Kisspeptin-10 |CAS 374675-21-5|DC Chemicals

Cas No.:	374675-21-5
Chemical Name:	Kisspeptin-10
Synonyms:	L-Phenylalaninamide,L-tyrosyl-L-asparaginyl-L-tryptophyl-L-asparaginyl-L-seryl-L-phenylalanylglycyl-L-leucyl-L-arginyl-;(2S)-N-[(2S)-1-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-4-methyl-2-(methylamino)pentanamide;KISSPEPTIN 10;Kisspeptin 10 (human);Kisspeptin-13 (4-13) (human);L-Phenylalaninamide,L-tyrosyl-L-asparaginyl-L-tryptophyl-L-asparaginyl-L-seryl-L-phenylalanylg...;TYR-ASN-TRP-ASN-SER-PHE-GLY-LEU-ARG-PHE-NH2;S-Sulfo-L-cysteine sodium salt;YNWNSFGLRF-NH2
SMILES:	CC(C[C@H](NC(CNC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](N)CC1=CC=C(O)C=C1)=O)CC(N)=O)=O)CC2=CNC3=CC=CC=C23)=O)CC(N)=O)=O)CO)=O)CC4=CC=CC=C4)=O)=O)C(N[C@H](C(N[C@H](C(N)=O)CC5=CC=CC=C5)=O)CCCNC(N)=N)=O)C
Formula:	C₂₂H₃₇N₇O₃
M.Wt:	447.57428
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	Kisspeptin-10 is a potent endogenous agonist for GPR54, used as a vasoconstrictor and an angiogenesis inhibitor.
Target:	GPR54[1] Angiogenesis[1]
In Vivo:	The effects of Kisspeptin-10 (KP-10) and the GPR54 antagonist P234 are evaluated on the development of atherosclerotic lesions in 2 different strains of ApoE-/- mice (C57/B6 and BALB/c). In ApoE-/- mice (C57/B6), the (entire) surface and cross-sectional area of the root (plaque size) of aortic atherosclerotic lesions with pentraxin-3-positive area, monocyte/macrophage infiltration, and VSMC content as well as plasma total cholesterol concentration are significantly increased at 17 weeks of age compared with 13 weeks of age. By 17 weeks of age, plasma Kisspeptin-10 concentration is significantly elevated in mice infused with a high dose of Kisspeptin-10 (12.5 μg/kg per hour) compared with the vehicle control. A high dose of Kisspeptin-10 (12.5 μg/kg per hour) significantly enhances the aortic atherosclerotic lesion area and atheromatous plaque size, with significant increases in pentraxin-3-positive area and monocyte/macrophage infiltration and a significant decrease in VSMC content. There are no significant differences in body weight, food intake, systolic and diastolic BP, and plasma concentrations of either total cholesterol or glucose among the 3 groups of ApoE-/- mice at 17 weeks of age[1]. The injection of Kisspeptin-10 can slow down microvascular cutaneous blood flow in mice. The changes in cardiac metabolites in rats treated with Kisspeptin-10 is investigated using a metabonomics approarch based on GC/TOF-MS to the rats. The identification of metabolic pathways and biomarkers may contribute to understanding the mechanism by which Kisspeptin-10 treatment alters cardiac functions. Mitochondria in which energy metabolism occurs is observed through transmission electron microscope (TEM), and the perturbations in energy metabolism can be inferred from changes in mitochondrial structure. There is a clear separation between the control (N) and Kisspeptin-10 (K) groups in the plot regarding serum samples.
In Vitro:	Kisspeptin-10 (KP-10) significantly increases adhesion of THP-1 cells to HUVECs by 10-fold at 10 μM. Pretreatment with the GPR54 antagonist, P234 (20 μM), significantly inhibits Kisspeptin-10 (10 μM)-induced adhesion of THP-1 cells to HUVECs. These results indicate that Kisspeptin-10 increases the adhesion of THP-1 cells to HUVECs by GPR54. Kisspeptin-10 markedly enhances mRNA expression for TNF-α, IL-6, MCP-1, ICAM-1, VCAM-1, and E-selectin in HUVECs. Kisspeptin-10 significantly increases the protein expression of ICAM-1 and VCAM-1 in HUVECs in parallel with the increases in mRNA levels.
Cell Assay:	HUVECs, HUVEC-derived EA.hy926 cells, or HASMCs at passage 2 to 8 are seeded into 96-well plates (1×104 cells/100 μL/well) and incubated for 24 hours in DMEM or SmGM-2 containing 10% or 5% FBS, respectively. Cells are then incubated for a further 48 hours with the indicated concentrations of Kisspeptin-10 in fresh media. Ten microliters of WST-8 solution are then added to each well. After 1 hour of incubation, the quantity of formazan product is determined by reading absorbance at 450 nm using a Sunrise Remote R-micro plate reader.
Animal Administration:	Mice[1] A total of 66 of male spontaneously hyperlipidemic ApoE-/- mice in 2 strains, C57/B6 (KOR/StmSlc-Apoeshl mice) and BALB/c (KOR/StmSlc-Apoeshl mice), are used. Mice are fed a high-cholesterol diet containing 16.5% fat, 1.25% cholesterol, and 0.5% sodium cholate, starting at 13 weeks of age. Mice at 13 weeks of age are infused for 4 weeks with Kisspeptin-10 and/or P234, a GPR54 antagonist, using osmotic minipumps. The time course and dose of Kisspeptin-10 and P234 infusion are decided. Experiment 1 is performed to evaluate the dose-dependent effects of Kisspeptin-10 on atherogenesis in 17 ApoE-/- mice (C57BL/6). At 13 weeks of age, 3 mice are euthanized as preinfusion controls. The remaining 14 are divided into 3 groups of 5, 4, and 5 and then infused with saline (vehicle) or Kisspeptin-10 at doses of 5 and 12.5 μg/kg per hour, respectively. Experiment 2 is performed to evaluate the suppressive effects of P234 on Kisspeptin-10-induced atherogenesis in 38 ApoE-/- mice (BALB/c). At 13 weeks of age, 7 mice are euthanized as a control before infusion. The remaining 31 are divided into 3 groups of 10, 10, and 11 and are then infused with saline, Kisspeptin-10 (12.5 μg/kg per hour) or Kisspeptin-10 (12.5 μg/kg per hour)+P234 (50 μg/kg per hour), respectively. Experiment 3 is performed to evaluate the preventive effects of P234 on endogenous Kisspeptin-10-induced atherogenesis (the natural course of atherogenesis) in 10 ApoE-/- mice (BALB/c). From 13 to 17 weeks of age, 5 and 5 mice are infused with saline and P234 (50 μg/kg per hour), respectively[1]. Rats[2] Twenty eight-week-old male Sprague-Dawley rats weighing 200±20 g are used. They are maintained at constant temperature (23±2°C) and humidity (45±15%), with controlled lighting (light 12 h-dark 12 h), and are fed at a standard diet, with free access to tap water. They are adapted to the environment for two weeks to overcome the stress of transportation before the animal experiments began. Then, all of the rats are divided into two groups randomly. Each rat in Kisspeptin-10 group receives subcutaneous injection with 200 μL Kisspeptin-10 (40 nmol/200μL) every day, each rat of the control group receives subcutaneous injection with 200 μL saline every day, both of the two groups are treated for 7 days continuously. Rats are anesthetized with urethane (1.5 g/kg, i.p.). Under general anesthesia, blood samples are collected and rats are euthanized. All efforts are made to minimize the discomfort and stress of animals. Then all the samples are analyzed. Seven days later, the 20 rats are decapitated after exposure to anesthesia. Cardiac tissue and serum samples are collected and stored at -80°C until being used for total RNA and protein extraction as well as metabonomics analysis. The rest of the heart tissue is fixed with 4% paraformaldehyde and 2.5% glutaraldehyde for 24 h at 4°C for further morphological research.
References:	[1]. Sato K, et al. Potent Vasoconstrictor Kisspeptin-10 Induces Atherosclerotic Plaque Progression and Instability: Reversal by its Receptor GPR54 Antagonist. J Am Heart Assoc. [2]. Zhang Y, et al. The effects of kisspeptin-10 on serum metabolism and myocardium in rats. PLoS One.

MSDS

Cat. No.	Product name	Field of application
DC12145	DLinDMA	DLinDMA is a key lipid component of stable nucleic acid lipid particles as a benchmark.
DC40169	DMG-PEG2000	DMG-PEG 2000 is used for the preparation of liposome for siRNA delivery with improved transfection efficiency in vitro. DMG-PEG 2000 is also used for the lipid nanoparticle for an oral plasmid DNA delivery approach in vivo through a facile surface modific
DC45611	DMPC	1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) is a synthetic phospholipid used in liposomes. 1,2-Dimyristoyl-sn-glycero-3-phosphocholine is used for the study of lipid monolayers and bilayers.
DC70000	Lysyllysyllysine	Lysyllysyllysine is a cationic moietie that may be used in the construction of gene delivery vectors and DNA nanoparticles.
DC33580	DODMA	DODMA, also known as MBN 305A is a a cationic lipid containing the unsaturated long-chain (18:1) oleic acid inserted at both the sn-1 and sn-2 positions. It has been used in the composition of lipospomes formulated as stable nucleic acid lipid particles that can encapsulate siRNA or other small molecules to be used for drug delivery
DC33635	DODAP	DODAP, also known as 1,2-Dioleoyl-3-dimethylammonium-propane, is a cationic lipid. It has been used as a component in liposomes that can be used to encapsulate siRNA, immunostimulatory oligodeoxynucleotides, antisense oligonucleotides, or chemotherapeutic agents for in vitro and in vivo delivery.
DC59010	C14-4 (C14-494,Lipid B-4,Lipid B4)	C14-4 (C14-494,Lipid B-4,Lipid B4) is a novel ionizable lipid with the highest T-cell transfection efficiency and low cytotoxicity.The C14-4 ionizable lipid has been explored for CAR-T therapy.To screen the excellent formulations for mRNA delivery, a lipid library of 24 ionizable lipids was constructed to make iLNPs, which were used to deliver luciferase mRNA into Jurkat cells.[115] The optimal iLNPs formulation was C14-4 iLNPs (C14-4 ionizable lipid, DOPE, chol, and PEG at a molar ratio of 35%, 16%, 46.5%, and 2.5%) (Figure 6c). The optimal dose of luciferase mRNA for C14-4 iLNPs was 30 ng. Compared with electroporated CAR T cells, the CAR T cells engineered via C14-4 iLNPs showed potent cancer-killing activity when they were cocultured with Nalm-6 acute lymphoblastic leukemia cells. To obtain a safer and more effective CAR mRNA delivery vehicle, the orthogonal design provided 256 potential formulations, and 16 representative iLNPs formulations were evaluated.Through evaluating the safety, delivery efficiency, and transfection efficiency of 16 iLNPs, the formulation B10 (C14-4 ionizable lipid, DOPE, chol, PEG at a molar ratio of 40%, 30%, 25%, and 2.5%) was screened out as the optimal performing formulation. The luciferase expression based on B10 formulation was increased threefold than the initial formulation. Reducing the accumulation and clearance of iLNPs in the liver can increase the expression of CAR mRNA in T cells, further improving the therapeutic effect of CAR-T. Studies have shown that cholesterol analogs can alter the mechanisms of intracellular circulation and enhance the delivery of mRNA, which may be related to the reduced recognition of iLNPs by the Niemann Pick C1 (NPC1) enzyme.The addition of a hydroxyl group to various locations in the cholesterol molecule can alter the binding kinetics between the modified cholesterol and NPC1, and reduced NPC1 recognition of cholesterol. The results showed that replacement of 25% and 50% 7 α-hydroxycholesterol for cholesterol in iLNPs improved mRNA delivery to primary human T cells in vitro by 1.8-fold and twofold, respectively.C14-4 is one of the ionizable lipids to efficiently deliver mRNA to Jurkat cells or primary human T cells. It will effectively promote the development of mRNA delivery by iLNPs for CAR-T therapy.
DC33636	DOTAP	DOTAP, also known as 1,2-Dioleoyl-3-trimethylammoniumpropane, is a cationic liposome-forming compound used for transfection of DNA, RNA, and other negatively charged molecules into eukaryotic cells. It has been used in gene delivery vectors for gene ther
DC58047	DSPE-PEG 2000	PEG2000-DSPE is used for creating micelles that are able to carry drugs with low solubility.
DC31000	LP-01	LP-01 is an ionizable cationic amino lipid (pKa = ~6.1). It has been used in the generation of lipid nanoparticles (LNPs). LNPs containing LP-01 and encapsulating both Cas9 mRNA and modified single-guide RNA (sgRNA) for the transport protein transthyretin (Ttr) induce gene editing in liver cells in mice in a dose-dependent manner resulting in reduced serum Ttr levels for at least 12 months.