CYT387 sulfate salt

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的选择性 JAK1/JAK2 抑制剂，IC50 为 11/18 nM。

A potent and selective JAK1/JAK2 inhibitor with IC50 of 11/18 nM; shows significantly less activity against other kinases, including JAK3 (IC50=155 nM); inhibits JAK2V617F (JH1-JH2) withIC50 of 11 nM; inhibits growth of Ba/F3-JAK2V617F and HEL cells (IC50=1500 nM) or Ba/F3-MPLW515L cells (IC50=200 nM). Bone Cancer Phase 3 Clinical.

Momelotinib sulfate (CYT387 sulfate salt) inhibits growth of Ba/F3-JAK2V617F and human erythroleukemia (HEL) cells (IC50=1.5 μM) or Ba/F3-MPLW515L cells (IC50=200 nM), but has considerably less activity against BCR-ABL harboring K562 cells (IC50=58 μM) and FLT3 mutation harboring MV4-11 cells (IC50=3 μM). Proliferation of parental Ba/F3 cells (Ba/F3-wt) stimulated with IL-3 is inhibited with an IC50 value of 1.4 μM, consistent with the established role of IL-3-dependent signaling in the parental cell line.

Momelotinib sulfate (CYT387 sulfate salt) at twice the dose used in disease model (50 and 100 mg/kg) has little to no effect on peripheral blood counts over a period of 8 weeks. Median plasma peak concentrations are 7.1 μM with the lower dose and 32.1μM with the higher dose, with a half-life of approximately 2 hours. Trough levels at 12 hours are 10nM for the 25 mg/kg and 900nM for the 50 mg/kg dose. At day 34 after transplantation, the mean white blood cell counts and hematocrit values of the entire cohort exceeded the normal range for Balb/c mice by more than 1 SD. At this point, 6 mice are sacrificed and subjected to autopsy. In the remaining animals, treatment is initiated with 25 mg/kg Momelotinib sulfate (CYT387 sulfate salt), 50 mg/kg Momelotinib sulfate (CYT387 sulfate salt), or vehicle, administered twice daily by oral gavage (12 mice per treatment group). A rapid drop of the white cell counts is apparent in both dose cohorts as early as 6 days after initiation of treatment and a decline of the hematocrit is apparent after 20 days. After oral dosing, Momelotinib sulfate (CYT387 sulfate salt) exhibits high plasma concentrations (Cmax= 40.4 μM; Tmax=4 h), with quantitative absolute oral bioavailability and an apparent half life of 2.4 h. The high oral bioavailability, can likely be partly ascribed to the low blood clearance of Momelotinib sulfate (CYT387 sulfate salt) (6.3 mL/min/kg) and therefore low susceptibility to hepatic first pass metabolism.

CYT-387 sulfate | CYT 387 sulfate | Momelotinib sulfate

Angiogenesis

JAK

JAK

Cancer

Bone Cancer

1056636-06-6

610.6168

C23H26N6O10S2

>98% (HPLC)

DMSO: ≥ 6.1 mg/mL

C1COCCN1C2=CC=C(C=C2)NC3=NC=CC(=N3)C4=CC=C(C=C4)C(=O)NCC#N.OS(=O)(=O)O.OS(=O)(=O)O

Benzamide, N-(cyanomethyl)-4-[2-[[4-(4-morpholinyl)phenyl]amino]-4-pyrimidinyl]-, sulfate (1:2)

(-20℃)

With Ice Pack

≥ 2 years