| Size | Price | Stock | Qty |
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| Targets |
The primary targets of CP-100356 HCl are MDR1 (P-glycoprotein, P-gp) and BCRP (breast cancer resistance protein), both of which are members of the ABC transporter superfamily. The compound inhibits MDR1-mediated transport with an IC50 of 0.5 μM and BCRP-mediated transport with an IC50 of 1.5 μM in MDCKII cells. It also weakly inhibits the organic anion transporting polypeptide OATP1B1 with an IC50 of approximately 66 μM. CP-100356 HCl is devoid of inhibitory activity against MRP2 (multidrug resistance-associated protein 2) and major human cytochrome P450 enzymes (IC50 >15 μM).
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| ln Vitro |
In human MDR1-transfected MDCKII cells, CP-100356 hydrochloride (0.1-15 μM; only 30 minutes) inhibits the transport of digoxin and calcein-AM solution, with an IC50 of 0.50 μM and digoxin, respectively. CP-100356 hydrochloride (0.064–200 μM; 5 min) suppresses the toxin estrogen 17β 1.2 μM that is mediated by OATP1B1. In investigations of equilibrium inhibition using CP-100356 Hydrochloride (0-50 μM; 10-30 minutes) -D-aldehyde acid solution, the enzymatic activity of monomeric P450 inside P4503A4 is inhibited (IC50 = approximately 66 μM). No inhibition (IC50>50 μM) is observed[1].
CP-100356 HCl demonstrates potent in vitro activity against its primary targets. In human MDR1-transfected MDCKII cells, it inhibits the uptake of the P-gp substrate calcein-AM with an IC50 of 0.50 μM and the transport of digoxin with an IC50 of 1.2 μM. In BCRP-transfected MDCKII cells, it inhibits the transport of prazosin with an IC50 of 1.5 μM. The compound also inhibits OATP1B1-mediated uptake of estradiol 17β-D-glucuronide with an IC50 of approximately 66 μM. Importantly, CP-100356 HCl is devoid of inhibitory activity against MRP2 and major human CYP enzymes (IC50 >15 μM), indicating good selectivity. |
| ln Vivo |
CP-100356 Systemic exposure to fexofenadine at higher dosages (increases in Cmax and AUC at 24 mg/kg of 36 and 80 times, respectively) [1].
In vivo data for CP-100356 HCl are limited in the available literature. As an orally active inhibitor of MDR1 and BCRP, the compound is expected to modulate the pharmacokinetics of co-administered substrate drugs by inhibiting their efflux from tissues. It could potentially be used in vivo to enhance the bioavailability and tissue penetration of chemotherapeutic agents that are substrates of these transporters. However, specific in vivo efficacy data, including animal models, dosing regimens, and pharmacokinetic-pharmacodynamic relationships, are not detailed in the available sources. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for CP-100356 HCl typically involve measuring its inhibition of transporter-mediated substrate transport in cell-based systems. MDCKII cells transfected with human MDR1 or BCRP are used to assess the compound's inhibitory activity. Cells are incubated with a fluorescent or radiolabeled substrate (e.g., calcein-AM for MDR1 or prazosin for BCRP) in the presence of varying concentrations of CP-100356 HCl. After incubation, the intracellular accumulation of the substrate is measured, and the IC50 for inhibition is calculated. For OATP1B1 inhibition, similar transport assays are performed using OATP1B1-expressing cells.
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| Cell Assay |
Cellular assays for CP-100356 HCl are performed using transporter-overexpressing cell lines such as MDR1-transfected or BCRP-transfected MDCKII cells. Cells are seeded in multi-well plates and pre-treated with various concentrations of the compound. A fluorescent or radiolabeled substrate is then added, and after a defined incubation period, the cells are washed and lysed. The amount of substrate accumulated inside the cells is quantified using fluorescence spectroscopy or scintillation counting. The compound's inhibitory activity is expressed as the IC50 value for inhibiting substrate transport. In vivo animal studies with CP-100356 HCl would typically involve pharmacokinetic studies in rodents to assess its ability to modulate the tissue distribution and elimination of co-administered P-gp or BCRP substrate drugs. Animals would be administered CP-100356 HCl orally, either alone or in combination with a substrate drug. Blood and tissue samples would be collected at various time points to measure the concentrations of both the inhibitor and the substrate drug. The effects of CP-100356 HCl on the pharmacokinetic parameters (e.g., AUC, Cmax, half-life) of the substrate drug would be evaluated. However, specific protocols are not detailed in the available literature.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for CP-100356 HCl indicate that it is orally active, suggesting adequate oral bioavailability. The compound is soluble in DMSO (11.36 mg/mL, 19.03 mM) and can be formulated for in vivo administration using vehicles such as 10% DMSO in 40% PEG300, 5% Tween-80, and 45% saline, or in 10% DMSO and 90% corn oil. It is stable when stored at 4°C sealed and away from moisture, and in solution at -80°C for up to 2 years or at -20°C for up to 1 year. Detailed pharmacokinetic parameters such as half-life, clearance, and volume of distribution are not reported.
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| Toxicity/Toxicokinetics |
CP-100356 HCl is considered to have a favorable safety profile based on its selectivity for MDR1 and BCRP over other transporters and enzymes. It is devoid of inhibitory activity against MRP2 and major human cytochrome P450 enzymes, with IC50 values >15 μM. This suggests a low potential for drug-drug interactions and off-target toxicity related to CYP inhibition. The compound also shows weak inhibition of OATP1B1 (IC50 ~66 μM), indicating low potential for toxicity related to this transporter. However, comprehensive toxicology data are not publicly available for this research compound.
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| References | |
| Additional Infomation |
CP-100356 HCl is a research-grade compound not approved for clinical use. Its primary application is as a pharmacological tool for studying the role of MDR1 and BCRP in multidrug resistance. By inhibiting these transporters, the compound can sensitize drug-resistant cancer cells to chemotherapeutic agents that are substrates of MDR1 and BCRP. It is also used to investigate the role of these transporters in the pharmacokinetics and tissue distribution of drugs. The compound's selectivity over MRP2 and CYP enzymes makes it a valuable tool for dissecting the specific contributions of MDR1 and BCRP in drug transport and resistance.
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| Molecular Formula |
C31H37CLN4O6
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| Molecular Weight |
597.109
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| Exact Mass |
596.24
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| CAS # |
142715-48-8
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| Related CAS # |
142716-85-6;142715-48-8(HCl);
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| PubChem CID |
71312025
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| Appearance |
White to off-white solid powder
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| LogP |
5.187
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
42
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| Complexity |
796
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
WWCHXVYTCMPAMV-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C31H36N4O6.ClH/c1-36-24-8-7-19(13-25(24)37-2)9-11-32-31-33-23-17-29(41-6)28(40-5)16-22(23)30(34-31)35-12-10-20-14-26(38-3)27(39-4)15-21(20)18-35;/h7-8,13-17H,9-12,18H2,1-6H3,(H,32,33,34);1H
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| Chemical Name |
4-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)-N-(3,4-dimethoxyphenethyl)-6,7-dimethoxyquinazolin-2-amine hydrochloride
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| Synonyms |
CP-100356 HClCP 100356 CP-100356CP100356 CP-100356 hydrochloride
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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) |
DMSO : ~11.36 mg/mL (~19.03 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.14 mg/mL (1.91 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 11.4 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 1.14 mg/mL (1.91 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 11.4 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 1.14 mg/mL (1.91 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6747 mL | 8.3737 mL | 16.7473 mL | |
| 5 mM | 0.3349 mL | 1.6747 mL | 3.3495 mL | |
| 10 mM | 0.1675 mL | 0.8374 mL | 1.6747 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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