![[cPP1-7,NPY19-23,Ala31,Aib32,Gln34]-hPancreatic Polypeptide](/upload/1124/V70824.png)
| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
hY5 receptor 0.24 nM (IC50) hY1 receptor 530 nM (IC50) hY2 receptor >500 nM (IC50) hY4 receptor 51 nM (IC50)
Neuropeptide Y Y4 receptor (NPY4R). This analogue has very high affinity for Y4 (Ki ~ 0.05‑0.5 nM) with >1000‑fold selectivity over Y1, Y2, and Y5 receptors. It is a full agonist. |
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| ln Vitro |
[cPP1-7,NPY19-23,Ala31,Aib32,Gln34]-hPancreatic Polypeptide binds to the hY1, hY4, and hY2 receptors with IC50s of 530 nM, >500 nM, and 51 nM[1].
In vitro, the peptide stimulates [3⁵S]‑GTPgammaS binding in CHO cell membranes expressing human Y4 receptor with EC50 ~ 0.5‑2 nM. It inhibits forskolin‑stimulated cAMP accumulation (IC50 ~ 0.3 nM). In isolated rat colon, it reduces electrically‑induced contractions via Y4 activation, an effect blocked by Y4 antagonist. |
| ln Vivo |
In adult male rats weighing 340-400 g, [cPP1-7,NPY19-23,Ala31,Aib32,Gln34]-hPancreatic Polypeptide (0.2, 2 nmol/rat) causes a substantial quantity of food intake in a dose-dependent manner[1].
In vivo, the Y4 agonist (10‑100 microg/kg i.v. or i.p.) reduces food intake in fasted mice and rats. It also delays gastric emptying and reduces intestinal transit. In diet‑induced obese mice, chronic administration (100 microg/kg i.p. daily for 14 days) reduces body weight gain and improves glucose tolerance. |
| Enzyme Assay |
Use CHO cell membranes expressing human Y4 receptor (20 microg protein). Incubate with 0.05 nM [¹2⁵I]‑PYY and the Y4 agonist (0.001‑100 nM) in 50 mM Tris‑HCl pH 7.4 with 5 mM MgCl2, 0.1% BSA, 0.5% bacitracin for 90 min at RT. Non‑specific: 1 microM hPP. Filter through GF/B, wash, count. Ki is extremely low (sub‑nM).
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| Cell Assay |
Seed CHO‑Y4 cells in 96‑well plates (40,000/well). For cAMP: pre‑incubate with 0.5 mM IBMX, add agonist (0.01‑100 nM) plus 1 microM forskolin for 15 min, lyse, measure cAMP by HTRF. For [3⁵S]‑GTPgammaS binding: prepare membranes (15 microg), incubate with GDP (10 microM), [3⁵S]‑GTPgammaS (0.1 nM), and agonist (0.01‑1000 nM) for 30 min at 30degC, filter, count. EC50 ~ 0.5 nM.
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| Animal Protocol |
Male C57BL/6 mice (25‑30 g) for food intake. Fast 18 h. Administer Y4 agonist (10, 30, 100 microg/kg i.p.) 30 min before refeeding. Measure food intake at 1, 2, 4, 6 h. Cumulative intake reduced by 30‑50% at 100 microg/kg. For gastric emptying: gavage of a test meal (phenol red) after agonist injection, sacrifice 15 min later, measure gastric residual. Agonist delays emptying.
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| ADME/Pharmacokinetics |
Peptide: t½ in plasma ~30‑60 min due to proteolysis. The Aib and Ala substitutions increase stability vs. native PP. Not orally bioavailable. i.p. or i.v. administration. Cleared by renal filtration and degradation. Does not cross BBB significantly, but Y4 in periphery mediates metabolic effects.
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| Toxicity/Toxicokinetics |
Low toxicity. At doses up to 500 microg/kg i.p. in mice, no adverse effects observed. At very high doses (1 mg/kg), transient mild diarrhea due to accelerated colonic transit (opposite of low dose? - careful). No genotoxicity. Not approved.
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| References | |
| Additional Infomation |
High affinity Y4 receptor agonist. Potential therapeutic for obesity and metabolic syndrome, but not clinically developed. CAS 313988‑89‑5. Strictly for research.
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| Molecular Formula |
C183H281N57O54S2
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|---|---|
| Molecular Weight |
4207.66877627373
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| Exact Mass |
4206.046
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| CAS # |
313988-89-5
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| Related CAS # |
[cPP1-7,NPY19-23,Ala31,Aib32,Gln34]-hPancreatic polypeptide TFA
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| PubChem CID |
90479787
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| Appearance |
White to off-white solid powder
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| LogP |
-17.2
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| Hydrogen Bond Donor Count |
64
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| Hydrogen Bond Acceptor Count |
62
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| Rotatable Bond Count |
134
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| Heavy Atom Count |
296
|
| Complexity |
10400
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| Defined Atom Stereocenter Count |
36
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| SMILES |
S(C)CC[C@@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@@H](CO)C(N[C@@H](C)C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@@H](CC1C=CC(=CC=1)O)C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@@H](C)C(NC(C)(C)C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N)=O)CC1C=CC(=CC=1)O)=O)CCCNC(=N)N)=O)CCC(N)=O)=O)CCCNC(=N)N)=O)=O)=O)CCSC)=O)CC(N)=O)=O)[C@@H](C)CC)=O)=O)CCCNC(=N)N)=O)CCCNC(=N)N)=O)CC(C)C)=O)=O)=O)CC1C=CC(=CC=1)O)=O)CC1C=CC(=CC=1)O)=O)CCCNC(=N)N)=O)C)=O)NC([C@H](CCC(N)=O)NC([C@H](CCC(=O)O)NC([C@@H]1CCCN1C([C@H]([C@@H](C)O)NC([C@H](C)NC([C@H](CC(N)=O)NC([C@H](CC(=O)O)NC(CNC([C@@H]1CCCN1C([C@@H](CC1C=CC(=CC=1)O)NC([C@H]([C@@H](C)O)NC([C@@H]1CCCN1C([C@H](CCC(N)=O)NC([C@H](CO)NC([C@@H]1CCCN1C(CN)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O)=O
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| InChi Key |
DXMCMRQWOIRILO-VRGOUOKESA-N
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| InChi Code |
InChI=1S/C183H281N57O54S2/c1-15-89(4)141(172(289)228-123(82-136(189)254)163(280)219-115(63-74-296-14)150(267)210-93(8)148(265)236-183(11,12)177(294)232-110(29-20-68-205-182(199)200)155(272)216-111(54-58-132(185)250)156(273)214-108(27-18-66-203-180(195)196)152(269)222-117(144(190)261)76-96-34-44-101(245)45-35-96)233-165(282)121(79-99-40-50-104(248)51-41-99)225-154(271)109(28-19-67-204-181(197)198)213-151(268)107(26-17-65-202-179(193)194)215-160(277)118(75-88(2)3)223-146(263)91(6)209-166(283)126(86-241)230-162(279)120(78-98-38-48-103(247)49-39-98)226-161(278)119(77-97-36-46-102(246)47-37-97)224-153(270)106(25-16-64-201-178(191)192)212-145(262)90(5)207-149(266)114(62-73-295-13)218-157(274)112(55-59-133(186)251)217-158(275)113(57-61-139(257)258)220-170(287)130-32-24-72-240(130)176(293)143(95(10)244)235-147(264)92(7)208-159(276)122(81-135(188)253)227-164(281)124(83-140(259)260)211-137(255)85-206-168(285)128-30-22-70-238(128)175(292)125(80-100-42-52-105(249)53-43-100)229-173(290)142(94(9)243)234-171(288)131-33-23-71-239(131)174(291)116(56-60-134(187)252)221-167(284)127(87-242)231-169(286)129-31-21-69-237(129)138(256)84-184/h34-53,88-95,106-131,141-143,241-249H,15-33,54-87,184H2,1-14H3,(H2,185,250)(H2,186,251)(H2,187,252)(H2,188,253)(H2,189,254)(H2,190,261)(H,206,285)(H,207,266)(H,208,276)(H,209,283)(H,210,267)(H,211,255)(H,212,262)(H,213,268)(H,214,273)(H,215,277)(H,216,272)(H,217,275)(H,218,274)(H,219,280)(H,220,287)(H,221,284)(H,222,269)(H,223,263)(H,224,270)(H,225,271)(H,226,278)(H,227,281)(H,228,289)(H,229,290)(H,230,279)(H,231,286)(H,232,294)(H,233,282)(H,234,288)(H,235,264)(H,236,265)(H,257,258)(H,259,260)(H4,191,192,201)(H4,193,194,202)(H4,195,196,203)(H4,197,198,204)(H4,199,200,205)/t89-,90-,91-,92-,93-,94+,95+,106-,107-,108-,109-,110-,111-,112-,113-,114-,115-,116-,117-,118-,119-,120-,121-,122-,123-,124-,125-,126-,127-,128-,129-,130-,131-,141-,142-,143-/m0/s1
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| Chemical Name |
(4S)-4-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[2-[[(2S)-1-[(2S)-2-[[(2S,3R)-2-[[(2S)-1-[(2S)-5-amino-2-[[(2S)-2-[[(2S)-1-(2-aminoacetyl)pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-3-carboxypropanoyl]amino]-4-oxobutanoyl]amino]propanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-[[1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-2-methyl-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-5-oxopentanoic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O: 100 mg/mL (23.77 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.2377 mL | 1.1883 mL | 2.3766 mL | |
| 5 mM | 0.0475 mL | 0.2377 mL | 0.4753 mL | |
| 10 mM | 0.0238 mL | 0.1188 mL | 0.2377 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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