Brepocitinib free base
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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.


Chemical Structure

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Brepocitinib free base
CAS# 1883299-62-4 (free base)

Theoretical Analysis

MedKoo Cat#: 573888
Name: Brepocitinib free base
CAS#: 1883299-62-4 (free base)
Chemical Formula: C18H21F2N7O
Exact Mass: 389.18
Molecular Weight: 389.410
Elemental Analysis: C, 55.52; H, 5.44; F, 9.76; N, 25.18; O, 4.11

Price and Availability

Size Price Availability Quantity
10mg USD 450 2 Weeks
25mg USD 750 2 Weeks
50mg USD 1250 2 Weeks
100mg USD 2050 2 Weeks
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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

More Info:

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.)

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
Soluble in DMSO 0.0 100.00

Preparing Stock Solutions

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.

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: 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.

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1: Guttman-Yassky E, Pavel AB, Diaz A, Zhang N, Del Duca E, Estrada Y, King B, Banerjee A, Banfield C, Cox LA, Dowty ME, Page K, Vincent MS, Zhang W, Zhu L, Peeva E. Ritlecitinib and brepocitinib demonstrate significant improvement in scalp alopecia areata biomarkers. J Allergy Clin Immunol. 2022 Apr;149(4):1318-1328. doi: 10.1016/j.jaci.2021.10.036. Epub 2021 Dec 1. PMID: 34863853.


2: King B, Guttman-Yassky E, Peeva E, Banerjee A, Sinclair R, Pavel AB, Zhu L, Cox LA, Craiglow B, Chen L, Banfield C, Page K, Zhang W, Vincent MS. A phase 2a randomized, placebo-controlled study to evaluate the efficacy and safety of the oral Janus kinase inhibitors ritlecitinib and brepocitinib in alopecia areata: 24-week results. J Am Acad Dermatol. 2021 Aug;85(2):379-387. doi: 10.1016/j.jaad.2021.03.050. Epub 2021 Mar 20. PMID: 33757798.


3: Peeva E, Guttman-Yassky E, Banerjee A, Sinclair R, Cox LA, Zhu L, Zhu H, Vincent M, King B. Maintenance, withdrawal, and re-treatment with ritlecitinib and brepocitinib in patients with alopecia areata in a single-blind extension of a phase 2a randomized clinical trial. J Am Acad Dermatol. 2022 Aug;87(2):390-393. doi: 10.1016/j.jaad.2021.12.008. Epub 2021 Dec 13. PMID: 34915057.


4: Winnette R, Banerjee A, Sikirica V, Peeva E, Wyrwich K. Characterizing the relationships between patient-reported outcomes and clinician assessments of alopecia areata in a phase 2a randomized trial of ritlecitinib and brepocitinib. J Eur Acad Dermatol Venereol. 2022 Apr;36(4):602-609. doi: 10.1111/jdv.17909. Epub 2022 Jan 25. PMID: 35000236; PMCID: PMC9303953.


5: Lé AM, Torres T. New Topical Therapies for Psoriasis. Am J Clin Dermatol. 2022 Jan;23(1):13-24. doi: 10.1007/s40257-021-00649-w. Epub 2021 Oct 27. Erratum in: Am J Clin Dermatol. 2021 Dec 14;: PMID: 34705167.


6: Lax SJ, Drucker AM. How will brepocitinib cream compare with established treatments for mild-to-moderate eczema? Br J Dermatol. 2022 Dec;187(6):838. doi: 10.1111/bjd.21880. Epub 2022 Oct 5. PMID: 36199210.


7: Hughes JH, Qiu R, Banfield C, Dowty ME, Nicholas T. Population Pharmacokinetics of Oral Brepocitinib in Healthy Volunteers and Patients. Clin Pharmacol Drug Dev. 2022 Dec;11(12):1447-1456. doi: 10.1002/cpdd.1163. Epub 2022 Aug 31. PMID: 36045513; PMCID: PMC10087980.


8: Nogueira M, Puig L, Torres T. JAK Inhibitors for Treatment of Psoriasis: Focus on Selective TYK2 Inhibitors. Drugs. 2020 Mar;80(4):341-352. doi: 10.1007/s40265-020-01261-8. PMID: 32020553.


9: Cranwell WC, Sinclair RD. Can brepocitinib be formulated into an effective topical therapy to treat mild-to-moderate chronic plaque psoriasis? Br J Dermatol. 2023 May 8:ljad157. doi: 10.1093/bjd/ljad157. Epub ahead of print. PMID: 37151092.


10: Does brepocitinib benefit patients with psoriatic arthritis? Saudi Med J. 2023 Jun;44(6):625. PMID: 37343985; PMCID: PMC10284224.


11: Nash P. Janus Kinase Inhibitors: Safety in Patients With Psoriatic Arthritis. J Rheumatol. 2022 Jun;49(6 Suppl 1):44-47. doi: 10.3899/jrheum.211329. Epub 2022 Mar 15. PMID: 35293326.


12: Danese S, Peyrin-Biroulet L. Selective Tyrosine Kinase 2 Inhibition for Treatment of Inflammatory Bowel Disease: New Hope on the Rise. Inflamm Bowel Dis. 2021 Nov 15;27(12):2023-2030. doi: 10.1093/ibd/izab135. PMID: 34089259; PMCID: PMC8599029.


13: Krueger JG, McInnes IB, Blauvelt A. Tyrosine kinase 2 and Janus kinase‒signal transducer and activator of transcription signaling and inhibition in plaque psoriasis. J Am Acad Dermatol. 2022 Jan;86(1):148-157. doi: 10.1016/j.jaad.2021.06.869. Epub 2021 Jul 2. PMID: 34224773.


14: Yan D, Fan H, Chen M, Xia L, Wang S, Dong W, Wang Q, Niu S, Rao H, Chen L, Nie X, Fang Y. The efficacy and safety of JAK inhibitors for alopecia areata: A systematic review and meta-analysis of prospective studies. Front Pharmacol. 2022 Aug 24;13:950450. doi: 10.3389/fphar.2022.950450. PMID: 36091777; PMCID: PMC9449963.


15: King B, Guttman-Yassky E, Peeva E, Banerjee A, Zhu L, Zhu H, Cox LA, Vincent MS, Sinclair R. Safety and Efficacy of Ritlecitinib and Brepocitinib in Alopecia Areata: Results from the Crossover Open-Label Extension of the ALLEGRO Phase 2a Trial. JID Innov. 2022 Sep 7;2(6):100156. doi: 10.1016/j.xjidi.2022.100156. PMID: 36277481; PMCID: PMC9579791.


16: Landis MN, Arya M, Smith S, Draelos Z, Usdan L, Tarabar S, Pradhan V, Aggarwal S, Banfield C, Peeva E, Vincent MS, Sikirica V, Xenakis J, Beebe JS. Efficacy and safety of topical brepocitinib for the treatment of mild-to- moderate atopic dermatitis: a phase IIb, randomized, double-blind, vehicle- controlled, dose-ranging and parallel-group study. Br J Dermatol. 2022 Dec;187(6):878-887. doi: 10.1111/bjd.21826. Epub 2022 Oct 23. PMID: 35986699; PMCID: PMC10092158.


17: Sandborn WJ, Danese S, Leszczyszyn J, Romatowski J, Altintas E, Peeva E, Hassan-Zahraee M, Vincent MS, Reddy PS, Banfield C, Salganik M, Banerjee A, Gale JD, Hung KE. Oral Ritlecitinib and Brepocitinib for Moderate-to-Severe Ulcerative Colitis: Results From a Randomized, Phase 2b Study. Clin Gastroenterol Hepatol. 2023 Jan 6:S1542-3565(23)00007-1. doi: 10.1016/j.cgh.2022.12.029. Epub ahead of print. PMID: 36623678.


18: Gupta AK, Wang T, Polla Ravi S, Bamimore MA, Piguet V, Tosti A. Systematic review of newer agents for the management of alopecia areata in adults: Janus kinase inhibitors, biologics and phosphodiesterase-4 inhibitors. J Eur Acad Dermatol Venereol. 2023 Apr;37(4):666-679. doi: 10.1111/jdv.18810. Epub 2022 Dec 22. PMID: 36478475.


19: Martin G. Novel Therapies in Plaque Psoriasis: A Review of Tyrosine Kinase 2 Inhibitors. Dermatol Ther (Heidelb). 2023 Feb;13(2):417-435. doi: 10.1007/s13555-022-00878-9. Epub 2023 Jan 2. PMID: 36592300; PMCID: PMC9884727.


20: Landis MN, Smith SR, Berstein G, Fetterly G, Ghosh P, Feng G, Pradhan V, Aggarwal S, Banfield C, Peeva E, Vincent MS, Beebe JS, Tarabar S. Efficacy and safety of topical brepocitinib cream for mild-to-moderate chronic plaque psoriasis: a phase IIb, randomised, double-blind, vehicle-controlled, parallel- group study. Br J Dermatol. 2023 Mar 27:ljad098. doi: 10.1093/bjd/ljad098. Epub ahead of print. PMID: 36972293.