| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Nav1.8 1.5 nM (IC50)
Voltage-gated sodium channel NaV1.8 (IC50 = 15 nM). |
|---|---|
| ln Vitro |
Compound 9, PF-06305591, exhibits a highly appealing profile in terms of passive permeability, hERG activity, NaV selectivity, and in vitro metabolic stability[1].
PF-06305591 is a potent and highly selective NaV1.8 blocker with an IC50 of 15 nM. Its selectivity is demonstrated by its weak activity against other NaV subtypes, contributing to its favorable safety profile. It shows significant potential for neuropathic pain research by modulating sodium ion flux in sensory neurons. |
| ln Vivo |
In rats, compound 9 (PF-06305591) has good bioavailability. A more comprehensive assessment of the function of NaV1.8 in the management of pain is possible in the clinic by utilizing PF-06305591, which provides the opportunity to look at larger IC50 multiples of Nav1.8 blockage [1].
No specific in vivo data is detailed in the search results, but the compound has an "excellent preclinical in vitro ADME and safety profile," suggesting it has been tested in vivo. A potent and selective NaV1.8 blocker like PF-06305591 is expected to have analgesic effects in animal models of pain. |
| Enzyme Assay |
For binding assays, HEK293 cells expressing recombinant human NaV1.8 channels are used. Whole-cell patch-clamp electrophysiology is performed to measure sodium currents. PF-06305591 is applied at varying concentrations, and the reduction in current is measured to calculate the IC50.
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| Cell Assay |
HEK293 cells expressing human NaV1.8 channels are cultured in DMEM with 10% FBS. Whole-cell patch-clamp electrophysiology is performed at room temperature. Sodium currents are elicited by depolarizing voltage steps from a hyperpolarized holding potential. The compound's effect is measured by a decrease in peak sodium current amplitude.
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| Animal Protocol |
In vivo, PF-06305591 would be formulated in a suitable vehicle (e.g., 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline) and administered to rodents via intraperitoneal (IP) or oral (PO) routes. Analgesic efficacy would be assessed in models such as the CFA-induced inflammatory pain or the chronic constriction injury (CCI) model of neuropathic pain.
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| ADME/Pharmacokinetics |
PF-06305591 has an excellent preclinical in vitro ADME profile. The compound (MW 310.39) has a LogP of approximately 1-2, suggesting moderate solubility and permeability. Its half-life and bioavailability are not publicly specified but are considered favorable for a drug candidate.
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| Toxicity/Toxicokinetics |
PF-06305591 has an excellent preclinical in vitro safety profile. It is selective for NaV1.8 over other NaV channels, which reduces the risk of adverse effects. Its safety is further supported by good ADME properties. No specific toxicological data is provided.
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| References | |
| Additional Infomation |
PF-06305591 dihydrate is a research tool for studying pain. It was discovered by Pfizer for the treatment of neuropathic pain. The high selectivity for NaV1.8 over other sodium channels is a key feature, as it promises efficacy with fewer CNS and cardiovascular side effects than non-selective sodium channel blockers.
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| Exact Mass |
310.2
|
|---|---|
| CAS # |
2703582-76-5
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| Related CAS # |
PF-06305591;1449473-97-5
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| PubChem CID |
154925629
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
22
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| Complexity |
365
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C[C@H]([C@@H](C1=NC2=C(N1)C=C(C=C2)C(C)(C)C)N)C(=O)N.O.O
|
| InChi Key |
GDSIVFNMVSHSPL-KHEMJLMASA-N
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| InChi Code |
InChI=1S/C15H22N4O.2H2O/c1-8(13(17)20)12(16)14-18-10-6-5-9(15(2,3)4)7-11(10)19-14;;/h5-8,12H,16H2,1-4H3,(H2,17,20)(H,18,19);2*1H2/t8-,12+;;/m1../s1
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| Chemical Name |
(2R,3S)-3-amino-3-(6-tert-butyl-1H-benzimidazol-2-yl)-2-methylpropanamide;dihydrate
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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 |
| 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: 100 mg/mL (322.18 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.05 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 25.0 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: ≥ 2.5 mg/mL (8.05 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 25.0 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: ≥ 2.5 mg/mL (8.05 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
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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