1056634-68-4 CYT387 AKSci X7506
 
 
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  X7506    
CYT387
, 98% (HPLC), powder
 
N-(Cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide




IDENTITY
CAS Number:1056634-68-4
MDL Number:MFCD16038899
MF:C23H22N6O2
MW:414.46
SPECIFICATIONS & PROPERTIES
Purity:98% (HPLC), powder
Spectra:NMR, LCMS, HPLC
Physical Form:Yellow powder
Melting Point:240-245°C
Density:1.3
Refractive Index:1.64
Long-Term Storage:Store long-term at -20°C

BIOLOGICAL INFO
Solubility:DMSO =80mg/mL Water <1.2mg/mL Ethanol <1.2mg/mL
Application(s):JAK
Form:Free Base
Research Area:myeloproliferative disorders

REVIEW

 CYT387(momelotinib) is an ATP-competitive inhibitor of JAK1/JAK2 with IC50 of 11 nM/18 nM, ~10-fold selectivity versus JAK3. IC50 value: 11 nM/18 nM(JAK1/JAK2). Target: JAK1/JAK2 in vitro: CYT387 inhibits the proliferation of parental Ba/F3 cells (Ba/F3-wt) stimulated by IL-3 with IC50 of 1400 nM. Furthermore, CYT387 also causes the inhibition of cell proliferation in cell lines constitutively activated by JAK2 or MPL signaling, including Ba/F3-MPLW515L cells, CHRF-288-11 cells and Ba/F3-TEL-JAK2 cells with IC50 of 200 nM, 1 nM and 700 nM, respectively. In addition, CYT387 has been shown to inhibit erythroid colony growth in vitro from JAK2V617F-positive PV patients with similar potency with IC50 of 2µ-4 µM. A recent study shows that CYT387 inhibits PI3K/AKT and Ras/MAPK signaling induced by IL-6 and IGF-1. Moreover, CYT387 induces apoptosis as a single agent and synergizes with the conventional anti-MM therapies bortezomib and melphalan in primary multiple myeloma (MM) cells. in vivo: In a murine MPN model, CYT387 normalizes white cell counts, hematocrit, spleen size, and restores physiologic levels of inflammatory cytokines.

REFERENCES
[1]Tyner JW, et al. CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms. Blood, 2010, 115(25), 5232-5240.
[2] Monaghan KA, et al. The novel JAK inhibitor CYT387 suppresses multiple signalling pathways, prevents proliferation and induces apoptosis in phenotypically diverse myeloma cells. Leukemia, 2011, 25(12), 1891-1899.
[3] Pardanani A, et al. CYT387, a selective JAK1/JAK2 inhibitor: in vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients. Leukemia, 2009, 23(8), 1441-1445.

GHS

Pictograms

Signal Word
Warning

Hazard Statements
H315; H319; H335

Precautionary Statements
P261; P264; P271; P280; P302+P352; P304+P340; P305+P351+P338; P312; P321; P332+P313; P337+P313; P362; P403+P233; P405; P501


Current as of October 17, 2019


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For research use only. Not for diagnostic or therapeutic use.
Not for human use.


CATEGORIES

 APIs and Bioactives > Protein kinase inhibitors


PubChem