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MedKoo Cat#: 532465 | Name: PF-3644022
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

PF-3644022 is a potent, ATP-competitive inhibitor of mitogen-activated protein kinase (MAPK)-activated protein kinase-2 (MK2) (IC50 = 5.2 nM; Ki = 3 nM). PF-3644022 inhibits tumor necrosis factor α (TNFα) production in U937 monocytic cells and peripheral blood mononuclear cells (PBMCs) (IC50 = 160 nM).

Chemical Structure

PF-3644022
PF-3644022
CAS#1276121-88-0

Theoretical Analysis

MedKoo Cat#: 532465

Name: PF-3644022

CAS#: 1276121-88-0

Chemical Formula: C21H18N4OS

Exact Mass: 374.1201

Molecular Weight: 374.46

Elemental Analysis: C, 67.36; H, 4.85; N, 14.96; O, 4.27; S, 8.56

Price and Availability

Size Price Availability Quantity
5mg USD 250.00 2 Weeks
10mg USD 450.00 2 Weeks
50mg USD 1,150.00 2 Weeks
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Related CAS #
No Data
Synonym
PF-3644022; PF 3644022; PF3644022.
IUPAC/Chemical Name
(15R)-15-methyl-5-(6-methylpyridin-3-yl)-11-thia-6,14,17-triazatetracyclo[8.8.0.0^{2,7}.0^{12,18}]octadeca-1(10),2,4,6,8,12(18)-hexaen-13-one
InChi Key
CMWRPDHVGMHLSZ-GFCCVEGCSA-N
InChi Code
InChI=1S/C21H18N4OS/c1-11-3-4-13(10-22-11)15-6-5-14-16(25-15)7-8-17-18(14)19-20(27-17)21(26)24-12(2)9-23-19/h3-8,10,12,23H,9H2,1-2H3,(H,24,26)/t12-/m1/s1
SMILES Code
O=C1C2=C(C3=C(S2)C=CC4=NC(C5=CC=C(C)N=C5)=CC=C34)NC[C@@H](C)N1
Appearance
Solid powder
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
More Info
Product Data
Product Data
Instruction
View handling instruction
Biological target:
PF-3644022 is a potent, selective, orally active and ATP-competitive MAPKAPK2 (MK2) inhibitor with an IC50 of 5.2 nM and a Ki of 3 nM.
In vitro activity:
PF-3644022 is a potent freely reversible ATP-competitive compound that inhibits MK2 activity (K(i) = 3 nM) with good selectivity when profiled against 200 human kinases. In the human U937 monocytic cell line or peripheral blood mononuclear cells, PF-3644022 potently inhibits TNFalpha production with similar activity (IC(50) = 160 nM). PF-3644022 blocks TNFalpha and IL-6 production in LPS-stimulated human whole blood with IC(50) values of 1.6 and 10.3 microM, respectively. Inhibition of TNFalpha in U937 cells and blood correlates closely with inhibition of phospho-heat shock protein 27, a target biomarker of MK2 activity. Reference: J Pharmacol Exp Ther. 2010 Jun;333(3):797-807. https://pubmed.ncbi.nlm.nih.gov/20237073/
In vivo activity:
Western blot and Real-time PCR showed that the expressions of iNOS and Arg-1 in the compressed spinal cord of twy/twy mice were significantly higher than those of the control group. After treatment with PF-3644022, the expression of Arg1 was increased while that of iNOS decreased. Realtime PCR revealed the increased expressions of inflammation related factors (such as IL-1β, NF-κB, TNF-α, MK2) and pro-apoptotic gene (Bax) except the decreased expression of anti-apoptotic gene (Bcl-2). Nevertheless, such increases were vanished after treatment of PF-3644022 except an increased expression of Bcl-2. The BMS score showed a reduced motor function of the twy/twy mice. The motor function was enhanced again with the treatment of PF-3644022. Reference: Ann Palliat Med. 2021 Feb;10(2):1304-1312. https://pubmed.ncbi.nlm.nih.gov/33040559/
Solvent mg/mL mM comments
Solubility
DMSO 43.9 117.19
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 374.46 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.

Recalculate based on batch purity %
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. Mourey RJ, Burnette BL, Brustkern SJ, Daniels JS, Hirsch JL, Hood WF, Meyers MJ, Mnich SJ, Pierce BS, Saabye MJ, Schindler JF, South SA, Webb EG, Zhang J, Anderson DR. A benzothiophene inhibitor of mitogen-activated protein kinase-activated protein kinase 2 inhibits tumor necrosis factor alpha production and has oral anti-inflammatory efficacy in acute and chronic models of inflammation. J Pharmacol Exp Ther. 2010 Jun;333(3):797-807. doi: 10.1124/jpet.110.166173. Epub 2010 Mar 17. PMID: 20237073. 2. Yu L, Song H, Fang X, Hu Y. Role of MK2 signaling pathway mediating microglia/macrophages polarization in chronic compression injury of cervical spinal cord. Ann Palliat Med. 2021 Feb;10(2):1304-1312. doi: 10.21037/apm-20-396. Epub 2020 Sep 24. PMID: 33040559. 3. Song H, Fang X, Wen M, Yu F, Gao K, Sun C, Wang Z. Role of MK2 signaling pathway in the chronic compression of cervical spinal cord. Am J Transl Res. 2015 Nov 15;7(11):2355-63. PMID: 26807183; PMCID: PMC4697715.
In vitro protocol:
1. Mourey RJ, Burnette BL, Brustkern SJ, Daniels JS, Hirsch JL, Hood WF, Meyers MJ, Mnich SJ, Pierce BS, Saabye MJ, Schindler JF, South SA, Webb EG, Zhang J, Anderson DR. A benzothiophene inhibitor of mitogen-activated protein kinase-activated protein kinase 2 inhibits tumor necrosis factor alpha production and has oral anti-inflammatory efficacy in acute and chronic models of inflammation. J Pharmacol Exp Ther. 2010 Jun;333(3):797-807. doi: 10.1124/jpet.110.166173. Epub 2010 Mar 17. PMID: 20237073.
In vivo protocol:
1. Yu L, Song H, Fang X, Hu Y. Role of MK2 signaling pathway mediating microglia/macrophages polarization in chronic compression injury of cervical spinal cord. Ann Palliat Med. 2021 Feb;10(2):1304-1312. doi: 10.21037/apm-20-396. Epub 2020 Sep 24. PMID: 33040559. 2. Song H, Fang X, Wen M, Yu F, Gao K, Sun C, Wang Z. Role of MK2 signaling pathway in the chronic compression of cervical spinal cord. Am J Transl Res. 2015 Nov 15;7(11):2355-63. PMID: 26807183; PMCID: PMC4697715.
1: Asthana S, Pandey SK, Gautam AS, Singh RK. MK2 inhibitor PF-3644022 shows protective effect in mouse microglial N9 cell line induced with cigarette smoke extract. Chem Biol Drug Des. 2024 Jul;104(1):e14592. doi: 10.1111/cbdd.14592. PMID: 39013758. 2: Chulkina M, Rohmer C, McAninch S, Panganiban RP, Villéger R, Portolese A, Ciocirlan J, Yang W, Cohen C, Koltun W, Valentine JF, Cong Y, Yochum G, Beswick EJ, Pinchuk IV. Increased Activity of MAPKAPK2 within Mesenchymal Cells as a Target for Inflammation-Associated Fibrosis in Crohn's Disease. J Crohns Colitis. 2024 Aug 6;18(7):1147-1161. doi: 10.1093/ecco-jcc/jjae009. PMID: 38224550. 3: Tran QTN, Gan PXL, Liao W, Mok YK, Chai CLL, Wong WSF. Degradation of MK2 with natural compound andrographolide: A new modality for anti-inflammatory therapy. Pharmacol Res. 2023 Aug;194:106861. doi: 10.1016/j.phrs.2023.106861. Epub 2023 Jul 20. PMID: 37480973. 4: Yu L, Song H, Fang X, Hu Y. Role of MK2 signaling pathway mediating microglia/macrophages polarization in chronic compression injury of cervical spinal cord. Ann Palliat Med. 2021 Feb;10(2):1304-1312. doi: 10.21037/apm-20-396. Epub 2020 Sep 24. PMID: 33040559. 5: Wang J, Wang G, Cheng D, Huang S, Chang A, Tan X, Wang Q, Zhao S, Wu D, Liu AT, Yang S, Xiang R, Sun P. Her2 promotes early dissemination of breast cancer by suppressing the p38-MK2-Hsp27 pathway that is targetable by Wip1 inhibition. Oncogene. 2020 Oct;39(40):6313-6326. doi: 10.1038/s41388-020-01437-2. Epub 2020 Aug 26. PMID: 32848211; PMCID: PMC7541706. 6: Berggren KL, Restrepo Cruz S, Hixon MD, Cowan AT, Keysar SB, Craig S, James J, Barry M, Ozbun MA, Jimeno A, McCance DJ, Beswick EJ, Gan GN. MAPKAPK2 (MK2) inhibition mediates radiation-induced inflammatory cytokine production and tumor growth in head and neck squamous cell carcinoma. Oncogene. 2019 Nov;38(48):7329-7341. doi: 10.1038/s41388-019-0945-9. Epub 2019 Aug 15. PMID: 31417185; PMCID: PMC6883149. 7: Li Y, Köpper F, Dobbelstein M. Inhibition of MAPKAPK2/MK2 facilitates DNA replication upon cancer cell treatment with gemcitabine but not cisplatin. Cancer Lett. 2018 Aug 1;428:45-54. doi: 10.1016/j.canlet.2018.04.030. Epub 2018 Apr 25. PMID: 29704518. 8: Singh RK, Diwan M, Dastidar SG, Najmi AK. Differential effect of p38 and MK2 kinase inhibitors on the inflammatory and toxicity biomarkers in vitro. Hum Exp Toxicol. 2018 May;37(5):521-531. doi: 10.1177/0960327117715901. Epub 2017 Jun 20. PMID: 28629242. 9: Song H, Fang X, Wen M, Yu F, Gao K, Sun C, Wang Z. Role of MK2 signaling pathway in the chronic compression of cervical spinal cord. Am J Transl Res. 2015 Nov 15;7(11):2355-63. PMID: 26807183; PMCID: PMC4697715. 10: Mourey RJ, Burnette BL, Brustkern SJ, Daniels JS, Hirsch JL, Hood WF, Meyers MJ, Mnich SJ, Pierce BS, Saabye MJ, Schindler JF, South SA, Webb EG, Zhang J, Anderson DR. A benzothiophene inhibitor of mitogen-activated protein kinase- activated protein kinase 2 inhibits tumor necrosis factor alpha production and has oral anti-inflammatory efficacy in acute and chronic models of inflammation. J Pharmacol Exp Ther. 2010 Jun;333(3):797-807. doi: 10.1124/jpet.110.166173. Epub 2010 Mar 17. PMID: 20237073.