Fedratinib
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MedKoo CAT#: 202893

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

Description: 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

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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: 524.26
Molecular Weight: 524.678
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 Ready to ship
25mg USD 200 Ready to ship
50mg USD 300 Ready to ship
100mg USD 500 Ready to ship
200mg USD 850 Ready to ship
500mg USD 1650 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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 126.7 241.42
Ethanol 0.5 0.95

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.

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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.