936091-26-8 Usage
Description
Fedratinib (SAR302503, TG101348) is a selective inhibitor of JAK2 with IC50 of 3 nM in cell-free assays, 35-and 334-fold more selective for JAK2 versus JAK1 and JAK3. Phase 2.
In vitro
TG-101348 also significantly inhibits JAK2 V617F, Flt3, and Ret with IC50 of 3 nM, 15 nM, and 48 nM, respectively. TG101348 has an IC50 ~300-fold higher for the closely related JAK3 and is a less potent inhibitor of the JAK1 and TYK2 family members. TG101348 inhibits proliferation of a human erythroblast leukemia (HEL) cell line that harbors the JAK2V617F mutation, as well as a murine pro-B cell line expressing human JAK2V617F (Ba/F3 JAK2V617F), with IC50 of 305 nM and 270 nM, respectively. TG-101348 also inhibits proliferation of parental Ba/F3 cells to a comparable level, with IC50 of ~420 nM. TG101348 treatment reduces STAT5 phosphorylation at concentrations that parallel the concentrations required to inhibit cell proliferation. TG101348 induces apoptosis in both HEL and Ba/F3 JAK2V617F cells in a dose-dependent manner. TG101348 does not show proapoptotic activity in control normal human dermal fibroblasts at concentrations up to 10 μM, and the antiproliferative IC50 against fibroblasts is >5 μM. TG101348 treatment decreases GATA-1 expression, which is associated with erythroid-skewing of JAK2V617F+ progenitor differentiation, and inhibits STAT5 as well as GATA S310 phosphorylation. TG101348 inhibits the proliferation of HMC-1.1 (KITV560G) cells, with somewhat lower potency than HMC-1.2 (KITD816V, KITV560G) cells, with IC50 of 740 nM and 407 nM, respectively.
In vivo
TG101348 has potential for efficacious treatment of JAK2V617F-associated myeloproliferative diseases (MPD). In treated animals, there is a statistically significant reduction in hematocrit and leukocyte count, a dose-dependent reduction/elimination of extramedullary hematopoiesis, and, at least in some instances, evidence for attenuation of myelofibrosis, correlated with surrogate endpoints, including reduction/elimination of JAK2V617F disease burden, suppression of endogenous erythroid colony formation, and in vivo inhibition of JAK-STAT signal transduction. There are no apparent toxicities and no effect on T cell number. Oral administration of TG101348 (120 mg/kg) significantly inhibits PV progenitor erythroid differentiation in vivo.
Uses
TG101348 is a selective inhibitor of JAK2 tyrosine kinase. Potent JAK2 inhibitor.
Biological Activity
tg101348, also known as sar302503, is a potent and selective inhibitor of janus kinase 2 (jak2), one member of a family of 4 cytoplasmic tyrosine kinases including janus kinase 1(jak1), jak2, janus kinase 3 (jak3) and tyrosine kinase 2 (tyk2), with the inhibition constant ic50 of 3 nm. comparing to other close related kinases, the selectivity of tg101348 for jak2 is 35- and 334-fold stronger than that for jak3 and jak1 respectively. tg10348 is capable of inducing apoptosis in hel cells as well baf/3 cells harboring jak2v617 mutation and inhibiting hematopoietic progenitor colony formation and erythroid engraftment in samples from polycythemia vera (pv) patients.srdan verstovsek. therapeutic potential of jak2 inhibitors. hematology am soc hematol educ program 2009:636-642
Check Digit Verification of cas no
The CAS Registry Mumber 936091-26-8 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 9,3,6,0,9 and 1 respectively; the second part has 2 digits, 2 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 936091-26:
(8*9)+(7*3)+(6*6)+(5*0)+(4*9)+(3*1)+(2*2)+(1*6)=178
178 % 10 = 8
So 936091-26-8 is a valid CAS Registry Number.
936091-26-8Relevant articles and documents
Sustainable synthesis of potential antitumor new derivatives of Abemaciclib and Fedratinib via C-N cross coupling reactions using Pd/Cu-free Co-catalyst
Khorsandi, Zahra,Keshavarzipour, Fariba,Varma, Rajender S.,Hajipour, Abdol R.,Sadeghi-Aliabadi, Hojjat
, (2021/11/24)
Herein, chitosan as an inexpensive, abundant, and biodegradable bio-material, produced from a key constituent of the exoskeletons of crustaceans, was used to generate the cobalt-based magnetic silica nanocomposite for the performance of the C-N cross-coupling reaction as the main step of the synthesis of Abemaciclib and Fedratinibs. Several derivatives of these recently FDA-approved anti-cancer drugs were synthesized for the first time by using Pd/Cu-free co-catalyzed under both, the conventional heating and microwave (MW) irradiation conditions. The potential anticancer activity of synthesized compounds was investigated by molecular docking study.
A Pd/Cu-Free magnetic cobalt catalyst for C-N cross coupling reactions: synthesis of abemaciclib and fedratinib
Hajipour, Abdol R.,Khorsandi, Zahra,Sarfjoo, Mohamad Reza,Varma, Rajender S.
, p. 5222 - 5229 (2021/07/29)
Herein, the synthesis of a nano-catalytic system comprising magnetic nanoparticles as the core and edible natural ligands bearing functional groups as supports for cobalt species is described. Subsequent to its characterization, the efficiency of the catalyst was investigated for C-N cross-coupling reactions using assorted derivatives of amines and aryl halides. This novel and easily accessible Pd- and Cu-free catalyst exhibited good catalytic activity in these reactions using γ-valerolactone (GVL) at room temperature; good recyclability bodes well for the future application of this strategy. The introduced catalytic system is attractive in view of the excellent efficiency in an array of coupling reactions and its versatility is illustrated in the synthesis of abemaciclib and fedratinib, which are FDA-approved new and significant anti-cancer medicinal compounds that are prepared under green reaction conditions.
COMPOSITIONS AND METHODS FOR TREATING MYELOFIBROSIS
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, (2012/05/20)
Provided herein are compositions and methods for treating myelofibrosis in a subject. The methods comprise administering to the subject an effective amount of compound which is which is N-tert-butyl-3-[(5-methyl-2-{[4-(2-pyrrolidin-1-ylethoxy)phenyl] amin
