935666-88-9 Usage
Description
5-Chloro-N2-[(1S)-1-(5-fluoro-2-pyrimidinyl)ethyl]-N4-(5-methyl-1H-pyrazol-3-yl)-2,4-pyrimidinediamine, also known as AZD1480, is a small molecule compound with a complex chemical structure. It is characterized by the presence of a chloro group, a 5-fluoro-2-pyrimidinylethyl group, and a 5-methyl-1H-pyrazol-3-yl group attached to a 2,4-pyrimidinediamine core. 5-Chloro-N2-[(1S)-1-(5-fluoro-2-pyrimidinyl)ethyl]-N4-(5-methyl-1H-pyrazol-3-yl)-2,4-pyrimidinediamine has been studied for its potential therapeutic applications in various fields.
Uses
Used in Oncology Research:
5-Chloro-N2-[(1S)-1-(5-fluoro-2-pyrimidinyl)ethyl]-N4-(5-methyl-1H-pyrazol-3-yl)-2,4-pyrimidinediamine is used as an inhibitor of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) for studying the role of these proteins in upper gastrointestinal adenocarcinoma. Its ability to target these proteins makes it a valuable tool in understanding the molecular mechanisms underlying cancer development and progression.
Used in Combination Therapy Studies:
In addition to its standalone use, 5-Chloro-N2-[(1S)-1-(5-fluoro-2-pyrimidinyl)ethyl]-N4-(5-methyl-1H-pyrazol-3-yl)-2,4-pyrimidinediamine has been used in combination with other drugs, such as bortezomib, to investigate the effects on tumor-associated macrophage-mediated survival of myeloma cells. This research aims to explore the potential synergistic effects of combining different therapeutic agents to enhance the treatment of cancer.
Used in Pharmaceutical Industry:
5-Chloro-N2-[(1S)-1-(5-fluoro-2-pyrimidinyl)ethyl]-N4-(5-methyl-1H-pyrazol-3-yl)-2,4-pyrimidinediamine is used as a lead compound in the development of new drugs targeting JAK2 and STAT3 pathways. Its unique chemical structure and biological activity make it a promising candidate for further optimization and development into potential therapeutic agents for various cancers.
Biological Activity
azd1480 is a novel small-molecule jak inhibitor. it is able to block cell proliferation and induce apoptosis of myeloma cell lines. it can effectively inhibit tumor angiogenesis and metastasis mediated by stat3 in stromal cells as well as tumor cells. azd1480 has broad efficacy on a wider variety of myeloma cells, such as rpmi 8226, opm-2, nci-h929, kms.18, mm1.s and im-9, as well as primary myeloma cells. azd1480 induces cell death of kms.11 cells grown in the presence of hs-5 bone marrow (bm)-derived stromal cells and inhibits tumor growth in a kms.11 xenograft mouse model, accompanied with inhibition of phospho-fgfr3, phospho-jak2, phospho-stat3 and cyclin d2 levels. azd1480 also demonstrates important jak2 selectivity over jak3, in particular at high atp concentrations and marginal selectivity over jak1 at km atp.a scuto, p krejci, l popplewell, j wu, y wang, m kujawski, c kowolik, h xin, l chen, y wang, l kretzner, h yu, w r wilcox, y yen, s forman and r jove. the novel jak inhibitor azd1480 blocks stat3 and fgfr3 signaling, resulting in suppression of human myeloma cell growth and survival. leukemia. 2011 march ; 25(3): 538–550michael hedvat, dennis huszar, andreas herrmann, joseph m. gozgit, anne schroeder, adam sheehy, ralf buettner, david proia, claudia m. kowolik, hong xin, brian armstrong, geraldine bebernitz, shaobu weng, lin wang, minwei ye, kristen mceachern, huawei chen, deborah morosini, kirsten bell, marat alimzhanov, stephanos ioannidis, patricia mccoon, zhu a. cao, hua yu, richard jove, michael zinda. the jak2 inhibitor azd1480 potently blocks stat3 signaling and oncogenesis in solid tumors. cancer cell. 2009; 16 (6): 487–497hong xin, andreas herrmann, karen reckamp, wang zhang, sumanta pal, michael hedvat, chunyan zhang, wei liang, anna scuto, shaobu weng, deborah morosini, zhu a. cao, michael zinda, robert figlin, dennis huszar, richard jove, hua yu. antiangiogenic and antimetastatic activity of jak inhibitor azd1480. cancer research. 2011;71: 6601-6610
Biochem/physiol Actions
AZD1480 is an orally active, potent and selective inhibitor of Janus kinases JAK1 and JAK 2 with selectivity for JAK2 as evidenced by IC50 values of 1.3 nM for JAK1 and <0.4 nM for JAK2 in enzyme assays. AZD1480 inhibits endogenous as well as IL-6 induced STAT3 activation. AZD1480 reduces myeloid cell-mediated angiogenesis and metastasis. AZD1489 is an effective anticancer agent in bot adult and pediatric human tumors.
Check Digit Verification of cas no
The CAS Registry Mumber 935666-88-9 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 9,3,5,6,6 and 6 respectively; the second part has 2 digits, 8 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 935666-88:
(8*9)+(7*3)+(6*5)+(5*6)+(4*6)+(3*6)+(2*8)+(1*8)=219
219 % 10 = 9
So 935666-88-9 is a valid CAS Registry Number.
935666-88-9Relevant articles and documents
Use of ω-transaminase enzyme chemistry in the synthesis of a JAK2 kinase inhibitor
Frodsham, Lianne,Golden, Michael,Hard, Susan,Kenworthy, Martin N.,Klauber, David J.,Leslie, Kevin,Macleod, Claire,Meadows, Rebecca E.,Mulholland, Keith R.,Reilly, Julie,Squire, Christopher,Tomasi, Simone,Watt, Denise,Wells, Andrew S.
, p. 1123 - 1130 (2013/10/08)
ω-Transaminase enzyme chemistry provides an excellent methodology to build synthetically useful chiral amines from their corresponding ketones. An application of this methodology, providing a long-term commercial manufacturing route to a JAK2 kinase inhibitor, is reported herein.
4- (3-AMINOPYRAZOLE) PYRIMIDINE DERIVATIVES FOR USE AS TYROSINE KINASE INHIBITORS IN THE TREATMENT OF CANCER
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Page/Page column 43, (2010/11/27)
This invention relates to novel compounds having the formula (I) and to their pharmaceutical compositions and to their methods of use. These novel compounds provide a treatment for cancer.
