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MedKoo Cat#: 202893 | Name: Fedratinib
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Description:

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

Fedratinib, also known as TG101348 and SAR302503, is a JAK2 inhibitor, is also an orally bioavailable, small-molecule, ATP-competitive inhibitor of Janus-associated kinase 2 (JAK2) with potential antineoplastic activity. JAK2 inhibitor TG101348 competes with JAK2 as well as the mutated form AK2V617F for ATP binding, which may result in inhibition of JAK2 activation, inhibition of the JAK-STAT signaling pathway, and the induction of tumor cell apoptosis. JAK2 is the most common mutated gene in bcr-abl-negative myeloproliferative disorders (MPDs); the mutated form JAK2V617F has a valine-to-phenylalanine modification at position 617 and plays a key role in tumor cell proliferation and survival.

Chemical Structure

Fedratinib
Fedratinib
CAS#936091-26-8 (free base)

Theoretical Analysis

MedKoo Cat#: 202893

Name: Fedratinib

CAS#: 936091-26-8 (free base)

Chemical Formula: C27H36N6O3S

Exact Mass: 524.2570

Molecular Weight: 524.68

Elemental Analysis: C, 61.81; H, 6.92; N, 16.02; O, 9.15; S, 6.11

Price and Availability

Size Price Availability Quantity
10mg USD 90.00 Ready to ship
25mg USD 200.00 Ready to ship
50mg USD 300.00 Ready to ship
100mg USD 500.00 Ready to ship
200mg USD 850.00 Ready to ship
500mg USD 1,650.00 Ready to ship
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Related CAS #
936091-26-8 (free base) 1374744-69-0 (HCl hydrate) 2468204-70-6 (HCl)
Synonym
TG101348; TG 101348; TG-101348; SAR302503; SAR-302503; SAR 302503; Fedratinib.
IUPAC/Chemical Name
N-(tert-butyl)-3-((5-methyl-2-((4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)amino)pyrimidin-4-yl)amino)benzenesulfonamide
InChi Key
JOOXLOJCABQBSG-UHFFFAOYSA-N
InChi Code
InChI=1S/C27H36N6O3S/c1-20-19-28-26(30-21-10-12-23(13-11-21)36-17-16-33-14-5-6-15-33)31-25(20)29-22-8-7-9-24(18-22)37(34,35)32-27(2,3)4/h7-13,18-19,32H,5-6,14-17H2,1-4H3,(H2,28,29,30,31)
SMILES Code
O=S(C1=CC=CC(NC2=NC(NC3=CC=C(OCCN4CCCC4)C=C3)=NC=C2C)=C1)(NC(C)(C)C)=O
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 (45mg/mL)
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
 
Biological target:
Fedratinib (TG-101348) is an ATP-competitive JAK2 inhibitor with IC50s of 3 nM for both JAK2 and JAK2V617F kinase.
In vitro activity:
Fedratinib-treated hMSC-TERT cells (3 µM) exhibited a significant reduction in ALP production, as evidenced by reduced cytochemical staining intensity (Figure 2B) compared with DMSO-vehicle treated control cells (Figure 2A). Moreover, the measurement of ALP activity at day 10 post-osteoblast differentiation induction was reduced compared with DMSO-vehicle treated control cells (Figure 2C). Fedratinib did not exert significant effects on hMSC-TERT cells viability at day 10 post-osteoblast differentiation induction (Figure 2D). Fedratinib-treated hMSC-TERT cells (3 µM) exhibited a significant decrease in mineralised matrix formation, as demonstrated by Alizarin red staining (Figure 3B), compared with DMSO-vehicle treated control cells (Figure 3A), which was associated with the significant downregulation of several osteoblast gene markers: ALP, ON, OC, RUNX2, OPN, and COL1A1 (Figure 4B). Reference: Molecules. 2021 Feb; 26(3): 606. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866227/
In vivo activity:
These studies demonstrate that TG101348 decreases atherosclerosis in Apoe−/− mice, likely by selective inhibition of hematopoietic JAK2 that results in suppression of excessive myelopoiesis driven by enhanced cell proliferation signaling in HSPCs and myeloid progenitors and reversal of HSPC expansion and leukocytosis. This suggests the possible translation of TG101348 therapy in reducing the risk of ACD in association with moderate myeloproliferation with or without JAK2 mutations. Reference: Cardiovasc Drugs Ther. 2020; 34(2): 145–152. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125070/
Solvent mg/mL mM
Solubility
DMSO 126.7 241.42
Ethanol 0.5 0.95
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 524.68 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. AlMuraikhi N, Alaskar H, Binhamdan S, Alotaibi A, Kassem M, Alfayez M. JAK2 Inhibition by Fedratinib Reduces Osteoblast Differentiation and Mineralisation of Human Mesenchymal Stem Cells. Molecules. 2021 Jan 25;26(3):606. doi: 10.3390/molecules26030606. PMID: 33503825; PMCID: PMC7866227. 2. Pitroda SP, Stack ME, Liu GF, Song SS, Chen L, Liang H, Parekh AD, Huang X, Roach P, Posner MC, Weichselbaum RR, Khodarev NN. JAK2 Inhibitor SAR302503 Abrogates PD-L1 Expression and Targets Therapy-Resistant Non-small Cell Lung Cancers. Mol Cancer Ther. 2018 Apr;17(4):732-739. doi: 10.1158/1535-7163.MCT-17-0667. Epub 2018 Feb 21. PMID: 29467274. 3. Tang Y, Liu W, Wang W, Fidler T, Woods B, Levine RL, Tall AR, Wang N. Inhibition of JAK2 Suppresses Myelopoiesis and Atherosclerosis in Apoe-/- Mice. Cardiovasc Drugs Ther. 2020 Apr;34(2):145-152. doi: 10.1007/s10557-020-06943-9. PMID: 32086626; PMCID: PMC7125070. 4. Zhang L, Wang Y, Wu G, Rao L, Wei Y, Yue H, Yuan T, Yang P, Xiong F, Zhang S, Zhou Q, Chen Z, Li J, Mo BW, Zhang H, Xiong W, Wang CY. Blockade of JAK2 protects mice against hypoxia-induced pulmonary arterial hypertension by repressing pulmonary arterial smooth muscle cell proliferation. Cell Prolif. 2020 Feb;53(2):e12742. doi: 10.1111/cpr.12742. Epub 2020 Jan 14. PMID: 31943454; PMCID: PMC7046303.
In vitro protocol:
1. AlMuraikhi N, Alaskar H, Binhamdan S, Alotaibi A, Kassem M, Alfayez M. JAK2 Inhibition by Fedratinib Reduces Osteoblast Differentiation and Mineralisation of Human Mesenchymal Stem Cells. Molecules. 2021 Jan 25;26(3):606. doi: 10.3390/molecules26030606. PMID: 33503825; PMCID: PMC7866227. 2. Pitroda SP, Stack ME, Liu GF, Song SS, Chen L, Liang H, Parekh AD, Huang X, Roach P, Posner MC, Weichselbaum RR, Khodarev NN. JAK2 Inhibitor SAR302503 Abrogates PD-L1 Expression and Targets Therapy-Resistant Non-small Cell Lung Cancers. Mol Cancer Ther. 2018 Apr;17(4):732-739. doi: 10.1158/1535-7163.MCT-17-0667. Epub 2018 Feb 21. PMID: 29467274.
In vivo protocol:
1. Tang Y, Liu W, Wang W, Fidler T, Woods B, Levine RL, Tall AR, Wang N. Inhibition of JAK2 Suppresses Myelopoiesis and Atherosclerosis in Apoe-/- Mice. Cardiovasc Drugs Ther. 2020 Apr;34(2):145-152. doi: 10.1007/s10557-020-06943-9. PMID: 32086626; PMCID: PMC7125070. 2. Zhang L, Wang Y, Wu G, Rao L, Wei Y, Yue H, Yuan T, Yang P, Xiong F, Zhang S, Zhou Q, Chen Z, Li J, Mo BW, Zhang H, Xiong W, Wang CY. Blockade of JAK2 protects mice against hypoxia-induced pulmonary arterial hypertension by repressing pulmonary arterial smooth muscle cell proliferation. Cell Prolif. 2020 Feb;53(2):e12742. doi: 10.1111/cpr.12742. Epub 2020 Jan 14. PMID: 31943454; PMCID: PMC7046303.
1: Smullen S, McLaughlin NP, Evans P. Chemical synthesis of febrifugine and analogues. Bioorg Med Chem. 2018 May 15;26(9):2199-2220. doi: 10.1016/j.bmc.2018.04.027. Epub 2018 Apr 12. PMID: 29681487. 2: McLaughlin NP, Evans P, Pines M. The chemistry and biology of febrifugine and halofuginone. Bioorg Med Chem. 2014 Apr 1;22(7):1993-2004. doi: 10.1016/j.bmc.2014.02.040. Epub 2014 Mar 1. PMID: 24650700. 3: Mitsui Y, Miura M, Kato K. In vitro effects of febrifugine on Schistosoma mansoni adult worms. Trop Med Health. 2020 Jun 4;48:42. doi: 10.1186/s41182-020-00230-x. PMID: 32518498; PMCID: PMC7271449. 4: Pandey RK, Ojha R, Devender M, Sebastian P, Namdeo M, Kumbhar BV, Sundar S, Maurya R, Prajapati VK. Febrifugine dihydrochloride as a new oral chemotherapeutic agent against visceral leishmaniasis infection. Exp Parasitol. 2022 May-Jun;236-237:108250. doi: 10.1016/j.exppara.2022.108250. Epub 2022 Apr 4. PMID: 35390313. 5: Zhu S, Chandrashekar G, Meng L, Robinson K, Chatterji D. Febrifugine analogue compounds: synthesis and antimalarial evaluation. Bioorg Med Chem. 2012 Jan 15;20(2):927-32. doi: 10.1016/j.bmc.2011.11.053. Epub 2011 Dec 2. PMID: 22182577; PMCID: PMC3259200. 6: Zhang JY, Liu XQ, Yang LX, Feng WH, Wang ZM, Li C. [Investigation on stability and degradation kinetics of febrifugine]. Zhongguo Zhong Yao Za Zhi. 2017 Aug;42(16):3178-3184. Chinese. doi: 10.19540/j.cnki.cjcmm.2017.0126. PMID: 29171238. 7: Murata K, Takano F, Fushiya S, Oshima Y. Potentiation by febrifugine of host defense in mice against Plasmodium berghei NK65. Biochem Pharmacol. 1999 Nov 15;58(10):1593-601. doi: 10.1016/s0006-2952(99)00244-0. PMID: 10535750. 8: Maiden TMM, Mbelesi N, Procopiou PA, Swanson S, Harrity JPA. A convergent strategy towards febrifugine and related compounds. Org Biomol Chem. 2018 Jun 6;16(22):4159-4169. doi: 10.1039/c8ob00935j. PMID: 29786725. 9: Autreto PA, Lavarda FC. Febrifugine derivative antimalarial activity: quantum mechanical predictors. Rev Inst Med Trop Sao Paulo. 2008 Jan-Feb;50(1):21-4. doi: 10.1590/s0036-46652008000100005. PMID: 18327483. 10: Jiang S, Zeng Q, Gettayacamin M, Tungtaeng A, Wannaying S, Lim A, Hansukjariya P, Okunji CO, Zhu S, Fang D. Antimalarial activities and therapeutic properties of febrifugine analogs. Antimicrob Agents Chemother. 2005 Mar;49(3):1169-76. doi: 10.1128/AAC.49.3.1169-1176.2005. PMID: 15728920; PMCID: PMC549280. 11: Zhang JY, Fan XR, Liu XQ, Yu XW, Yang LX, Guo ZT, Feng WH, Wang ZM, Li C. [Quantitative determination of febrifugine by proton nuclear magnetic resonance spectroscopy with internal standard method]. Zhongguo Zhong Yao Za Zhi. 2018 Jan;43(1):134-138. Chinese. doi: 10.19540/j.cnki.cjcmm.20171027.005. PMID: 29552823. 12: Wang F, Zhang G, Zang C, Pan H, Ma L, Li C, Hou H, Su P, Gao Y, Sun J, Ye Z. Preparation and In Vitro/Vivo Evaluation of Nano-Liposomal Form of Febrifugine Hydrochloride. J Nanosci Nanotechnol. 2020 Apr 1;20(4):2558-2566. doi: 10.1166/jnn.2020.17186. PMID: 31492276. 13: Cheng CC. Structural similarity between febrifugine and chloroquine. J Theor Biol. 1976 Jul 7;59(2):497-501. doi: 10.1016/0022-5193(76)90186-7. PMID: 957703. 14: Li PP, Zhang L, Wang JP. Research Note: Study on the residue depletion of febrifugine and isofebrifugine in broiler chicken. Poult Sci. 2021 Oct;100(10):101390. doi: 10.1016/j.psj.2021.101390. Epub 2021 Jul 22. PMID: 34391965; PMCID: PMC8374448. 15: Zhu S, Meng L, Zhang Q, Wei L. Synthesis and evaluation of febrifugine analogues as potential antimalarial agents. Bioorg Med Chem Lett. 2006 Apr 1;16(7):1854-8. doi: 10.1016/j.bmcl.2006.01.009. Epub 2006 Jan 24. PMID: 16434194; PMCID: PMC2072810. 16: Zhang JY, Liu ZH, Liu XQ, Feng WH, Yang LX, Wang ZM, Li C. [Simultaneous determination of febrifugine and isofebrifugine in Dichroa febrifuga root by HPLC method]. Zhongguo Zhong Yao Za Zhi. 2017 May;42(9):1711-1716. Chinese. doi: 10.19540/j.cnki.cjcmm.20170224.017. PMID: 29082694. 17: Takeuchi Y, Oshige M, Azuma K, Abe H, Harayama T. Concise synthesis of dl- febrifugine. Chem Pharm Bull (Tokyo). 2005 Jul;53(7):868-9. doi: 10.1248/cpb.53.868. PMID: 15997158. 18: Kikuchi H, Tasaka H, Hirai S, Takaya Y, Iwabuchi Y, Ooi H, Hatakeyama S, Kim HS, Wataya Y, Oshima Y. Potent antimalarial febrifugine analogues against the plasmodium malaria parasite. J Med Chem. 2002 Jun 6;45(12):2563-70. doi: 10.1021/jm010448q. PMID: 12036365. 19: Zhu S, Zhang Q, Gudise C, Wei L, Smith E, Zeng Y. Synthesis and biological evaluation of febrifugine analogues as potential antimalarial agents. Bioorg Med Chem. 2009 Jul 1;17(13):4496-502. doi: 10.1016/j.bmc.2009.05.011. Epub 2009 May 9. PMID: 19467876; PMCID: PMC2746662. 20: Pandey RK, Kumbhar BV, Srivastava S, Malik R, Sundar S, Kunwar A, Prajapati VK. Febrifugine analogues as Leishmania donovani trypanothione reductase inhibitors: binding energy analysis assisted by molecular docking, ADMET and molecular dynamics simulation. J Biomol Struct Dyn. 2017 Jan;35(1):141-158. doi: 10.1080/07391102.2015.1135298. Epub 2016 Apr 4. PMID: 27043972.
1. Dai Z, Chen J, Chang Y, Christiano AM. Selective inhibition of JAK3 signaling is sufficient to reverse alopecia areata. JCI Insight. 2021 Apr 8;6(7):142205. doi: 10.1172/jci.insight.142205. PMID: 33830087.