Synonym
PF-956980; PF 956980; PF956980;
IUPAC/Chemical Name
[(3R,4R)-4-Methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl]-pyrrolidin-1-ylmethanone
InChi Key
RONMOMUOZGIDET-HIFRSBDPSA-N
InChi Code
InChI=1S/C18H26N6O/c1-13-6-10-24(18(25)23-8-3-4-9-23)11-15(13)22(2)17-14-5-7-19-16(14)20-12-21-17/h5,7,12-13,15H,3-4,6,8-11H2,1-2H3,(H,19,20,21)/t13-,15+/m1/s1
SMILES Code
O=C(N1C[C@H](N(C)C2=C3C(NC=C3)=NC=N2)[C@H](C)CC1)N4CCCC4
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
>3 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
2934.99.03.00
Biological target:
PF-00956980 is a reversible pan-JAK inhibitor with IC50 values of 2.2, 23.1 and 59.9 μM for JAK1, JAK2 and JAK3.
In vitro activity:
PF-956980 has been used previously as a JAK3-selective chemical probe in numerous cell-based experiments. Here, this study reports that not only is PF-956980 a pan-JAK ATP-competitive inhibitor but it also causes selective reduction of endogenous JAK2 and JAK3 protein levels in human primary immune cells (in a time-dependent manner), leaving the other JAK family members (JAK1 and TYK2) unchanged. This study found that PF-956980 selectively downregulated JAK2 and JAK3 mRNA, corresponding to changes observed at the protein level.
Reference: ACS Chem Biol. 2017 May 19;12(5):1183-1187. https://pubmed.ncbi.nlm.nih.gov/28318222/
Preparing Stock Solutions
The following data is based on the
product
molecular weight
342.45
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. Field SD, Arkin J, Li J, Jones LH. Selective Downregulation of JAK2 and JAK3 by an ATP-Competitive pan-JAK Inhibitor. ACS Chem Biol. 2017 May 19;12(5):1183-1187. doi: 10.1021/acschembio.7b00116. Epub 2017 Mar 22. PMID: 28318222.
2. Migita K, Izumi Y, Torigoshi T, Satomura K, Izumi M, Nishino Y, Jiuchi Y, Nakamura M, Kozuru H, Nonaka F, Eguchi K, Kawakami A, Motokawa S. Inhibition of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway in rheumatoid synovial fibroblasts using small molecule compounds. Clin Exp Immunol. 2013 Dec;174(3):356-63. doi: 10.1111/cei.12190. PMID: 23968543; PMCID: PMC3826302.
In vitro protocol:
1. Field SD, Arkin J, Li J, Jones LH. Selective Downregulation of JAK2 and JAK3 by an ATP-Competitive pan-JAK Inhibitor. ACS Chem Biol. 2017 May 19;12(5):1183-1187. doi: 10.1021/acschembio.7b00116. Epub 2017 Mar 22. PMID: 28318222.
2. Migita K, Izumi Y, Torigoshi T, Satomura K, Izumi M, Nishino Y, Jiuchi Y, Nakamura M, Kozuru H, Nonaka F, Eguchi K, Kawakami A, Motokawa S. Inhibition of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway in rheumatoid synovial fibroblasts using small molecule compounds. Clin Exp Immunol. 2013 Dec;174(3):356-63. doi: 10.1111/cei.12190. PMID: 23968543; PMCID: PMC3826302.
1: Field SD, Arkin J, Li J, Jones LH. Selective Downregulation of JAK2 and JAK3 by an ATP-Competitive pan-JAK Inhibitor. ACS Chem Biol. 2017 May 19;12(5):1183-1187. doi: 10.1021/acschembio.7b00116. Epub 2017 Mar 22. PubMed PMID: 28318222.
2: Dalmasso AP, Goldish D, Benson BA, Tsai AK, Wasiluk KR, Vercellotti GM. Interleukin-4 induces up-regulation of endothelial cell claudin-5 through activation of FoxO1: role in protection from complement-mediated injury. J Biol Chem. 2014 Jan 10;289(2):838-47. doi: 10.1074/jbc.M113.455766. Epub 2013 Nov 26. PubMed PMID: 24280217; PubMed Central PMCID: PMC3887209.
3: Migita K, Izumi Y, Torigoshi T, Satomura K, Izumi M, Nishino Y, Jiuchi Y, Nakamura M, Kozuru H, Nonaka F, Eguchi K, Kawakami A, Motokawa S. Inhibition of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway in rheumatoid synovial fibroblasts using small molecule compounds. Clin Exp Immunol. 2013 Dec;174(3):356-63. doi: 10.1111/cei.12190. PubMed PMID: 23968543; PubMed Central PMCID: PMC3826302.
4: Steele AJ, Prentice AG, Cwynarski K, Hoffbrand AV, Hart SM, Lowdell MW, Samuel ER, Wickremasinghe RG. The JAK3-selective inhibitor PF-956980 reverses the resistance to cytotoxic agents induced by interleukin-4 treatment of chronic lymphocytic leukemia cells: potential for reversal of cytoprotection by the microenvironment. Blood. 2010 Nov 25;116(22):4569-77. doi: 10.1182/blood-2009-09-245811. Epub 2010 Aug 17. PubMed PMID: 20716767.
5: Changelian PS, Moshinsky D, Kuhn CF, Flanagan ME, Munchhof MJ, Harris TM, Whipple DA, Doty JL, Sun J, Kent CR, Magnuson KS, Perregaux DG, Sawyer PS, Kudlacz EM. The specificity of JAK3 kinase inhibitors. Blood. 2008 Feb 15;111(4):2155-7. Epub 2007 Dec 19. Erratum in: Blood. 2009 Oct 1;114(14):3132. Dosage error in article text; Whipple, David A [added]. PubMed PMID: 18094329.
