1056634-68-4 Usage
Description
Momelotinib, also known as CYT387, is an ATP-competitive inhibitor of Janus kinase 1 (JAK1) and Janus kinase 2 (JAK2) with IC50 values of 11 nM and 18 nM, respectively. It exhibits approximately 10-fold selectivity over JAK3. Momelotinib is currently in Phase 3 of development.
Uses
Used in Hematology Applications:
Momelotinib is used as a therapeutic agent for hematological disorders, as dysregulation of the JAK-STAT pathway is often associated with these conditions. By inhibiting JAK1 and JAK2, Momelotinib can help regulate the pathway and potentially improve patient outcomes.
Used in Oncology Applications:
Momelotinib is used as an oncology treatment, targeting the JAK-STAT pathway, which is involved in the development and progression of various cancers. Inhibiting JAK1 and JAK2 with Momelotinib may help control tumor growth and improve treatment outcomes for cancer patients.
Used in Inflammatory Disease Applications:
Momelotinib is used as an anti-inflammatory agent, as the JAK-STAT pathway is also implicated in inflammatory diseases. By inhibiting the JAK1 and JAK2 kinases, Momelotinib may help reduce inflammation and alleviate symptoms associated with these conditions.
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.
Biological Activity
cyt387, an aminopyrimidine derivative discovered by high-throughput enzyme and cell-based screening along with the optimization using structure-guided medicinal chemistry, is a potent and selective inhibitor of janus kinase 1 (jak1), janus kinase 2 (jak2) and tyrosine kinase 2 (tyk2) with values of 50% inhibition concentration ic50 of 11 nm, 18 nm, 155 nm and 17 nm respectively. recent studies have revealed that cyt387, at low nanomolar concentrations ranging between 500 and 1500 nm, is able to inhibit jak2 signaling pathway, suppress proliferation and induce apoptosis in jak2-dependent hematopoietic cell lines with non-hematopoietic cell lines intact.tyner jw, bumm tg, deininger j, wood l, aichberger kj, loriaux mm, druker bj, burns cj, fantino e, deininger mw. cyt387, a novel jak2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms. blood. 2010;115(25):5232-5240.
Check Digit Verification of cas no
The CAS Registry Mumber 1056634-68-4 includes 10 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 7 digits, 1,0,5,6,6,3 and 4 respectively; the second part has 2 digits, 6 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 1056634-68:
(9*1)+(8*0)+(7*5)+(6*6)+(5*6)+(4*3)+(3*4)+(2*6)+(1*8)=154
154 % 10 = 4
So 1056634-68-4 is a valid CAS Registry Number.
1056634-68-4Relevant articles and documents
New and Practical Synthesis of Momelotinib
Zhu, Chunping,Xue, Xue,Han, Guanyu,Mao, Yongjun,Xu, Jingli
, p. 2902 - 2905 (2017)
New and practical synthetic route of momelotinib, a JAK inhibitor, is described on a decagram scale. A convergent synthetic process is adopted to prepare the methyl 4-(2-((4-morpholinophenyl)amino)pyrimidin-4-yl) benzoate intermediate, by cyclization of 1-(4-morpholinophenyl)guanidine and methyl 4-(3-(dimethylamino)acryloyl)benzoate in high yield and mild conditions. Momelotinib is obtained in 43.2% yield over five steps and 99.1% purity (HPLC).
A novel and efficient synthesis of momelotinib
Sun, Tong,Xu, Jiaojiao,Ji, Min,Wang, Peng
, p. 511 - 513 (2016)
An improved route for the synthesis of momelotinib has been developed. A nucleophilic addition reaction between the starting material, 4-morpholinoaniline, and cyanamide gave the 1-(4-morpholinophenyl)guanidine. Simultaneously, methyl 4-acetylbenzoate was converted into methyl (E)-4-[3-(dimethylamino)acryloyl]benzoate in the presence of N,N-dimethylformamide dimethylacetal. The enaminone intermediate was then condensed at elevated temperature in alcoholic alkali with the 1-(morpholinophenyl)guanidine to form the desired pyrimidine, which was hydrolysed to the corresponding acid. This procedure is simple in operation, without noble metal catalyst and suitable for industrial production. Finally, the desired compound momelotinib was acquired by an amidation reaction.
Preparation method of JAK inhibitor momelotinib
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Paragraph 0041; 0068-0079, (2020/05/14)
The invention relates to a preparation method of a JAK inhibitor momelotinib. The preparation method provided by the invention has the advantages of simple preparation route, mild preparation conditions, cheap and easily available raw materials and relatively low synthesis cost.
