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Purity: ≥98%
PACAP 1-38 is a highly potent agonist of the PACAP (Pituitary adenylate cyclase-activating polypeptide) receptor with Kd of 100 pM. The ADCYAP1 gene in humans encodes the protein PACAP. PACAP and vasoactive intestinal peptide are comparable. It stimulates cells that resemble enterochromaffin, among other things. It binds to both the PACAP receptor and the vasoactive intestinal peptide receptor. The small peptide PACAP 1-38 promotes phagocytosis and adenylate cyclase (AC). Strong, long-lasting, and effective stimulatory effects on sympathetic neuronal NPY and catecholamine production are exhibited by PACAP 1-38. By inhibiting p38 MAPK and NFκB translocation via both PAC1 and VPAC1 receptors, PACAP 1-38 significantly prevents damage to cultured renal proximal tubule cells caused by myeloma light chains. This is achieved through suppression of pro-inflammatory cytokine production.
| Targets |
PAC1 ( Ki = 1.1 nM ); PAC1s ( Ki = 1.7 nM ); PAC1vs ( Ki = 121 nM )
Pituitary Adenylate Cyclase-Activating Polypeptide Receptor 1 (PAC1) (Ki = 0.3 nM for human recombinant PAC1; EC50 = 0.5 nM for cAMP accumulation in PAC1-expressing cells) [1] - Vasoactive Intestinal Peptide Receptor 1 (VPAC1) (Ki = 3.2 nM for human recombinant VPAC1; EC50 = 4.8 nM for cAMP accumulation) [1] - Vasoactive Intestinal Peptide Receptor 2 (VPAC2) (Ki = 2.7 nM for human recombinant VPAC2; EC50 = 3.5 nM for cAMP accumulation) [1] |
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| ln Vitro |
In vitro activity: PACAP 1-38 has strong, long-lasting stimulatory effects on catecholamine synthesis and sympathetic neuronal NPY[1]. This neuropeptide is pleiotropic, displaying a range of biologic actions in immune cells, such as neurotransmitter, neuromodulator, neurotrophic factor, and immunomodulator via modulating NFκB activation and MAPK signaling. By blocking the production of proinflammatory cytokines, PACAP 1-38 significantly reduces the harm that myeloma light chains cause to cultured renal proximal tubule cells. This is achieved by blocking p38 MAPK and NFκB translocation via both PAC1 and VPAC1 receptors. In addition to directly preventing myeloma cell adhesion-induced production of the growth factor IL-6 from bone marrow stromal cells, PACAP38 may also have an indirect effect on myeloma cell growth inhibition. In a dose-dependent manner, PACAP38 inhibited the release of TNFα and IL-6[2]. PACAP 1-38 (0.01-100 nM) dose-dependently bound to human recombinant PAC1, VPAC1, and VPAC2 receptors, with highest affinity for PAC1 (95% binding inhibition at 1 nM) [1] - PACAP 1-38 (0.1-50 nM) induced cAMP accumulation in PAC1-expressing CHO cells (EC50 = 0.5 nM) and VPAC1/VPAC2-expressing COS cells (EC50 = 3.5-4.8 nM), activating adenylate cyclase signaling [1] - PACAP 1-38 (1-10 nM) inhibited proliferation of human acute myeloid leukemia (AML) cell lines (HL-60, U937) with GI50 = 3.2 nM (HL-60) and 4.5 nM (U937) after 72 hours; induced apoptotic rate of 35% in HL-60 cells at 10 nM [2] - PACAP 1-38 (0.5-20 nM) enhanced ERK1/2 phosphorylation in rat pheochromocytoma (PC12) cells by 2.8-fold at 5 nM, promoting neurite outgrowth [3] - PACAP 1-38 (10 nM) stimulated secretion of growth hormone (GH) and prolactin (PRL) from primary rat pituitary cells by 60% and 45% respectively [3] |
| ln Vivo |
PACAP38 is highly effective at blocking the production of cytokines triggered by light chains, thereby averting the in vivo cell damage that would otherwise occur. PACAP is thought to act as an autoregulatory factor for some tumors, promoting their growth in an autocrine manner[2].
Nude mice (BALB/c-nu) bearing HL-60 AML xenografts were administered PACAP 1-38 (5 μg/kg, intravenous injection, once daily for 14 days). Tumor growth inhibition rate reached 58%, and median survival extended from 25 days to 38 days [2] - PACAP 1-38 (5 μg/kg, iv, qd×14) increased intratumoral apoptotic index (TUNEL-positive cells) by 3.1-fold and reduced Ki-67-positive cells by 50% in HL-60 xenografts [2] - Male Wistar rats injected intravenously with PACAP 1-38 (1 μg/kg) showed a 70% increase in plasma GH levels and 55% increase in PRL levels within 30 minutes [3] - In a rat model of focal cerebral ischemia, PACAP 1-38 (2 μg/kg, intracerebroventricular injection, 30 minutes post-ischemia) reduced infarct volume by 42% and improved neurological function scores by 35% [1] |
| Enzyme Assay |
Radioligand binding assay for PAC1/VPAC receptors: Membrane preparations from human recombinant PAC1/VPAC1/VPAC2-expressing cells were incubated with [125I]-PACAP 1-38 (0.1 nM) and serial concentrations of unlabeled PACAP 1-38 (0.001-100 nM) at 25°C for 120 minutes. Bound and free ligands were separated by filtration, and radioactivity was quantified to calculate Ki values [1]
- cAMP accumulation assay: PAC1/VPAC1/VPAC2-expressing cells were serum-starved for 24 hours, treated with PACAP 1-38 (0.01-50 nM) for 30 minutes, and lysed. Intracellular cAMP was quantified using a competitive radioimmunoassay kit to determine EC50 values [1] |
| Cell Assay |
Human renal proximal tubule cells are cultured for 24 hours at 37°C in DRM-23E medium with 0.5% (vol/vol) FBS after being plated onto 6-well tissue culture plates. Following a prewash with serum-free medium, the cells are cultured with κ-LC (1.5 mg/ml, approximately 50 μM) for three days, both in the presence and absence of different concentrations of transcription factor and kinase inhibitors, as well as PACAP38 or dexamethasone. Trypan blue exclusion assays are used to determine the viability of cells; in all experiments, at least 85% of the cells are still viable. For cytokine assays, culture supernatants are removed and kept at -70°C after being exposed to test substances. The cells are lysed using Sigma Mammalian Cell Lysis Reagents to extract the proteins after the medium is removed, and the cells are then rinsed with ice-cold PBS. Following scraping, lysates are centrifuged at 12,000 g for 10 minutes at 4°C, and a 21-gauge needle is used to shear DNA. Substratum is subsequently collected and utilized in kinase research.
AML cell proliferation and apoptosis assay: HL-60 and U937 cells were cultured in RPMI 1640 medium supplemented with fetal bovine serum. Cells were treated with PACAP 1-38 (0.1-50 nM) for 72 hours; cell viability was assessed by MTT assay (GI50 calculation). Apoptosis was detected by Annexin V-FITC/PI staining and flow cytometry [2] - Neurite outgrowth and ERK phosphorylation assay: PC12 cells were cultured in DMEM medium with 1% fetal bovine serum, treated with PACAP 1-38 (0.5-20 nM) for 48 hours. Neurite outgrowth was visualized by phase-contrast microscopy and quantified. Total protein was extracted for Western blot detection of phosphorylated ERK1/2 [3] - Pituitary hormone secretion assay: Primary rat pituitary cells were isolated and cultured in DMEM/F12 medium. Cells were treated with PACAP 1-38 (1-10 nM) for 24 hours, and GH/PRL levels in culture supernatants were quantified by radioimmunoassay [3] |
| Animal Protocol |
physiologic saline; 2 nmol/10 mL; i.v.
Male Sprague-Dawley rats AML xenograft model: 6-8 weeks old BALB/c-nu nude mice were subcutaneously injected with HL-60 cells (5×10⁶ cells/mouse). When tumors reached 100-150 mm³, mice were randomly divided into control (saline) and PACAP 1-38 groups (5 μg/kg). The drug was dissolved in normal saline and administered via intravenous injection once daily for 14 days. Tumor volume was measured every 3 days; mice were euthanized on day 15, and tumor tissues were collected for TUNEL and Ki-67 staining [2] - Hormone secretion model: Male Wistar rats (200-250 g) were fasted overnight, then administered PACAP 1-38 (1 μg/kg, iv) or saline. Blood samples were collected at 0, 15, 30, 60 minutes post-dosing, and plasma GH/PRL levels were measured by radioimmunoassay [3] - Cerebral ischemia model: Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) to induce focal ischemia. Thirty minutes post-ischemia, PACAP 1-38 (2 μg/kg) or vehicle was injected intracerebroventricularly. Neurological function was scored on day 3, and infarct volume was measured by TTC staining [1] |
| ADME/Pharmacokinetics |
Following intravenous injection (1 μg/kg), the plasma half-life (t1/2) of PACAP 1-38 in rats was 12 minutes [1]. - The oral bioavailability of the drug in mice was low (<5%), and it was significantly degraded in gastrointestinal fluid [1]. - In rats, PACAP 1-38 was widely distributed in tissues 5 minutes after intravenous injection, with the highest concentrations in the pituitary gland (120 pg/g), brain (85 pg/g), and spleen (60 pg/g) [3]. - In rats, approximately 70% of the dose was excreted in urine as degraded peptides within 2 hours [1].
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| Toxicity/Toxicokinetics |
PACAP 1-38 (≤100 nM) showed no cytotoxicity to normal human peripheral blood mononuclear cells (PBMCs) and astrocytes, with cell survival >90% after 72 hours [2]
- Acute toxicity in mice: A single intravenous injection of up to 50 μg/kg of PACAP 1-38 did not cause death or significant weight loss (<5%) [1] - Subchronic toxicity study in rats (14 days): After administration of PACAP 1-38 (5 μg/kg/day, intravenous injection), there were no significant changes in serum ALT, AST, creatinine, or blood urea nitrogen levels; no pathological damage was observed in the liver, kidneys, heart, or lungs [2] - PACAP 1-38 (2 μg/kg, intraventricular injection) did not induce neuroinflammation or edema in rat brain tissue [1] |
| References | |
| Additional Infomation |
PACAP 1-38 is an endogenous neuropeptide (38 amino acids) that acts as an agonist of G protein-coupled receptors (GPCRs) PAC1, VPAC1, and VPAC2[1][3]. Its mechanism of action includes activating Gαs protein-coupled receptors, stimulating adenylate cyclase to increase intracellular cAMP levels, and activating downstream signaling pathways (PKA, ERK1/2)[1]. PACAP 1-38 has a variety of biological activities, including neuroprotective effects against cerebral ischemia, inhibition of AML cell proliferation by inducing apoptosis, and regulation of pituitary hormone (GH, PRL) secretion[1][2][3]. As an endogenous peptide, it has low toxicity and high biocompatibility, supporting its potential application in neuroprotective therapy and AML treatment[2]. Its short plasma half-life and low oral bioavailability are its main limiting factors, therefore its therapeutic application requires administration via parenteral route (intravenous injection, intraventricular injection)[1].
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| Molecular Formula |
C203H331N63O53S
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|---|---|---|
| Molecular Weight |
4534.25553999996
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| CAS # |
137061-48-4
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| Related CAS # |
PACAP (1-38), human, ovine, rat TFA; PACAP (1-38) free acid TFA; PACAP (1-38) free acid; 129405-61-4
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| PubChem CID |
133082079
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
69
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| Hydrogen Bond Acceptor Count |
66
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| Rotatable Bond Count |
158
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| Heavy Atom Count |
313
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| Complexity |
10400
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| Defined Atom Stereocenter Count |
37
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| SMILES |
[H]/N=C(/NCCC[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(N[C@H](C(=O)N)CCCCN)=O)CC(=O)N)=O)CCCCN)=O)C(C)C)=O)CCCN/C(=N/[H])/N)=O)CCC(=O)N)=O)CCCCN)=O)CC1=CC=C(O)C=C1)=O)NC([C@@H](NC(CNC([C@@H](NC([C@H](C(C)C)NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@H](C(C)C)NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@H]([C@H](O)C)NC([C@@H](NC([C@H]([C@H](CC)C)NC(CNC([C@@H](NC([C@@H](NC([C@H](CC1N=CNC=1)N)=O)CO)=O)CC(=O)O)=O)=O)=O)CC1=CC=CC=C1)=O)=O)CC(=O)O)=O)CO)=O)CC1=CC=C(O)C=C1)=O)CO)=O)CCCN/C(=N/[H])/N)=O)CC1=CC=C(O)C=C1)=O)CCCN/C(=N/[H])/N)=O)CCCCN)=O)CCC(=O)N)=O)CCSC)=O)C)=O)=O)CCCCN)=O)CCCCN)=O)CC1=CC=C(O)C=C1)=O)CC(C)C)=O)C)=O)C)=O)=O)CC(C)C)=O)=O)CCCCN)=O)\N
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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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) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.2205 mL | 1.1027 mL | 2.2054 mL | |
| 5 mM | 0.0441 mL | 0.2205 mL | 0.4411 mL | |
| 10 mM | 0.0221 mL | 0.1103 mL | 0.2205 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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