Baricitinib free base | INCB28050 | LY3009104 | CAS#1187594-09-7 | 1187595-84-1 | JAK inhibitor

MedKoo Cat#: 205893 | Name: Baricitinib

Description:

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

Baricitinib, also known as INCB028050 or LY3009104, is a selective orally bioavailable JAK1/JAK2 inhibitor with nanomolar potency against JAK1 (5.9 nM) and JAK2 (5.7 nM). INCB028050 inhibits intracellular signaling of multiple proinflammatory cytokines including IL-6 and IL-23 at concentrations <50 nM. INCB028050 was also effective in multiple murine models of arthritis, with no evidence of suppression of humoral immunity or adverse hematologic effects. Baricitinib was approved for the treatment of rheumatoid arthritis (RA) in the United States.

Chemical Structure

Baricitinib

CAS#1187594-09-7 (free base)

Theoretical Analysis

MedKoo Cat#: 205893

Name: Baricitinib

CAS#: 1187594-09-7 (free base)

Chemical Formula: C16H17N7O2S

Exact Mass: 371.1164

Molecular Weight: 371.42

Elemental Analysis: C, 51.74; H, 4.61; N, 26.40; O, 8.62; S, 8.63

Price and Availability

Size	Price	Availability
50mg	USD 110.00	Ready to ship
100mg	USD 180.00	Ready to ship
200mg	USD 300.00	Ready to ship
500mg	USD 650.00	Ready to ship
1g	USD 1,050.00	Ready to ship
2g	USD 1,850.00	Ready to Ship

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Related CAS #

1187594-09-7 (free base) 1187595-84-1 (phosphate)

Synonym

INCB028050; INCB-028050; INCB 028050; LY3009104; LY-3009104; LY 3009104; Baricitinib; Olumiant

IUPAC/Chemical Name

2-(3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(ethylsulfonyl)azetidin-3-yl)acetonitrile

InChi Key

XUZMWHLSFXCVMG-UHFFFAOYSA-N

InChi Code

InChI=1S/C16H17N7O2S/c1-2-26(24,25)22-9-16(10-22,4-5-17)23-8-12(7-21-23)14-13-3-6-18-15(13)20-11-19-14/h3,6-8,11H,2,4,9-10H2,1H3,(H,18,19,20)

SMILES Code

N#CCC1(N2N=CC(C3=C4C(NC=C4)=NC=N3)=C2)CN(S(=O)(CC)=O)C1

Appearance

white 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, not in water

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

Related CAS# 1187594-09-7 (Baricitinib free base) 1187595-84-1 (Baricitinib phosphate)

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#SSC50313

QC Data

View QC data: current batch, Lot#SSC50313

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Baricitinib (LY3009104; INCB028050) is a selective JAK1 and JAK2 inhibitor with IC50s of 5.9 nM and 5.7 nM, respectively.

In vitro activity:

In cell-based assays, Baricitinib (INCB028050) proves to be a potent inhibitor of JAK signaling and function. In PBMCs, Baricitinib inhibits IL-6-stimulated phosphorylation of the canonical substrate STAT3 (pSTAT3) and subsequent production of the chemokine MCP-1 with IC50 values of 44 nM and 40 nM, respectively. In isolated naive T-cells, INCB028050 also inhibits pSTAT3 stimulated by IL-23 (IC50=20 nM). Importantly, this inhibition prevented the production of two pathogenic cytokines (IL-17 and IL-22) produced by Th17 cells-a subtype of helper T cells with demonstrable inflammatory and pathogenic properties-with an IC50 value of 50 nM. In stark contrast, the structurally similar but ineffective JAK1/2 inhibitors INCB027753 and INCB029843 has no significant effect in any of these assays systems when tested at concentrations up to 10 μM Reference: J Immunol. 2010 May 1;184(9):5298-307. http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=20363976

In vivo activity:

Three sets of in vivo experiments were conducted to investigate the mechanisms of action of baricitinib for AA. C3H/HeJ grafted alopecic mice were treated with systemically administered baricitinib or vehicle/placebo control either prior to (Supplementary Fig. 2) or following the establishment of alopecia (Supplementary Fig. 3). Furthermore, C3H/HeJ grafted alopecic mice were treated with a topical formulation of baricitinib or vehicle control after the mice developed alopecia (Fig. 2). In all three cases, hair growth was consistently observed in baricitinib-treated mice, compared with no clinical evidence of hair regrowth in vehicle control treated mice (Fig. 2 and Supplementary Figs. 2 and 3). Skin biopsies were taken 12 weeks after the start of treatment and assessed for immune cell infiltration and loss of immune privilege. Baricitinib treated mice exhibited substantially reduced inflammation as assessed by H&E staining, reduced CD8 infiltration, and reduced MHC class I and class II expression when compared with vehicle-control treated mice (Fig. 2). CD8+NKG2D+ cells, critical effectors of disease in murine and human AA, were greatly diminished in baricitinib treated mice compared with vehicle control treated mice (Fig. 2). Reference: EBioMedicine. 2015 Feb 26;2(4):351-5. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/26137574/

	Solvent	mg/mL	mM
Solubility
	DMSO	74.0	199.24

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 371.42 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:

In vitro protocol:

In vivo protocol:

1. Fridman JS, Scherle PA, Collins R, Burn TC, Li Y, Li J, Covington MB, Thomas B, Collier P, Favata MF, Wen X, Shi J, McGee R, Haley PJ, Shepard S, Rodgers JD, Yeleswaram S, Hollis G, Newton RC, Metcalf B, Friedman SM, Vaddi K. Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050. J Immunol. 2010 May 1;184(9):5298-307. doi: 10.4049/jimmunol.0902819. Epub 2010 Apr 2. PMID: 20363976. 2. Jabbari A, Dai Z, Xing L, Cerise JE, Ramot Y, Berkun Y, Sanchez GA, Goldbach-Mansky R, Christiano AM, Clynes R, Zlotogorski A. Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib. EBioMedicine. 2015 Feb 26;2(4):351-5. doi: 10.1016/j.ebiom.2015.02.015. PMID: 26137574; PMCID: PMC4486197.

1: King B, Ohyama M, Kwon O, Zlotogorski A, Ko J, Mesinkovska NA, Hordinsky M, Dutronc Y, Wu WS, McCollam J, Chiasserini C, Yu G, Stanley S, Holzwarth K, DeLozier AM, Sinclair R; BRAVE-AA Investigators. Two Phase 3 Trials of Baricitinib for Alopecia Areata. N Engl J Med. 2022 May 5;386(18):1687-1699. doi: 10.1056/NEJMoa2110343. Epub 2022 Mar 26. PMID: 35334197. 2: Messenger A, Harries M. Baricitinib in Alopecia Areata. N Engl J Med. 2022 May 5;386(18):1751-1752. doi: 10.1056/NEJMe2203440. PMID: 35507486. 3: Assadiasl S, Fatahi Y, Mosharmovahed B, Mohebbi B, Nicknam MH. Baricitinib: From Rheumatoid Arthritis to COVID-19. J Clin Pharmacol. 2021 Oct;61(10):1274-1285. doi: 10.1002/jcph.1874. Epub 2021 Jun 12. PMID: 33870531; PMCID: PMC8250677. 4: Taylor PC, Keystone EC, van der Heijde D, Weinblatt ME, Del Carmen Morales L, Reyes Gonzaga J, Yakushin S, Ishii T, Emoto K, Beattie S, Arora V, Gaich C, Rooney T, Schlichting D, Macias WL, de Bono S, Tanaka Y. Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2017 Feb 16;376(7):652-662. doi: 10.1056/NEJMoa1608345. PMID: 28199814. 5: Marconi VC, Ramanan AV, de Bono S, Kartman CE, Krishnan V, Liao R, Piruzeli MLB, Goldman JD, Alatorre-Alexander J, de Cassia Pellegrini R, Estrada V, Som M, Cardoso A, Chakladar S, Crowe B, Reis P, Zhang X, Adams DH, Ely EW; COV-BARRIER Study Group. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. Lancet Respir Med. 2021 Dec;9(12):1407-1418. doi: 10.1016/S2213-2600(21)00331-3. Epub 2021 Sep 1. Erratum in: Lancet Respir Med. 2021 Oct;9(10):e102. PMID: 34480861; PMCID: PMC8409066. 6: Wan H, Jia H, Xia T, Zhang D. Comparative efficacy and safety of abrocitinib, baricitinib, and upadacitinib for moderate-to-severe atopic dermatitis: A network meta-analysis. Dermatol Ther. 2022 Sep;35(9):e15636. doi: 10.1111/dth.15636. Epub 2022 Jul 27. PMID: 35703351; PMCID: PMC9541568. 7: King B, Ko J, Forman S, Ohyama M, Mesinkovska N, Yu G, McCollam J, Gamalo M, Janes J, Edson-Heredia E, Holzwarth K, Dutronc Y. Efficacy and safety of the oral Janus kinase inhibitor baricitinib in the treatment of adults with alopecia areata: Phase 2 results from a randomized controlled study. J Am Acad Dermatol. 2021 Oct;85(4):847-853. doi: 10.1016/j.jaad.2021.05.050. Epub 2021 Jun 16. PMID: 34090959. 8: Jorgensen SCJ, Tse CLY, Burry L, Dresser LD. Baricitinib: A Review of Pharmacology, Safety, and Emerging Clinical Experience in COVID-19. Pharmacotherapy. 2020 Aug;40(8):843-856. doi: 10.1002/phar.2438. Epub 2020 Jul 27. PMID: 32542785; PMCID: PMC7323235. 9: Traves PG, Murray B, Campigotto F, Galien R, Meng A, Di Paolo JA. JAK selectivity and the implications for clinical inhibition of pharmacodynamic cytokine signalling by filgotinib, upadacitinib, tofacitinib and baricitinib. Ann Rheum Dis. 2021 Jul;80(7):865-875. doi: 10.1136/annrheumdis-2020-219012. Epub 2021 Mar 19. PMID: 33741556; PMCID: PMC8237188. 10: Reich K, Kabashima K, Peris K, Silverberg JI, Eichenfield LF, Bieber T, Kaszuba A, Kolodsick J, Yang FE, Gamalo M, Brinker DR, DeLozier AM, Janes JM, Nunes FP, Thyssen JP, Simpson EL. Efficacy and Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatol. 2020 Dec 1;156(12):1333-1343. doi: 10.1001/jamadermatol.2020.3260. PMID: 33001140; PMCID: PMC7527941. 11: Taylor PC, Takeuchi T, Burmester GR, Durez P, Smolen JS, Deberdt W, Issa M, Terres JR, Bello N, Winthrop KL. Safety of baricitinib for the treatment of rheumatoid arthritis over a median of 4.6 and up to 9.3 years of treatment: final results from long-term extension study and integrated database. Ann Rheum Dis. 2022 Mar;81(3):335-343. doi: 10.1136/annrheumdis-2021-221276. Epub 2021 Oct 27. PMID: 34706874; PMCID: PMC8862028. 12: Wallace DJ, Furie RA, Tanaka Y, Kalunian KC, Mosca M, Petri MA, Dörner T, Cardiel MH, Bruce IN, Gomez E, Carmack T, DeLozier AM, Janes JM, Linnik MD, de Bono S, Silk ME, Hoffman RW. Baricitinib for systemic lupus erythematosus: a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet. 2018 Jul 21;392(10143):222-231. doi: 10.1016/S0140-6736(18)31363-1. Erratum in: Lancet. 2018 Aug 11;392(10146):476. PMID: 30043749. 13: Hoang TN, Pino M, Boddapati AK, Viox EG, Starke CE, Upadhyay AA, Gumber S, Nekorchuk M, Busman-Sahay K, Strongin Z, Harper JL, Tharp GK, Pellegrini KL, Kirejczyk S, Zandi K, Tao S, Horton TR, Beagle EN, Mahar EA, Lee MYH, Cohen J, Jean SM, Wood JS, Connor-Stroud F, Stammen RL, Delmas OM, Wang S, Cooney KA, Sayegh MN, Wang L, Filev PD, Weiskopf D, Silvestri G, Waggoner J, Piantadosi A, Kasturi SP, Al-Shakhshir H, Ribeiro SP, Sekaly RP, Levit RD, Estes JD, Vanderford TH, Schinazi RF, Bosinger SE, Paiardini M. Baricitinib treatment resolves lower-airway macrophage inflammation and neutrophil recruitment in SARS-CoV-2-infected rhesus macaques. Cell. 2021 Jan 21;184(2):460-475.e21. doi: 10.1016/j.cell.2020.11.007. Epub 2020 Nov 10. PMID: 33278358; PMCID: PMC7654323. 14: Wolfe CR, Tomashek KM, Patterson TF, Gomez CA, Marconi VC, Jain MK, Yang OO, Paules CI, Palacios GMR, Grossberg R, Harkins MS, Mularski RA, Erdmann N, Sandkovsky U, Almasri E, Pineda JR, Dretler AW, de Castilla DL, Branche AR, Park PK, Mehta AK, Short WR, McLellan SLF, Kline S, Iovine NM, El Sahly HM, Doernberg SB, Oh MD, Huprikar N, Hohmann E, Kelley CF, Holodniy M, Kim ES, Sweeney DA, Finberg RW, Grimes KA, Maves RC, Ko ER, Engemann JJ, Taylor BS, Ponce PO, Larson L, Melendez DP, Seibert AM, Rouphael NG, Strebe J, Clark JL, Julian KG, de Leon AP, Cardoso A, de Bono S, Atmar RL, Ganesan A, Ferreira JL, Green M, Makowski M, Bonnett T, Beresnev T, Ghazaryan V, Dempsey W, Nayak SU, Dodd LE, Beigel JH, Kalil AC; ACTT-4 Study Group. Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo- controlled trial. Lancet Respir Med. 2022 Sep;10(9):888-899. doi: 10.1016/S2213-2600(22)00088-1. Epub 2022 May 23. PMID: 35617986; PMCID: PMC9126560. 15: Bieber T, Feist E, Irvine AD, Harigai M, Haladyj E, Ball S, Deberdt W, Issa M, Grond S, Taylor PC. A Review of Safety Outcomes from Clinical Trials of Baricitinib in Rheumatology, Dermatology and COVID-19. Adv Ther. 2022 Nov;39(11):4910-4960. doi: 10.1007/s12325-022-02281-4. Epub 2022 Sep 5. Erratum in: Adv Ther. 2023 Jun 22;: PMID: 36063279; PMCID: PMC9443639. 16: Melo A, Carrascosa JM, Torres T. Baricitinib for the treatment of atopic dermatitis. J Dermatolog Treat. 2022 Aug;33(5):2404-2413. doi: 10.1080/09546634.2021.1967268. Epub 2021 Aug 23. PMID: 34379541. 17: Slomski A. Oral Baricitinib Restores Hair Loss in Alopecia Areata. JAMA. 2022 Jun 28;327(24):2386. doi: 10.1001/jama.2022.10378. PMID: 35762995. 18: Wang F, Sun L, Wang S, Davis JM 3rd, Matteson EL, Murad MH, Luo F, Vassallo R. Efficacy and Safety of Tofacitinib, Baricitinib, and Upadacitinib for Rheumatoid Arthritis: A Systematic Review and Meta-Analysis. Mayo Clin Proc. 2020 Jul;95(7):1404-1419. doi: 10.1016/j.mayocp.2020.01.039. Epub 2020 Jun 1. PMID: 32499126. 19: Ely EW, Ramanan AV, Kartman CE, de Bono S, Liao R, Piruzeli MLB, Goldman JD, Saraiva JFK, Chakladar S, Marconi VC; COV-BARRIER Study Group. Efficacy and safety of baricitinib plus standard of care for the treatment of critically ill hospitalised adults with COVID-19 on invasive mechanical ventilation or extracorporeal membrane oxygenation: an exploratory, randomised, placebo- controlled trial. Lancet Respir Med. 2022 Apr;10(4):327-336. doi: 10.1016/S2213-2600(22)00006-6. Epub 2022 Feb 3. Erratum in: Lancet Respir Med. 2022 Feb 11;: PMID: 35123660; PMCID: PMC8813065. 20: Hoy SM. Baricitinib: A Review in Moderate to Severe Atopic Dermatitis. Am J Clin Dermatol. 2022 May;23(3):409-420. doi: 10.1007/s40257-022-00684-1. Epub 2022 May 3. Erratum in: Am J Clin Dermatol. 2022 Sep;23(5):747. PMID: 35503162; PMCID: PMC9061224.