| Identification | Back Directory | [Name]
N-(6-amino-5-(2-chloro-5-methoxyphenyl)pyridin-2-yl)-1-methyl-1H-pyrazole-5-carboxamide(WX150095) | [CAS]
1079400-07-9 | [Synonyms]
PF 04531083
PF-04531083 >=98% (HPLC)
N-(6-amino-5-(2-chloro-5-methoxyphenyl)pyridin-2-yl)-1-methyl-1H-pyrazole-5-carboxamide
1H-Pyrazole-5-carboxamide, N-[6-amino-5-(2-chloro-5-methoxyphenyl)-2-pyridinyl]-1-methyl-
PF04531083,inhibit,Inhibitor,Na+ channels,PF 04531083,PF-04531083,Sodium Channel,Na channels
N-(6-amino-5-(2-chloro-5-methoxyphenyl)pyridin-2-yl)-1-methyl-1H-pyrazole-5-carboxamide(WX150095) | [Molecular Formula]
C17H16ClN5O2 | [MDL Number]
MFCD28411617 | [MOL File]
1079400-07-9.mol | [Molecular Weight]
357.79 |
| Chemical Properties | Back Directory | [Boiling point ]
471.0±45.0 °C(Predicted) | [density ]
1.41±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO: 125 mg/mL (349.37 mM) | [form ]
Solid | [pka]
11.32±0.70(Predicted) | [color ]
Light yellow to yellow |
| Hazard Information | Back Directory | [Uses]
PF 04531083 is an orally active and selective NaV1.8 blocker with an IC50 of 0.7 μM. PF 04531083 is a blood-brain barrier (BBB) penetrant compound. PF 04531083 can be used for the research of respiratory system and neuropathic/inflammatory pain[1][2][3]. | [Biological Activity]
PF-04531083 is an orally availablepotent and selective sodium channel Nav1.8 blocker. PF-04531083 was designated as a potential treatment of pain. | [in vivo]
PF 04531083 (1 mg/kg, i.v.; or 2 mg/kg, p.o.) is a low clearance compound with good bioavailability ～60% in rats[2].
PF 04531083 (40 mg/kg; 1.5 h) is efficacious in the tibial nerve transection (TNT) induced mechanical allodynia model in rat[2].
PF 04531083 inhibits native tetrodotoxin-resistant (TTX-R) currents in rodent dorsal root ganglion (DRG) neurons with an IC50 of 0.54 μM[2].
PF 04531083 (40 mg/kg; 1.5 h) improves baseline breathing in Tcf4tr/+ mice[3].
PF 04531083 (30 min before test) improves behavioral abnormalities associated with Pitt-Hopkins syndrome (PTHS) in Tcf4tr/+ mice[3].
| Animal Model: | Tcf4+/+ and Tcf4tr/+ mice [3] | | Dosage: | 40 mg/kg | | Administration: | Intraperitoneal injection (i.p.), 1.5 h before test | | Result: | Decreased episodes of hyperventilation, increased the occurrence of spontaneous sighs, diminished duration of post-sigh apnea and improved the CO2 minute ventilatory response in Tcf4tr/+ mice.
Showed stable respiratory activity in Tcf4+/+ mice.
Showed a robust increase in respiratory activity (62.5% increase in minute ventilation from 3 to 7% CO2) in Tcf4tr/+ pups.
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| [IC 50]
Nav1.8 | [References]
[1] Yekkirala AS, et al. Breaking barriers to novel analgesic drug development. Nat Rev Drug Discov. 2017 Aug;16(8):545-564. DOI:10.1038/nrd.2017.87
[2] Bagal SK, et al. Discovery and Optimization of Selective Nav1.8 Modulator Series That Demonstrate Efficacy in Preclinical Models of Pain. ACS Med Chem Lett. 2015 Apr 29;6(6):650-4. DOI:10.1021/acsmedchemlett.5b00059
[3] Cleary CM, et al. Disordered breathing in a Pitt-Hopkins syndrome model involves Phox2b-expressing parafacial neurons and aberrant Nav1.8 expression. Nat Commun. 2021 Oct 13;12(1):5962. DOI:10.1038/s41467-021-26263-2 |
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