 (3-36), human Chemical Structure.png)
Physicochemical Properties
| Molecular Formula | C176H272N52O54 |
| Molecular Weight | 3980.35891914368 |
| Exact Mass | 3979.017 |
| CAS # | 126339-09-1 |
| Related CAS # | Peptide YY (PYY) (3-36), porcine TFA |
| PubChem CID | 90479816 |
| Appearance | Solid powder |
| LogP | -15.7 |
| Hydrogen Bond Donor Count | 61 |
| Hydrogen Bond Acceptor Count | 61 |
| Rotatable Bond Count | 130 |
| Heavy Atom Count | 282 |
| Complexity | 9680 |
| Defined Atom Stereocenter Count | 34 |
| SMILES | O=C([C@H](CCCCN)NC([C@H](C)N)=O)N1CCC[C@H]1C(N[C@H](C(N[C@@H](C)C(N1CCC[C@H]1C(NCC(N[C@H](C(N[C@@H](CC(=O)O)C(N[C@@H](C)C(N[C@@H](CO)C(N1CCC[C@H]1C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@@H](C)C(N[C@@H](CO)C(N[C@H](C(N[C@H](C(N[C@@H](CC1=CNC=N1)C(N[C@@H](CC1C=CC(=CC=1)O)C(N[C@H](C(N[C@@H](CC(N)=O)C(N[C@H](C(N[C@H](C(N[C@H](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)[C@@H](C)O)=O)C(C)C)=O)CC(C)C)=O)=O)CC(C)C)=O)=O)=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)CO)=O)CC(C)C)=O)CCC(=O)O)=O)CCC(=O)O)=O)=O)=O)=O)=O)CCC(=O)O)=O)=O)=O)=O)CCC(=O)O)=O |
| InChi Key | AIYOBVCUSVSXOL-NYGOYQSZSA-N |
| InChi Code | InChI=1S/C176H272N52O54/c1-84(2)67-114(155(265)202-104(27-19-61-192-174(184)185)148(258)218-121(75-98-78-190-83-196-98)160(270)217-120(74-97-39-47-102(236)48-40-97)158(268)212-115(68-85(3)4)156(266)219-122(76-131(180)238)161(271)213-117(70-87(7)8)162(272)224-138(88(9)10)168(278)225-139(93(15)232)169(279)208-106(29-21-63-194-176(188)189)145(255)204-108(49-54-130(179)237)150(260)201-103(26-18-60-191-173(182)183)146(256)210-113(140(181)250)71-94-33-41-99(233)42-34-94)214-164(274)124(80-229)221-142(252)90(12)197-153(263)118(72-95-35-43-100(234)44-36-95)216-159(269)119(73-96-37-45-101(235)46-38-96)215-147(257)105(28-20-62-193-175(186)187)203-163(273)125(81-230)222-157(267)116(69-86(5)6)211-152(262)110(52-57-135(244)245)205-151(261)111(53-58-136(246)247)207-167(277)129-32-24-66-228(129)172(282)126(82-231)223-143(253)91(13)198-154(264)123(77-137(248)249)220-149(259)107(50-55-133(240)241)200-132(239)79-195-165(275)127-30-22-64-226(127)170(280)92(14)199-144(254)109(51-56-134(242)243)206-166(276)128-31-23-65-227(128)171(281)112(25-16-17-59-177)209-141(251)89(11)178/h33-48,78,83-93,103-129,138-139,229-236H,16-32,49-77,79-82,177-178H2,1-15H3,(H2,179,237)(H2,180,238)(H2,181,250)(H,190,196)(H,195,275)(H,197,263)(H,198,264)(H,199,254)(H,200,239)(H,201,260)(H,202,265)(H,203,273)(H,204,255)(H,205,261)(H,206,276)(H,207,277)(H,208,279)(H,209,251)(H,210,256)(H,211,262)(H,212,268)(H,213,271)(H,214,274)(H,215,257)(H,216,269)(H,217,270)(H,218,258)(H,219,266)(H,220,259)(H,221,252)(H,222,267)(H,223,253)(H,224,272)(H,225,278)(H,240,241)(H,242,243)(H,244,245)(H,246,247)(H,248,249)(H4,182,183,191)(H4,184,185,192)(H4,186,187,193)(H4,188,189,194)/t89-,90-,91-,92-,93+,103-,104-,105-,106-,107-,108-,109-,110-,111-,112-,113-,114-,115-,116-,117-,118-,119-,120-,121-,122-,123-,124-,125-,126-,127-,128-,129-,138-,139-/m0/s1 |
| Chemical Name | (4S)-5-[[(2S)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-[[(2S,3R)-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]-3-hydroxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-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]-3-hydroxy-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-[[2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-2-aminopropanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-4-carboxybutanoyl]amino]propanoyl]pyrrolidine-2-carbonyl]amino]acetyl]amino]-5-oxopentanoic acid |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | Y2 receptor (selective agonist) [1] |
| ln Vitro |
Peptide YY (PYY) (3-36), a porcine Y2 receptor agonist generated by dipeptidyl peptidase-IV (DPP-IV) cleavage of the first two amino acids at the N-terminus of PYY1-36, might lower food intake Quantity[1]. PYY(3-36) (2 nmol) was incubated with 200 ng of recombinant human neprilysin (NEP) for 60 minutes, resulting in 7 ± 1% degradation. [1] PYY(3-36) (2 nmol) was incubated with 200 ng of recombinant human meprin β-subunit for 30 minutes, resulting in 53 ± 5% degradation. [1] Incubation of PYY(3-36) (2 nmol) with 1.25 mg/ml rat kidney brush border (KBB) membranes for 30 minutes resulted in approximately 82% degradation. The degradation was dose- and time-dependent. [1] Mass spectrometry analysis showed that meprin β cleaved PYY(3-36) at multiple sites: Glu10-Asp11, Asp11-Ala12, and Ala12-Ser13, generating fragments PYY(11-36), PYY(12-36), and PYY(13-36). [1] KBB membranes cleaved PYY(3-36) at sites including Glu10-Asp11 and Pro14-Glu15, generating fragments PYY(11-36) and PYY(15-36). [1] The NEP inhibitor phosphoramidon (10 nmol) attenuated NEP-induced degradation of PYY(3-36) by 95%. Phosphoramidon (100 nmol) attenuated KBB-induced degradation by 36%. [1] The meprin inhibitor actinonin (10 nmol) attenuated meprin β-induced degradation of PYY(3-36) by 96%. Actinonin (100 nmol) completely prevented KBB-induced degradation of PYY(3-36). [1] |
| ln Vivo |
Actinomycin considerably increased the duration of PYY3-36's anorexic effects in mice (50 nmol/kg) and preserved greater PYY3-36 plasma levels in comparison to PYY3-36 therapy alone [1]. In overnight-fasted male C57/BL6 mice, a single subcutaneous (sc) injection of PYY(3-36) (50 nmol/kg) significantly reduced food intake at 0-1 and 1-2 hours post-injection compared to saline control. [1] When co-administered subcutaneously with the meprin inhibitor actinonin (20 mg/kg, intraperitoneal pretreatment), PYY(3-36) (50 nmol/kg) significantly reduced food intake not only at 0-1 and 1-2 hours, but also at 2-3 and 2-4 hours post-injection, prolonging its anorectic effect. [1] Cumulative food intake over 0-6 hours was significantly reduced by PYY(3-36) (50 nmol/kg) alone. The reduction was significantly greater when PYY(3-36) was co-administered with actinonin (40 mg/kg). [1] In ad libitum fed mice during the dark phase, a lower dose of PYY(3-36) (5 nmol/kg, sc) co-administered with actinonin (40 mg/kg, ip) significantly reduced food intake at 0-1 hour post-injection. [1] In the same dark phase fed model, PYY(3-36) (5 nmol/kg, sc) co-administered with the NEP inhibitor phosphoramidon (0.75 mg/kg, ip) significantly reduced cumulative food intake over 0-4 hours post-injection. [1] Plasma levels of PYY-immunoreactivity (PYY-IR) were measured after sc injection of PYY(3-36) (50 nmol/kg) in fasted mice. Co-administration with actinonin (20 mg/kg, ip) resulted in significantly higher circulating PYY-IR levels at 20 and 60 minutes post-injection compared to PYY(3-36) alone. [1] |
| Enzyme Assay |
Degradation assay with recombinant enzymes: PYY(3-36) (2 nmol) was incubated with or without 200 ng of recombinant human NEP or 200 ng of recombinant human meprin β-subunit in a digest buffer (50 mmol/L Tris-HCl, 50 mmol/L NaCl, pH 7.5) in a total volume of 120 µL at 37°C. For inhibitor studies, 10 nmol of phosphoramidon (NEP inhibitor) or actinonin (meprin inhibitor) was included in the reaction mixture. The reaction was terminated at specified time points by adding 10 µL of 10% trifluoroacetic acid. Samples were centrifuged, and the supernatant was analyzed by reverse-phase HPLC and MALDI-ToF mass spectrometry to quantify degradation and identify cleavage products. [1] Degradation assay with kidney brush border membranes: Rat kidney brush border (KBB) membranes were prepared by homogenization and centrifugation. PYY(3-36) (2 nmol) was incubated with KBB membranes (1.25 mg/mL final concentration) in a digest buffer (300 mmol/L mannitol in 12 mmol/L HEPES, pH 7.4) at 37°C for 30 minutes. For inhibitor studies, 100 nmol of phosphoramidon or actinonin was included. After incubation, samples were centrifuged, and the supernatant was analyzed by HPLC and mass spectrometry. [1] |
| Animal Protocol |
Effect of phosphoramidon on anorectic effect in fasted mice: Adult male C57/BL6 mice (20-25 g) were overnight fasted. They were divided into four groups receiving subcutaneous (sc) injections (max volume 100 µL): 1) Saline (n=10), 2) Phosphoramidon (10 mg/kg) (n=10), 3) PYY(3-36) (50 nmol/kg in saline) (n=10), 4) PYY(3-36) (50 nmol/kg) + Phosphoramidon (10 mg/kg). Body weight and food intake were measured at specified intervals up to 24 hours. [1] Effect of actinonin on anorectic effect in fasted mice: Overnight-fasted mice were divided into six groups. They first received an intraperitoneal (ip) injection (max volume 100 µL) of vehicle (20% ethanol, 80% saline) or actinonin (20 or 40 mg/kg in vehicle). Fifteen minutes later, they received a sc injection (max volume 100 µL) of saline or PYY(3-36) (50 nmol/kg in saline). Groups: 1) Vehicle ip + Saline sc (n=11), 2) Actinonin (20 mg/kg) ip + Saline sc (n=10), 3) Actinonin (40 mg/kg) ip + Saline sc (n=9), 4) Vehicle ip + PYY(3-36) sc (n=9), 5) Actinonin (20 mg/kg) ip + PYY(3-36) sc (n=9), 6) Actinonin (40 mg/kg) ip + PYY(3-36) sc (n=8). Food intake and body weight were monitored. [1] Effect of inhibitors in fed mice during dark phase: Mice with ad libitum access to food were studied during their dark (active) phase. They were divided into six groups receiving injections: 1) Vehicle ip + Saline sc (n=8), 2) Vehicle ip + PYY(3-36) (5 nmol/kg) sc (n=8), 3) Phosphoramidon (0.75 mg/kg in vehicle) ip + PYY(3-36) (5 nmol/kg) sc (n=8), 4) Phosphoramidon ip + Saline sc (n=8), 5) Actinonin (40 mg/kg in vehicle) ip + PYY(3-36) (5 nmol/kg) sc (n=8), 6) Actinonin ip + Saline sc (n=8). Food intake was measured. [1] Pharmacokinetic study with actinonin: Overnight-fasted mice were divided into groups receiving: 1) Actinonin (20 mg/kg, ip) + Saline sc, 2) Vehicle ip + PYY(3-36) (50 nmol/kg, sc), 3) Actinonin (20 mg/kg, ip) + PYY(3-36) (50 nmol/kg, sc). Mice were culled at 20, 60, and 90 minutes after the sc injection. Blood was collected via cardiac puncture, plasma separated, and PYY-immunoreactivity levels measured by radioimmunoassay. [1] |
| ADME/Pharmacokinetics |
PYY(3-36) is rapidly degraded in vitro by the metalloendopeptidase meprin β and, to a lesser extent, by neprilysin (NEP). [1] In vivo, plasma levels of PYY-immunoreactivity following a bolus subcutaneous injection of PYY(3-36) (50 nmol/kg) in mice peaked and then declined. Co-administration of the meprin inhibitor actinonin (20 mg/kg) resulted in significantly higher plasma PYY-immunoreactivity levels at 20 and 60 minutes post-injection compared to PYY(3-36) alone, suggesting inhibition of degradation prolongs circulating levels. [1] |
| Toxicity/Toxicokinetics | The literature states that supraphysiological levels of PYY(3-36) can result in nausea in humans. [1] |
| References |
[1]. A role for metalloendopeptidases in the breakdown of the gut hormone, PYY 3-36. Endocrinology. 2011 Dec;152(12):4630-40. |
| Additional Infomation |
Peptide YY (3-36), a synthetic human PYY 3-36, is a compound being evaluated for the treatment of obesity. It reduces appetite and increases satiety in obese patients. Drug Indication Investigated for use/treatment in metabolic disease and obesity. Mechanism of Action PYY 3-36 acts via the presynaptic Y2 receptor in the ARC. It decreases neuropeptide Y (NPY) release from static hypothalamic explants and thus acts to decrease food intake. PYY(3-36) is a 36-amino acid gut hormone released postprandially from L-cells in the distal gut. It is generated from PYY(1-36) by dipeptidyl peptidase-IV (DPP-IV) cleavage of the first two N-terminal amino acids. [1] It is a selective agonist for the Y2 receptor and reduces food intake via central Y2 receptors. [1] Obese humans are sensitive to its anorectic effects, but they exhibit a blunted postprandial rise. Bariatric surgery increases circulating PYY levels. [1] Its utility as an anti-obesity therapeutic is limited by a short circulating half-life. [1] The study suggests that inhibiting its degradation by meprin β (using inhibitors like actinonin) or designing analogs resistant to meprin cleavage may be useful strategies for developing anti-obesity therapies. [1] |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.2512 mL | 1.2562 mL | 2.5123 mL | |
| 5 mM | 0.0502 mL | 0.2512 mL | 0.5025 mL | |
| 10 mM | 0.0251 mL | 0.1256 mL | 0.2512 mL |