Synonym
PF-06250112; PF 06250112; PF06250112.
IUPAC/Chemical Name
1‐(1‐Cyanopiperidine‐3α‐yl)‐3‐[4‐(2,4‐difluorophenoxy)phenyl]‐5‐amino‐1H‐pyrazole‐4‐carboxamide
InChi Key
SQFDBQCBXUWICP-HNNXBMFYSA-N
InChi Code
InChI=1S/C22H20F2N6O2/c23-14-5-8-18(17(24)10-14)32-16-6-3-13(4-7-16)20-19(22(27)31)21(26)30(28-20)15-2-1-9-29(11-15)12-25/h3-8,10,15H,1-2,9,11,26H2,(H2,27,31)/t15-/m0/s1
SMILES Code
O=C(C1=C(N)N([C@@H]2CN(C#N)CCC2)N=C1C3=CC=C(OC4=CC=C(F)C=C4F)C=C3)N
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-06250112 is a potent, highly selective, orally bioavailable BTK inhibitor with an IC50 of 0.5 nM.
In vitro activity:
This study confirmed the effect of PF-06250112 on splenic B cells by monitoring the upregulation of CD86 in response to B-cell triggering with anti-IgM or anti-IgD for in vitro and in vivo assays, respectively. Pre-treatment of purified splenic B cells by PF-06250112 prevented, in a dose-dependent manner, the induction of CD86 expression on B cells upon stimulation with anti-IgM F(ab’)2 fragments (Figure 1A).
Reference: Haematologica. 2019 May;104(5):1046-1054. https://pubmed.ncbi.nlm.nih.gov/30545924/
In vivo activity:
To assess the therapeutic impact of BTK inhibition, this study treated aged NZBxW_F1 mice with PF-06250112 and demonstrate that PF-06250112 significantly limits the spontaneous accumulation of splenic germinal center B cells and plasma cells. Correspondingly, anti-dsDNA and autoantibody levels were reduced in a dose-dependent manner. Moreover, administration of PF-06250112 prevented the development of proteinuria and improved glomerular pathology scores in all treatment groups. Strikingly, this therapeutic effect could occur with only a modest reduction observed in anti-dsDNA titers, implying a critical role for BTK signaling in disease pathogenesis beyond inhibition of autoantibody production. This study subsequently demonstrates that PF-06250112 prevents proteinuria in an FcR-dependent, Ab-mediated model of glomerulonephritis.
Reference: J Immunol. 2013 Nov 1;191(9):4540-50. https://pubmed.ncbi.nlm.nih.gov/24068666/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
438.44
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:
1. Delignat S, Russick J, Gangadharan B, Rayes J, Ing M, Voorberg J, Kaveri SV, Lacroix-Desmazes S. Prevention of the anti-factor VIII memory B-cell response by inhibition of Bruton tyrosine kinase in experimental hemophilia A. Haematologica. 2019 May;104(5):1046-1054. doi: 10.3324/haematol.2018.200279. Epub 2018 Dec 13. PMID: 30545924; PMCID: PMC6518880.
2. Rankin AL, Seth N, Keegan S, Andreyeva T, Cook TA, Edmonds J, Mathialagan N, Benson MJ, Syed J, Zhan Y, Benoit SE, Miyashiro JS, Wood N, Mohan S, Peeva E, Ramaiah SK, Messing D, Homer BL, Dunussi-Joannopoulos K, Nickerson-Nutter CL, Schnute ME, Douhan J 3rd. Selective inhibition of BTK prevents murine lupus and antibody-mediated glomerulonephritis. J Immunol. 2013 Nov 1;191(9):4540-50. doi: 10.4049/jimmunol.1301553. Epub 2013 Sep 25. PMID: 24068666.
In vitro protocol:
1. Delignat S, Russick J, Gangadharan B, Rayes J, Ing M, Voorberg J, Kaveri SV, Lacroix-Desmazes S. Prevention of the anti-factor VIII memory B-cell response by inhibition of Bruton tyrosine kinase in experimental hemophilia A. Haematologica. 2019 May;104(5):1046-1054. doi: 10.3324/haematol.2018.200279. Epub 2018 Dec 13. PMID: 30545924; PMCID: PMC6518880.
2. Rankin AL, Seth N, Keegan S, Andreyeva T, Cook TA, Edmonds J, Mathialagan N, Benson MJ, Syed J, Zhan Y, Benoit SE, Miyashiro JS, Wood N, Mohan S, Peeva E, Ramaiah SK, Messing D, Homer BL, Dunussi-Joannopoulos K, Nickerson-Nutter CL, Schnute ME, Douhan J 3rd. Selective inhibition of BTK prevents murine lupus and antibody-mediated glomerulonephritis. J Immunol. 2013 Nov 1;191(9):4540-50. doi: 10.4049/jimmunol.1301553. Epub 2013 Sep 25. PMID: 24068666.
In vivo protocol:
1. Delignat S, Russick J, Gangadharan B, Rayes J, Ing M, Voorberg J, Kaveri SV, Lacroix-Desmazes S. Prevention of the anti-factor VIII memory B-cell response by inhibition of Bruton tyrosine kinase in experimental hemophilia A. Haematologica. 2019 May;104(5):1046-1054. doi: 10.3324/haematol.2018.200279. Epub 2018 Dec 13. PMID: 30545924; PMCID: PMC6518880.
2. Rankin AL, Seth N, Keegan S, Andreyeva T, Cook TA, Edmonds J, Mathialagan N, Benson MJ, Syed J, Zhan Y, Benoit SE, Miyashiro JS, Wood N, Mohan S, Peeva E, Ramaiah SK, Messing D, Homer BL, Dunussi-Joannopoulos K, Nickerson-Nutter CL, Schnute ME, Douhan J 3rd. Selective inhibition of BTK prevents murine lupus and antibody-mediated glomerulonephritis. J Immunol. 2013 Nov 1;191(9):4540-50. doi: 10.4049/jimmunol.1301553. Epub 2013 Sep 25. PMID: 24068666.
1: Paley MA, Strand V, Kim AH. From mechanism to therapies in systemic lupus erythematosus. Curr Opin Rheumatol. 2017 Mar;29(2):178-186. doi: 10.1097/BOR.0000000000000369. Review. PubMed PMID: 28118202.
2: Rankin AL, Seth N, Keegan S, Andreyeva T, Cook TA, Edmonds J, Mathialagan N, Benson MJ, Syed J, Zhan Y, Benoit SE, Miyashiro JS, Wood N, Mohan S, Peeva E, Ramaiah SK, Messing D, Homer BL, Dunussi-Joannopoulos K, Nickerson-Nutter CL, Schnute ME, Douhan J 3rd. Selective inhibition of BTK prevents murine lupus and antibody-mediated glomerulonephritis. J Immunol. 2013 Nov 1;191(9):4540-50. doi: 10.4049/jimmunol.1301553. Epub 2013 Sep 25. PubMed PMID: 24068666.
Delignat S, Russick J, Gangadharan B, Rayes J, Ing M, Voorberg J, Kaveri SV, Lacroix-Desmazes S. Prevention of the anti-factor VIII memory B-cell response by inhibition of Bruton tyrosine kinase in experimental hemophilia A. Haematologica. 2019 May;104(5):1046-1054. doi: 10.3324/haematol.2018.200279. Epub 2018 Dec 13. PMID: 30545924; PMCID: PMC6518880.
