WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 573888
CAS#: 1883299-62-4 (free base)
Description: Brepocitinib, also known as PF-06700841, is an inhibitor of JAK1 and TYK2 kinases for potential treatment of systemic lupus erythematosus and plaque psoriasis. PF-06700841 potently inhibits TYK2/JAK2 mediated IL-12/pSTAT4 and IL-23/pSTAT3 (HWB IC50 = 65 and 120 nM, respectively). PF-06700841 improves clinical symptoms of chronic plaque psoriasis by inhibition of proinflammatory cytokines that require TYK2 and Janus kinase 1 for signal transduction.
MedKoo Cat#: 573888
Name: Brepocitinib free base
CAS#: 1883299-62-4 (free base)
Chemical Formula: C18H21F2N7O
Exact Mass: 389.1776
Molecular Weight: 389.41
Elemental Analysis: C, 55.52; H, 5.44; F, 9.76; N, 25.18; O, 4.11
Related CAS #: 2140301-96-6 (tosylate) 1883299-62-4 (free base)
Synonym: PF-06700841; PF 06700841; PF06700841; PF-6700841; PF 6700841; PF6700841; Brepocitinib free base;
IUPAC/Chemical Name: [(1S)-2,2-difluorocyclopropyl](3-{2-[(1-methyl-1Hpyrazol-4-yl)amino]pyrimidin-4-yl}-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone
InChi Key: BUWBRTXGQRBBHG-RUXDESIVSA-N
InChi Code: InChI=1S/C18H21F2N7O/c1-25-8-11(7-22-25)23-17-21-5-4-15(24-17)26-9-12-2-3-13(10-26)27(12)16(28)14-6-18(14,19)20/h4-5,7-8,12-14H,2-3,6,9-10H2,1H3,(H,21,23,24)/t12?,13?,14-/m0/s1
SMILES Code: O=C([C@H]1C(F)(F)C1)N2C3CN(C4=NC(NC5=CN(C)N=C5)=NC=C4)CC2CC3
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: >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: 2934.99.9001
| Biological target: | JAK1 and TYK2 (HWB IC50 = 65 and 120 nM, respectively). |
| In vitro activity: | PF-06700841 was assayed in a human whole blood panel to evaluate inhibition across the JAK/STAT cytokine signaling families. The IFNα/pSTAT3 HWB potency for PF-06700841 was 30 nM. PF-06700841 potently inhibits TYK2/JAK2 mediated IL-12/pSTAT4 and IL-23/pSTAT3 (HWB IC50 = 65 and 120 nM, respectively). PF-06700841 has good potency against IL6/pStat1 in the CD3+ cellular subset (IC50 = 81 nM), but lower inhibition of IL6/pSTAT3, again in the CD3+ cellular subset (IC50 = 641 nM). The mechanistic basis for the difference in potency in IL6 signaling between pStat1 and pStat3 is presently unknown. PF-06700841 also inhibits the JAK1/JAK3 driven γ-common chain cytokines, represented by IL-15/pStat5 and IL-21/ pSTAT3 with reasonable potency (HWB IC50 = 238 and 204 nM, respectively). PF-06700841 inhibits EPO/pSTAT5 (JAK2 homodimer) in HWB spiked with CD34+ progenitor cells (IC50 = 577 nM). IL10/pSTAT3 (TYK2/JAK1) and IL27/pSTAT3 (JAK1/JAK2/TYK2) are also inhibited by the compound with IC50 = 305 nM and 86 nM, respectively. (Reference: J Med Chem. 2018 Oct 11;61(19):8597-8612.) |
| In vivo activity: | Female Lewis rats immunized with complete Freund’s adjuvant were dosed orally with 3, 10, or 30 mg/kg/day of PF-06700841 or vehicle for 7 consecutive days after disease onset as measured by hind paw volume using a plethysmograph. The increase in paw volume was significantly lower and dose-dependent in PF-06700841 q.d. (3, 10, and 30 mg/kg) treated groups. The plasma concentrations in animals dosed with PF-06700841 at peak (30min) and trough (24 h) time intervals post final dose respectively were as follows (mean ± SD): 3 mg/kg, 3.54 ±0.60 μM, 0.0221 ± 0.0139 μM; 10 mg/kg, 10.95 ± 2.06 μM, 0.06 ± 0.0576 μM; and 30 mg/kg, 23.89 ± 4.12 μM, 0.06 ± 0.029 μM. (Reference: J Med Chem. 2018 Oct 11;61(19):8597-8612.) |
The following data is based on the product molecular weight 389.41 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: | Fensome A, Ambler CM, Arnold E, Banker ME, Brown MF, Chrencik J, Clark JD, Dowty ME, Efremov IV, Flick A, Gerstenberger BS, Gopalsamy A, Hayward MM, Hegen M, Hollingshead BD, Jussif J, Knafels JD, Limburg DC, Lin D, Lin TH, Pierce BS, Saiah E, Sharma R, Symanowicz PT, Telliez JB, Trujillo JI, Vajdos FF, Vincent F, Wan ZK, Xing L, Yang X, Yang X, Zhang L. Dual Inhibition of TYK2 and JAK1 for the Treatment of Autoimmune Diseases: Discovery of (( S)-2,2-Difluorocyclopropyl)((1 R,5 S)-3-(2-((1-methyl-1 H-pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone (PF-06700841). J Med Chem. 2018 Oct 11;61(19):8597-8612. doi: 10.1021/acs.jmedchem.8b00917. Epub 2018 Aug 16. PMID: 30113844. |
| In vitro protocol: | Fensome A, Ambler CM, Arnold E, Banker ME, Brown MF, Chrencik J, Clark JD, Dowty ME, Efremov IV, Flick A, Gerstenberger BS, Gopalsamy A, Hayward MM, Hegen M, Hollingshead BD, Jussif J, Knafels JD, Limburg DC, Lin D, Lin TH, Pierce BS, Saiah E, Sharma R, Symanowicz PT, Telliez JB, Trujillo JI, Vajdos FF, Vincent F, Wan ZK, Xing L, Yang X, Yang X, Zhang L. Dual Inhibition of TYK2 and JAK1 for the Treatment of Autoimmune Diseases: Discovery of (( S)-2,2-Difluorocyclopropyl)((1 R,5 S)-3-(2-((1-methyl-1 H-pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone (PF-06700841). J Med Chem. 2018 Oct 11;61(19):8597-8612. doi: 10.1021/acs.jmedchem.8b00917. Epub 2018 Aug 16. PMID: 30113844. |
| In vivo protocol: | Fensome A, Ambler CM, Arnold E, Banker ME, Brown MF, Chrencik J, Clark JD, Dowty ME, Efremov IV, Flick A, Gerstenberger BS, Gopalsamy A, Hayward MM, Hegen M, Hollingshead BD, Jussif J, Knafels JD, Limburg DC, Lin D, Lin TH, Pierce BS, Saiah E, Sharma R, Symanowicz PT, Telliez JB, Trujillo JI, Vajdos FF, Vincent F, Wan ZK, Xing L, Yang X, Yang X, Zhang L. Dual Inhibition of TYK2 and JAK1 for the Treatment of Autoimmune Diseases: Discovery of (( S)-2,2-Difluorocyclopropyl)((1 R,5 S)-3-(2-((1-methyl-1 H-pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone (PF-06700841). J Med Chem. 2018 Oct 11;61(19):8597-8612. doi: 10.1021/acs.jmedchem.8b00917. Epub 2018 Aug 16. PMID: 30113844. |
1: Forman SB, Pariser DM, Poulin Y, Vincent MS, Gilbert SA, Kieras EM, Qiu R, Yu D, Papacharalambous J, Tehlirian C, Peeva E. TYK2/JAK1 Inhibitor PF-06700841 in Patients with Plaque Psoriasis: Phase IIa, Randomized, Double-Blind, Placebo- Controlled Trial. J Invest Dermatol. 2020 Dec;140(12):2359-2370.e5. doi: 10.1016/j.jid.2020.03.962. Epub 2020 Apr 18. PMID: 32311398.
2: Banfield C, Scaramozza M, Zhang W, Kieras E, Page KM, Fensome A, Vincent M, Dowty ME, Goteti K, Winkle PJ, Peeva E. The Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a TYK2/JAK1 Inhibitor (PF-06700841) in Healthy Subjects and Patients With Plaque Psoriasis. J Clin Pharmacol. 2018 Apr;58(4):434-447. doi: 10.1002/jcph.1046. Epub 2017 Dec 21. PMID: 29266308.
3: Page KM, Suarez-Farinas M, Suprun M, Zhang W, Garcet S, Fuentes-Duculan J, Li X, Scaramozza M, Kieras E, Banfield C, Clark JD, Fensome A, Krueger JG, Peeva E. Molecular and Cellular Responses to the TYK2/JAK1 Inhibitor PF-06700841 Reveal Reduction of Skin Inflammation in Plaque Psoriasis. J Invest Dermatol. 2020 Aug;140(8):1546-1555.e4. doi: 10.1016/j.jid.2019.11.027. Epub 2020 Jan 21. PMID: 31972249.
4: Fensome A, Ambler CM, Arnold E, Banker ME, Brown MF, Chrencik J, Clark JD, Dowty ME, Efremov IV, Flick A, Gerstenberger BS, Gopalsamy A, Hayward MM, Hegen M, Hollingshead BD, Jussif J, Knafels JD, Limburg DC, Lin D, Lin TH, Pierce BS, Saiah E, Sharma R, Symanowicz PT, Telliez JB, Trujillo JI, Vajdos FF, Vincent F, Wan ZK, Xing L, Yang X, Yang X, Zhang L. Dual Inhibition of TYK2 and JAK1 for the Treatment of Autoimmune Diseases: Discovery of (( S)-2,2-Difluorocyclopropyl)((1 R,5 S)-3-(2-((1-methyl-1 H-pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone (PF-06700841). J Med Chem. 2018 Oct 11;61(19):8597-8612. doi: 10.1021/acs.jmedchem.8b00917. Epub 2018 Aug 16. PMID: 30113844.
5: Ismail FF, Sinclair R. JAK inhibition in the treatment of alopecia areata - a promising new dawn? Expert Rev Clin Pharmacol. 2020 Jan;13(1):43-51. doi: 10.1080/17512433.2020.1702878. Epub 2019 Dec 22. PMID: 31865802.
6: Montilla AM, Gómez-García F, Gómez-Arias PJ, Gay-Mimbrera J, Hernández-Parada J, Isla-Tejera B, Ruano J. Scoping Review on the Use of Drugs Targeting JAK/STAT Pathway in Atopic Dermatitis, Vitiligo, and Alopecia Areata. Dermatol Ther (Heidelb). 2019 Dec;9(4):655-683. doi: 10.1007/s13555-019-00329-y. Epub 2019 Oct 13. PMID: 31606872; PMCID: PMC6828894.
7: D'Amico F, Fiorino G, Furfaro F, Allocca M, Danese S. Janus kinase inhibitors for the treatment of inflammatory bowel diseases: developments from phase I and phase II clinical trials. Expert Opin Investig Drugs. 2018 Jul;27(7):595-599. doi: 10.1080/13543784.2018.1492547. Epub 2018 Jul 6. PMID: 29938545.
