PF-01247324
- CAS No.
- 875051-72-2
- Chemical Name:
- PF-01247324
- Synonyms
- 133786;CS-2577;PF-1247324;PF-01247324;PF01247324;PF 01247324;6-amino-N-methyl-5-(2,3,5-trichlorophenyl)picolinamide;6-AMINO-N-METHYL-5-(2,3,5-TRICHLOROPHENYL)PYRIDINE-2-CARBOXAMIDE;2-PyridinecarboxaMide, 6-aMino-N-Methyl-5-(2,3,5-trichlorophenyl)-;6-AMINO-5-(2,3,5-TRICHLORO-PHENYL)-PYRIDINE-2-CARBOXYLIC ACID METHYLAMIDE;Sodium Channel,PF 01247324,PF-01247324,Na+ channels,Na channels,PF01247324,Inhibitor,inhibit
- CBNumber:
- CB42682530
- Molecular Formula:
- C13H10Cl3N3O
- Molecular Weight:
- 330.6
- MOL File:
- 875051-72-2.mol
- MSDS File:
- SDS
- Modify Date:
- 2023/5/18 11:31:10
SAFETY
Risk and Safety Statements
| Symbol(GHS) |  GHS06 |
|---|---|
| Signal word | Danger |
| Hazard statements | H301-H315-H319-H335 |
| Precautionary statements | P301+P310+P330-P302+P352-P305+P351+P338 |
| RIDADR | UN 2811 6.1 / PGIII |
PF-01247324 price More Price(2)
PF-01247324 Chemical Properties,Uses,Production
Description
PF-01247324 is a blocker of the tetrodotoxin-resistant (TTX-R) sodium channel Nav1.8 (IC50 = 0.19 μM for human Nav1.8). It is selective for Nav1.8 over Nav1.1, Nav1.2, Nav1.5, and Nav1.7 channels (IC50s = 13, 12.8, 9, and 19 μM, respectively) as well as ether-a-go-go (ERG) potassium channels (IC50 = 30 μM). PF-01247324 blocks Nav1.8 channels in a VSP-FRET assay using HEK293 cells (IC50 = 2.6 μM). In vivo, PF-01247324 (100 mg/kg) reduces phase 2 flinching in a rat model of formalin-induced persistent pain. It increases latency to lift the inflamed paw and latency to paw withdrawal in rat models of carrageenan-induced thermal hyperalgesia and mechanical hyperalgesia induced by complete Freund''s adjuvant (CFA), respectively.
Biochem/physiol Actions
In humans, PF-01247324 [6-amino-5-(2, 3, 5-trichloro-phenyl)-pyridine-2-carboxylic acid methylamide] prevents native tetrodotoxin-resistant (TTX-R) currents in dorsal root ganglion (DRG) neurons.
Enzyme inhibitor
This novel oral NaV1.8 blocker (FW = 330.59 g/mol) attenuates nociception and neuronal excitability by selectively targeting voltage-gated sodium transporter NaV1.8, with much weaker action against NaV1.1, NaV1.2, NaV1.4, NaV1.5, NaV1.6, and NaV1.7 transporters. PF-01247324 inhibited native tetrodotoxin-resistant (TTX-R) currents in human dorsal root ganglion (DRG) neurons (IC50 = 331 nM) and in recombinantly expressed hNav 1.8 (IC50 = 196 nM), with 50-fold selectivity over recombinantly expressed TTX-R hNav 1.5 channels (IC50 ～ 10 μM) and 65-100 greater selectivity over TTX-sensitive (TTX-S) channels (IC50 ～ 10-18 μM). Native TTX-R currents in small diameter rodent DRG neurons were inhibited with an IC50 of 448 nM, and the block of both human recombinant Nav1.8 and TTX-R from rat DRG neurons was both frequency and statedependent. Unlike previously published NaV1.8 blockers, PF-01247324 demonstrates frequency-dependence, and off-target frequency-dependence at other sodium channel subtypes may reduce its selectivity window. The majority of small molecule sodium channel blockers interact at the local anesthetic binding site, which due to a high level of sequence homology across voltage-gated sodium channel subtypes seems an unlikely site for interaction of selective agents such as PF-01247324. The majority of small molecule sodium channel blockers interact at the local anesthetic binding site, which due to a high level of sequence homology across voltage-gated sodium channel subtypes seems an unlikely site for interaction of selective agents such as PF-01247324
PF-01247324 Preparation Products And Raw materials
Raw materials
Preparation Products
| Supplier | Tel | Country | ProdList | Advantage | Inquiry |
|---|---|---|---|---|---|
| ATK CHEMICAL COMPANY LIMITED | +undefined-21-51877795 | China | 32760 | 60 | Inquiry |
| InvivoChem | +1-708-310-1919 +1-13798911105 | United States | 6393 | 58 | Inquiry |
| TargetMol Chemicals Inc. | +1-781-999-5354 | United States | 19973 | 58 | Inquiry |
| ShenZhen Trendseen Biological Technology Co.,Ltd. | 13417589054 | China | 11681 | 58 | Inquiry |
| Amadis Chemical Company Limited | 571-89925085 | China | 131980 | 58 | Inquiry |
| Shanghai Hao Zhun Biological Technology Co., Ltd. | 15800340161 | CHINA | 6846 | 58 | Inquiry |
| Sigma-Aldrich | 021-61415566 800-8193336 | China | 51471 | 80 | Inquiry |
| Wuhan Topule | +86-02787215551 +86-19945035818 | China | 8213 | 58 | Inquiry |
| Shanghai Lollane Biological Technology Co.,Ltd. | 021-52996696，15000506266 15000506266 | China | 4264 | 55 | Inquiry |
| Matrix Scientific | 803 788-9494 All other calls | United States | 6655 | 80 | Inquiry |