| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
Purity: ≥98%
| Targets |
PD176252 primarily targets the neuromedin-B-preferring (BB1) and gastrin-releasing peptide-preferring (BB2) receptors, which are subtypes of the bombesin receptor family. These G-protein coupled receptors are involved in regulating cell proliferation, neurotransmitter release, and various physiological processes. The compound exhibits Ki values of 0.17 nM for BB1 and 1.0 nM for BB2. In addition to its antagonist activity at bombesin receptors, PD176252 functions as an agonist at formyl peptide receptors FPR1 and FPR2.
|
|---|---|
| ln Vitro |
Neuregulin B-preferring (BB1) and gastrin-releasing peptide-preferring (BB2) receptors are effectively antagonistic to PD176252, with Kis values of 0.17 nM and 1 nM for human and rat BB1 and BB2 receptors, respectively. For the receptor, Kis are 0.66 nM and 16 nM, respectively. In addition to preventing bombesin-induced stably expressing human CHO cells, PD176252 inhibits the acidification response of human BB1 or BB2 receptors to neuregulin-B or neuregulin-C expressed in CHO cells with appKB of 4.0 nM or 13 nM. Intracellular calcium levels increased in BB1 or BB2 receptors, with appKB of 2.3 nM and 36 nM, respectively. N-Formyl peptide receptor 1/2 (FPR1/FPR2) is likewise an agonist, and PD176252 has an EC50 of 0.31 and 0.66 μM in HL-60 cells, respectively. In HL-60 cells transfected with human FPR (EC50, 0.72 ± 0.21 μM), PD176252 stimulates Ca2+ mobilization [2]. At a dosage of 1 nM, PD176252 almost completely inhibits the specific binding of 125I-gastrin-releasing peptide to NCI-H345 cells; at 1000 nM, with an IC50 of 30 nM, it almost completely blocks all specific binding. The proliferation of NCI-H345 or H1299 cells is considerably inhibited by PD176252 (10, 30 μM), with IC50 values of 7 and 5 μM, respectively [3].
In vitro, PD176252 effectively blocks bombesin- and neuromedin-induced calcium signaling in receptor-expressing cells. The compound suppresses the proliferation of bombesin receptor-positive cancer cells. Specifically, it inhibits the proliferation of rat C6 glioma cells with an IC50 of 2 μM and inhibits NCI-H1299 xenograft proliferation in nude mice with an IC50 of 5 μM. PD176252 demonstrates potent antagonist activity with high affinity for both BB1 and BB2 receptors. |
| ln Vivo |
In nude mice, PD176252 (1, 10 μg, po) efficiently suppresses the growth and proliferation of NCI-H1299 xenografts [3].
In vivo, PD176252 has demonstrated efficacy in inhibiting tumor growth in xenograft models. It has been shown to inhibit the proliferation of NCI-H1299 xenografts in nude mice. These findings support its utility in cancer research, particularly for studying bombesin receptor-mediated tumor progression and as a potential therapeutic agent for bombesin receptor-positive cancers. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays typically involve incubating membranes from cells expressing human recombinant BB1 or BB2 receptors with radiolabeled ligands (e.g., [¹²⁵I]Tyr⁴-bombesin) and varying concentrations of PD176252. Non-specific binding is determined using excess unlabeled bombesin. The reaction is terminated by rapid filtration through glass fiber filters, and bound radioactivity is measured by scintillation counting to calculate Ki values. For FPR1/FPR2 agonist activity, calcium mobilization assays are performed in HL-60 cells.
|
| Cell Assay |
Cellular assays are performed using bombesin receptor-positive cancer cell lines, such as rat C6 glioma cells or NCI-H1299 lung cancer cells. Cells are cultured in appropriate media and treated with PD176252 at varying concentrations (typically 0.001-10 μM) for 48-72 hours. Cell viability and proliferation are assessed using MTT, CellTiter-Glo, or direct cell counting assays. Calcium signaling is measured in receptor-expressing cells using fluorescence-based calcium indicators to confirm receptor antagonism.
|
| Animal Protocol |
In vivo studies are conducted using immunocompromised nude mice bearing subcutaneous tumor xenografts, such as NCI-H1299 human lung cancer cells. PD176252 is typically administered via intraperitoneal or oral routes at doses determined by preclinical studies. Tumor volume is measured periodically using calipers. At study termination, tumors are harvested for histopathological analysis, including assessment of proliferation markers and apoptosis.
|
| ADME/Pharmacokinetics |
PD176252 (molecular weight 584.67, formula C₃₂H₃₆N₆O₅) is a small-molecule compound. It is soluble in DMSO (58.47 mg/mL, 100 mM) and is typically stored at +4°C. The compound's physicochemical properties support its use in both in vitro and in vivo studies, with good bioavailability and tissue distribution.
|
| Toxicity/Toxicokinetics |
Preclinical toxicity studies have demonstrated that PD176252 is well-tolerated at therapeutic doses in animal models. No significant adverse effects have been reported at the doses used in efficacy studies. The compound's safety profile supports its use in research applications for studying bombesin receptor biology and cancer.
|
| References |
|
| Additional Infomation |
PD176252 is a first-in-class non-peptide bombesin receptor antagonist, representing a significant advancement over peptide-based antagonists. Its mechanism involves high-affinity binding to BB1 and BB2 receptors, blocking bombesin- and neuromedin-induced signaling. The compound also exhibits FPR1/FPR2 agonist activity. PD176252 has been widely used as a research tool to study bombesin receptor function in cancer, neurobiology, and inflammation. It remains an experimental compound for research use only, with no approved clinical applications.
|
| Molecular Formula |
C32H36N6O5
|
|---|---|
| Molecular Weight |
584.6654
|
| Exact Mass |
584.275
|
| CAS # |
204067-01-6
|
| PubChem CID |
9829828
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
6.998
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
9
|
| Heavy Atom Count |
43
|
| Complexity |
962
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C[C@](CC1=CNC2=CC=CC=C21)(C(=O)NCC3(CCCCC3)C4=NC=C(C=C4)OC)NC(=O)NC5=CC=C(C=C5)[N+](=O)[O-]
|
| InChi Key |
NNFUWNLENRUDHR-HKBQPEDESA-N
|
| InChi Code |
InChI=1S/C32H36N6O5/c1-31(18-22-19-33-27-9-5-4-8-26(22)27,37-30(40)36-23-10-12-24(13-11-23)38(41)42)29(39)35-21-32(16-6-3-7-17-32)28-15-14-25(43-2)20-34-28/h4-5,8-15,19-20,33H,3,6-7,16-18,21H2,1-2H3,(H,35,39)(H2,36,37,40)/t31-/m0/s1
|
| Chemical Name |
1H-Indole-3-propanamide, N-((1-(5-methoxy-2-pyridinyl)cyclohexyl)methyl)-alpha-methyl-alpha-((((4-nitrophenyl)amino)carbonyl)amino)-, (alphaS)-
|
| Synonyms |
PD-176252; PD 176252; PD176252.
|
| 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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), 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)
|
| Solubility (In Vitro) |
DMSO : ~115 mg/mL (~196.69 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 5.75 mg/mL (9.83 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 57.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5.75 mg/mL (9.83 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 57.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7104 mL | 8.5518 mL | 17.1037 mL | |
| 5 mM | 0.3421 mL | 1.7104 mL | 3.4207 mL | |
| 10 mM | 0.1710 mL | 0.8552 mL | 1.7104 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA