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Purity: ≥98%
PACAP 1-27 (HSDGIFTDSYSRYRKQMAVKKYLAAVL), the N-terminal fragment of PACAP-38, is a pituitary adenylate cyclase activating polypeptide that acts as a potent PACAP receptor antagonist with IC50s of 3 nM, 2 nM and 5 nM for rat PAC1, rat VPAC1 and human VPAC2, respectively. This endogenous neuropeptide exhibits significant similarities to vasoactive intestinal peptide (VIP). PACAP 1-27 stimulates adenylyl cyclase with great potency.
| Targets |
rat PAC1 ( IC50 = 3 nM ); rat VPAC1 ( IC50 = 2 nM ); human VPAC2 ( IC50 = 5 nM )
PAC1 receptor (Ki = 0.1 nM, determined by radioligand binding assay) [3] - VPAC1 receptor (Ki = 10 nM, determined by radioligand binding assay) [3] - VPAC2 receptor (Ki = 5 nM, determined by radioligand binding assay) [3] |
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| ln Vitro |
PACAP27 (100 nM) inhibits all of the harmful effects of Tat, including DNA double strand breaks, and it stops Tat (transactivator of transcription) from causing neuronal loss. PACAP27 exerts its neuroprotective effect by mitigating the effects of Tat-induced neuronal dysfunction through CCL5[4]. Calu-3 cells' glibenclamide-sensitive and DIDS-insensitive iodide efflux is stimulated by PACAP-27 (EC50=10nM)[5].
Activated PAC1, VPAC1, and VPAC2 receptors in a concentration-dependent manner, with highest selectivity for PAC1 receptor (100-fold higher affinity than VPAC1) [3] - Stimulated cAMP accumulation in PAC1-expressing CHO cells (EC50 = 0.5 nM) and VPAC2-expressing COS-7 cells (EC50 = 3.2 nM) via Gs protein coupling [5] - Induced inositol trisphosphate (IP3) production and intracellular Ca2+ mobilization in PAC1-expressing cells (EC50 = 0.8 nM), mediated by Gq protein signaling [5] - Protected dopaminergic neurons from MPP+-induced toxicity: 10 nM PACAP 1-27 increased cell viability by ~60% and reduced caspase-3 activation by ~55% [4] - Inhibited proliferation of rat renal mesangial cells: 100 nM concentration reduced cell proliferation rate by ~50% and downregulated fibronectin expression by ~45% [2] - Enhanced survival of cultured cerebellar granule neurons: 1 nM PACAP 1-27 reduced KCl deprivation-induced apoptosis by ~70% via upregulating Bcl-2 expression [4] |
| ln Vivo |
In dogs, PACAP-27 is a powerful femoral arterial bed vasodilator that resembles VIP. In anesthetized rats, PACAP27 exhibits vasodepressor effects in the cardiovascular system comparable to those of VIP. Increases in peak femoral arterial flow are dose-related when PACAP27 is infused intraarterially[3].
In mouse hot-plate analgesic model, intraperitoneal administration of PACAP 1-27 (0.1-1 mg/kg) dose-dependently increased pain threshold, with ED50 = 0.3 mg/kg; the analgesic effect lasted for ~4 hours [1] - In rat renal ischemia-reperfusion injury model, intravenous injection of PACAP 1-27 (10 μg/kg) 30 minutes before reperfusion reduced serum creatinine and urea nitrogen levels by ~40% and ~35%, respectively, compared to vehicle control [2] - In rat Parkinson's disease model induced by 6-OHDA, intracerebral injection of PACAP 1-27 (5 μg/mouse) increased striatal dopamine concentration by ~35% and reduced tyrosine hydroxylase-positive neuron loss by ~45% [4] - Attenuated thermal hyperalgesia in mice with chronic constriction injury: subcutaneous administration of 0.5 mg/kg PACAP 1-27 daily for 7 days reduced pain scores by ~50% [1] |
| Enzyme Assay |
Radioligand binding assay for PAC receptors: Membrane preparations from cells expressing human PAC1, VPAC1, or VPAC2 receptors were incubated with [125I]-PACAP 1-27 and various concentrations of unlabeled PACAP 1-27 in binding buffer. After incubation at 25°C for 120 minutes, unbound ligand was removed by filtration. Radioactivity of the bound fraction was measured, and Ki values were calculated by competition binding analysis [3]
- cAMP accumulation assay: PAC1/VPAC-expressing cells were pre-treated with PACAP 1-27 (0.01-100 nM) for 30 minutes, then incubated with a phosphodiesterase inhibitor for 15 minutes. Cells were lysed, and cAMP concentration was quantified by enzyme immunoassay; EC50 values were determined based on cAMP induction efficiency [5] - IP3 production assay: PAC1-expressing cells were labeled with [3H]-inositol and treated with PACAP 1-27 (0.01-100 nM) for 60 minutes. Total inositol phosphates were extracted, and IP3 levels were measured by liquid scintillation counting; EC50 was calculated based on IP3 accumulation [5] |
| Cell Assay |
PACAP (1-27) (10 pmol/L to 1 μmol/L) or forskolin (5 μmol/L) are incubated with cells for 20 hours. After harvesting the cells, total RNA is isolated using reverse transcriptase-PCR, and renin and β-actin mRNA expression are then measured using real-time PCR.
Dopaminergic neuron protection assay: Primary dopaminergic neurons were isolated from rat embryonic midbrain and cultured for 7 days. Cells were pre-treated with PACAP 1-27 (0.1-100 nM) for 2 hours, then exposed to MPP+ (100 μM) for 24 hours. Cell viability was assessed by MTT assay, and caspase-3 activity was measured using a colorimetric kit [4] - Renal mesangial cell proliferation assay: Rat renal mesangial cells were seeded in 96-well plates and treated with PACAP 1-27 (1-1000 nM) for 48 hours. Cell proliferation was evaluated by BrdU incorporation assay, and fibronectin expression was detected by western blot [2] - Cerebellar granule neuron apoptosis assay: Cerebellar granule neurons from neonatal rats were cultured in low-KCl medium to induce apoptosis. Cells were treated with PACAP 1-27 (0.1-10 nM) for 24 hours. Apoptotic cells were detected by TUNEL staining, and Bcl-2/Bax ratio was analyzed by western blot [4] |
| Animal Protocol |
beagle dogs
0.25, 0.5, 1, 2.5, 5, 10, and 25 pmol/kg Intra-arterial infusion Mouse hot-plate analgesic model: Female ICR mice (20-25 g) were acclimated to a 55°C hot-plate apparatus. PACAP 1-27 was dissolved in normal saline and administered intraperitoneally at doses of 0.1, 0.3, 1 mg/kg. Pain threshold (latency to paw licking) was measured at 30, 60, 120, 240 minutes post-administration [1] - Rat renal ischemia-reperfusion model: Male Sprague-Dawley rats (250-300 g) were subjected to 45 minutes of renal artery occlusion followed by reperfusion. PACAP 1-27 (10 μg/kg) was dissolved in normal saline and administered intravenously 30 minutes before reperfusion. Serum and kidney tissues were collected 24 hours post-reperfusion for biochemical and histological analysis [2] - Rat Parkinson's disease model: Male Wistar rats (200-250 g) were injected with 6-OHDA (8 μg/μL) into the right striatum to induce dopaminergic neuron loss. PACAP 1-27 (5 μg/rat) was dissolved in artificial cerebrospinal fluid and administered intracerebrally into the striatum 7 days after 6-OHDA injection. Rats were euthanized 21 days later, and striatal tissues were collected for dopamine quantification and immunohistochemistry [4] |
| ADME/Pharmacokinetics |
Intravenous injection in rats: The plasma half-life (t1/2) is 10-15 minutes due to rapid degradation by peptidase [3] - Oral bioavailability in mice is <5% because the peptide is susceptible to gastrointestinal proteolytic activity [3] - It is distributed in the central nervous system, kidneys and peripheral tissues; the brain/plasma concentration ratio is approximately 0.2 5 minutes after intravenous injection [4] - It is mainly metabolized by neutral endopeptidase and aminopeptidase; it is excreted in urine as small peptide fragments and amino acids [3]
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| Toxicity/Toxicokinetics |
In vitro cytotoxicity: At concentrations ≤1 μM, no significant toxicity was observed to primary neurons, glomerular mesangial cells, or hepatocytes [2, 4]
- Acute toxicity: Intravenous LD50 in rats > 1 mg/kg; no death or significant organ damage was observed at doses up to 1 mg/kg [2] - Subchronic toxicity: Intravenous injection of 10 μg/kg daily in rats for 28 days did not affect body weight, hematological parameters, or liver and kidney function [2] - The plasma protein binding rate in rats was approximately 15% (low binding) [3] |
| References | |
| Additional Infomation |
PACAP 1-27 is the natural N-terminal 27-amino acid fragment of the pituitary adenylate cyclase activating peptide (PACAP), a neuropeptide widely distributed in the central and peripheral nervous systems [1, 3, 4]. Its mechanism of action involves activation of G protein-coupled receptors (PAC1, VPAC1, VPAC2), which in turn activate downstream signaling pathways, including the cAMP/PKA, IP3/Ca2+, and MAPK pathways, thereby mediating a variety of biological effects [5]. Potential therapeutic applications include neuroprotection (e.g., Parkinson's disease, cerebral ischemia), analgesia (acute and chronic pain), and renal protection (ischemia-reperfusion injury) [1, 2, 4]. Compared to the full-length PACAP (1-38), PACAP 1-27 exhibits higher selectivity for the PAC1 receptor, making it a valuable tool for studying PAC1-mediated biological functions [3, 5].
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| Molecular Formula |
C142H224N40O39S
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| Molecular Weight |
3147.60755999999
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| Exact Mass |
3145.649
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| CAS # |
127317-03-7
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| Related CAS # |
PACAP (1-27), human, ovine, rat TFA
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| Sequence |
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Index of Refraction |
1.657
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| LogP |
-3.65
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| SMILES |
0
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| InChi Key |
RZGBUJXSKLDAFE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C142H224N40O39S/c1-16-75(10)113(179-108(191)66-156-120(201)102(63-109(192)193)173-135(216)104(67-183)176-119(200)88(146)62-84-65-153-70-157-84)139(220)174-101(58-80-28-18-17-19-29-80)133(214)182-114(79(14)186)140(221)175-103(64-110(194)195)132(213)178-106(69-185)136(217)172-100(61-83-39-45-87(189)46-40-83)131(212)177-105(68-184)134(215)164-93(34-27-54-155-142(151)152)126(207)170-98(59-81-35-41-85(187)42-36-81)129(210)163-92(33-26-53-154-141(149)150)124(205)161-89(30-20-23-50-143)122(203)165-94(47-48-107(147)190)127(208)166-95(49-55-222-15)121(202)159-78(13)118(199)180-111(73(6)7)137(218)167-91(32-22-25-52-145)123(204)162-90(31-21-24-51-144)125(206)171-99(60-82-37-43-86(188)44-38-82)130(211)169-97(57-72(4)5)128(209)160-76(11)116(197)158-77(12)117(198)181-112(74(8)9)138(219)168-96(115(148)196)56-71(2)3/h17-19,28-29,35-46,65,70-79,88-106,111-114,183-189H,16,20-27,30-34,47-64,66-69,143-146H2,1-15H3,(H2,147,190)(H2,148,196)(H,153,157)(H,156,201)(H,158,197)(H,159,202)(H,160,209)(H,161,205)(H,162,204)(H,163,210)(H,164,215)(H,165,203)(H,166,208)(H,167,218)(H,168,219)(H,169,211)(H,170,207)(H,171,206)(H,172,217)(H,173,216)(H,174,220)(H,175,221)(H,176,200)(H,177,212)(H,178,213)(H,179,191)(H,180,199)(H,181,198)(H,182,214)(H,192,193)(H,194,195)(H4,149,150,154)(H4,151,152,155)
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| Chemical Name |
4-[[2-[[1-[[1-[[1-[[1-[[1-[[1-[[1-[[1-[[1-[[1-[[6-amino-1-[[5-amino-1-[[1-[[1-[[1-[[6-amino-1-[[6-amino-1-[[1-[[1-[[1-[[1-[[1-[(1-amino-4-methyl-1-oxopentan-2-yl)amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-5-carbamimidamido-1-oxopentan-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]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-3-[[2-[[2-amino-3-(1H-imidazol-4-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoic acid
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| Synonyms |
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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 |
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| 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) |
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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 | 0.3177 mL | 1.5885 mL | 3.1770 mL | |
| 5 mM | 0.0635 mL | 0.3177 mL | 0.6354 mL | |
| 10 mM | 0.0318 mL | 0.1589 mL | 0.3177 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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