1056634-68-4 CYT387 AKSci J98835
 
 
Loading Please Wait...
  J98835    
CYT387
, 95%
 
N-(Cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide

Structure N/A

IDENTITY
CAS Number:1056634-68-4
MDL Number:MFCD16038899
MF:C23H22N6O2
MW:414.46
SPECIFICATIONS & PROPERTIES
Purity:95%
Physical Form:Yellow powder
Melting Point:240-245°C
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 July 6, 2020


Download SDS

For research use only. Not for diagnostic or therapeutic use. Not for human use. AK Scientific, Inc. does not sell to individuals. If you are a first-time customer, please email for review at least two official business documents issued by your local jurisdiction, state/province, or country.


CATEGORIES

 APIs and Bioactives > Protein kinase inhibitors


PubChem