Synonym
PF-4840154; PF 4840154; PF4840154.
IUPAC/Chemical Name
N-benzyl-4-(2-methylpropylamino)-2-[4-(oxan-3-ylmethyl)piperazin-1-yl] pyrimidine-5-carboxamide
InChi Key
PPANZCQXFYBGHN-UHFFFAOYSA-N
InChi Code
InChI=1S/C26H38N6O2/c1-20(2)15-27-24-23(25(33)28-16-21-7-4-3-5-8-21)17-29-26(30-24)32-12-10-31(11-13-32)18-22-9-6-14-34-19-22/h3-5,7-8,17,20,22H,6,9-16,18-19H2,1-2H3,(H,28,33)(H,27,29,30)
SMILES Code
O=C(C1=CN=C(N2CCN(CC3COCCC3)CC2)N=C1NCC(C)C)NCC4=CC=CC=C4
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
Biological target:
PF-4840154 is a potent, selective agonist of the rat and human TrpA1 channel with EC50s of 97 and 23 nM.
In vitro activity:
Given the issues identified with the reference agonist Mustard Oil (MO) in screening, a new, non-covalently binding agonist was optimized and proved to be a superior agent to MO for screening purposes. Compound 16a (PF-4840154) is a potent, selective agonist of the rat and human TrpA1 channel and elicited TrpA1-mediated nocifensive behaviour in mouse.
Reference: Bioorg Med Chem Lett. 2011 Aug 15;21(16):4857-9. https://pubmed.ncbi.nlm.nih.gov/21741838/
In vivo activity:
Given the issues identified with the reference agonist Mustard Oil (MO) in screening, a new, non-covalently binding agonist was optimized and proved to be a superior agent to MO for screening purposes. Compound 16a (PF-4840154) is a potent, selective agonist of the rat and human TrpA1 channel and elicited TrpA1-mediated nocifensive behaviour in mouse.
Reference: Bioorg Med Chem Lett. 2011 Aug 15;21(16):4857-9. https://pubmed.ncbi.nlm.nih.gov/21741838/
|
Solvent |
mg/mL |
mM |
comments |
| Solubility |
| DMF |
30.0 |
64.29 |
|
| DMF:PBS (pH 7.2) (1:5) |
0.1 |
0.21 |
|
| DMSO |
35.0 |
75.01 |
|
| Ethanol |
10.0 |
21.43 |
|
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
466.63
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
Ryckmans T, Aubdool AA, Bodkin JV, Cox P, Brain SD, Dupont T, Fairman E, Hashizume Y, Ishii N, Kato T, Kitching L, Newman J, Omoto K, Rawson D, Strover J. Design and pharmacological evaluation of PF-4840154, a non-electrophilic reference agonist of the TrpA1 channel. Bioorg Med Chem Lett. 2011 Aug 15;21(16):4857-9. doi: 10.1016/j.bmcl.2011.06.035. Epub 2011 Jun 21. PMID: 21741838.
In vitro protocol:
Ryckmans T, Aubdool AA, Bodkin JV, Cox P, Brain SD, Dupont T, Fairman E, Hashizume Y, Ishii N, Kato T, Kitching L, Newman J, Omoto K, Rawson D, Strover J. Design and pharmacological evaluation of PF-4840154, a non-electrophilic reference agonist of the TrpA1 channel. Bioorg Med Chem Lett. 2011 Aug 15;21(16):4857-9. doi: 10.1016/j.bmcl.2011.06.035. Epub 2011 Jun 21. PMID: 21741838.
In vivo protocol:
Ryckmans T, Aubdool AA, Bodkin JV, Cox P, Brain SD, Dupont T, Fairman E, Hashizume Y, Ishii N, Kato T, Kitching L, Newman J, Omoto K, Rawson D, Strover J. Design and pharmacological evaluation of PF-4840154, a non-electrophilic reference agonist of the TrpA1 channel. Bioorg Med Chem Lett. 2011 Aug 15;21(16):4857-9. doi: 10.1016/j.bmcl.2011.06.035. Epub 2011 Jun 21. PMID: 21741838.
1: Hoebart C, Rojas-Galvan NS, Ciotu CI, Aykac I, Reissig LF, Weninger WJ, Kiss A, Podesser BK, Fischer MJM, Heber S. No functional TRPA1 in cardiomyocytes. Acta Physiol (Oxf). 2021 Aug;232(4):e13659. doi: 10.1111/apha.13659. Epub 2021 May 4. PMID: 33819369.
2: Samanta A, Kiselar J, Pumroy RA, Han S, Moiseenkova-Bell VY. Structural insights into the molecular mechanism of mouse TRPA1 activation and inhibition. J Gen Physiol. 2018 May 7;150(5):751-762. doi: 10.1085/jgp.201711876. Epub 2018 Apr 27. PMID: 29703838; PMCID: PMC5940248.
3: Ryckmans T, Aubdool AA, Bodkin JV, Cox P, Brain SD, Dupont T, Fairman E, Hashizume Y, Ishii N, Kato T, Kitching L, Newman J, Omoto K, Rawson D, Strover J. Design and pharmacological evaluation of PF-4840154, a non-electrophilic reference agonist of the TrpA1 channel. Bioorg Med Chem Lett. 2011 Aug 15;21(16):4857-9. doi: 10.1016/j.bmcl.2011.06.035. Epub 2011 Jun 21. PMID: 21741838.
