283 mL | 0.6415 mL | 1.2830 mL | 3.2074 mL | |
| 10 mM | 0.0641 mL | 0.3207 mL | 0.6415 mL | 1.6037 mL | |
| 15 mM | 0.0428 mL | 0.2138 mL | 0.4277 mL | 1.0691 mL | |
| 20 mM | 0.0321 mL | 0.1604 mL | 0.3207 mL | 0.8018 mL | |
| 25 mM | 0.0257 mL | 0.1283 mL | 0.2566 mL | 0.6415 mL | |
| 30 mM | 0.0214 mL | 0.1069 mL | 0.2138 mL | 0.5346 mL | |
| 40 mM | 0.0160 mL | 0.0802 mL | 0.1604 mL | 0.4009 mL | |
| 50 mM | 0.0128 mL | 0.0641 mL | 0.1283 mL | 0.3207 mL | |
| 60 mM | 0.0107 mL | 0.0535 mL | 0.1069 mL | 0.2673 mL |
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