Basic information Safety Supplier Related
ChemicalBook >  Product Catalog >  Pharmaceutical intermediates >  Heterocyclic compound >  Pyridine compound >  Hydroxypyridine >  AS703026

AS703026

Basic information Safety Supplier Related

AS703026 Basic information

Product Name:
AS703026
Synonyms:
  • AS703026
  • 100330
  • CS-2173
  • CS-397
  • PIMASERTIB; MSC1936369B; AS-703026; AS 703026; PIMASERTIB; MSC1936369B; AS-703026; AS 703026
  • MSC1936369B;PIMASERTIB
  • N-[(2S)-2,3-Dihydroxypropyl]-3-[(2-fluoro-4-iodophenyl)amino]-4-pyridinecarboxamide
  • (S)-N-(2,3-dihydroxypropyl)-3-(2-fluoro-4-iodophenylaMino)isonicotinaMide
CAS:
1236699-92-5
MF:
C15H15FIN3O3
MW:
431.2
Product Categories:
  • MAPK
  • Amines
  • Aromatics
  • Heterocycles
  • Inhibitors
  • Intermediates & Fine Chemicals
  • Pharmaceuticals
  • API
Mol File:
1236699-92-5.mol
More
Less

AS703026 Chemical Properties

Boiling point:
623.2±55.0 °C(Predicted)
Density 
1.769
storage temp. 
Store at -20°C
solubility 
≥21.55 mg/mL in DMSO; insoluble in H2O; ≥10.36 mg/mL in EtOH with ultrasonic
form 
solid
pka
12.82±0.46(Predicted)
color 
Light yellow to khaki
More
Less

Safety Information

HS Code 
2933399990
More
Less

AS703026 Usage And Synthesis

Uses

AS703026 is a novel, selective, orally bioavailable MEK1/2 inhibitor, in human multiple myeloma (MM). AS703026 induces pleiotropic anti-myeloma activity in vitro and in vivo. MEK inhibitors are useful in the treatment of hyperproliferative diseases, such as cancer, restenosis and inflammation.

Definition

ChEBI: N-[(2S)-2,3-dihydroxypropyl]-3-(2-fluoro-4-iodoanilino)-4-pyridinecarboxamide is a pyridinecarboxamide.

Biological Activity

the mek/erk pathway transmits mitogenic signals to the nucleus and thus regulates the expression of genes that are critical for survival, proliferation, and differentiation. this pathway is often upregulated in cancer as result of oncogenic mutations. mek is a crucial kinase in this pathway and has been targeted for the therapeutic agents development that block the mek/erk signaling cascade. as 703026 is a novel small molecule mek inhibitor.

in vitro

as 703026 binds to the distinctive mek allosteric site and therefore exhibits exquisite kinase selectivity. the as 703026 binding to mek is independent of atp, and results in enzyme inhibition by prevention of activation. this inhibitor shows strong antiproliferative effect on tumor cell lines bearing oncogenic mutations or amplifications along the mek/erk pathway [1].

Enzyme inhibitor

This novel and orally bioavailable MEK1/2 inhibitor (FW = 431.20 g/mol; CAS 1236699-92-5), also known as (S)-N-(2,3-dihydroxypropyl)-3-((2- fluoro-4-iodophenyl)amino)-isonicotinamide, selectively targets MEK1/2 (noncompetitive, with IC50 values of 5-11 nM). AS703026 reduces the growth and survival of multiple myeloma (MM) cells. It also inhibits cytokine-induced osteoclast differentiation about 10x more potently than AZD6244. Inhibition of proliferation by AS703026 leads to G0-G1 cell cycle arrest, attended by reduction in MAF oncogene expression. AS703026 also induces apoptosis (via Caspase-3) as well as poly(ADP- ribose) polymerase (PARP) cleavage in MM cells, whether in the absence or presence of bone marrow stromal cells (BMSCs). Importantly, AS703026 also sensitizes MM cells to other anti-MM therapies employing dexamethasone, melphalan, lenalidomide, perifosine, bortezomib, or rapamycin. Growth reduction in mice bearing H929 MM xenograft tumors correlates with down-regulated pERK1/2, induced PARP cleavage, and decreased microvasculature. BMSC-induced viability of MM patient cells was similarly blocked within the same dose range.

in vivo

in relevant mouse xenograft models, as 703026 inhibits tumor growth after oral administration. the effect on tumor growth is dose-dependant and correlates with target modulation in both tumors and blood [1].

target

MEK1/2

IC 50

ranging from 0.005 to 2 μm for the growth of mm cell lines

References

[1] goutopoulos a, askew bc, bankston d, clark a, dhanabal m, dong r, fischer d, healey b, jiang x, josephson k, lin j, ma j, noonan t, qiu d, rocha c, romanelli a, shutes a, spooner e, tian h, h y. as703026: a novel allosteric mek inhibitor. aacr annual meeting. 2009 abstract#4776.
[2] macarulla t, cervantes a, tabernero j et al. phase i study of folfiri plus pimasertib as second-line treatment for kras-mutated metastatic colorectal cancer. br j cancer. 2015 jun 9;112(12):1874-81.

AS703026Supplier

Wuxi KaideRui Pharmaceutical Technology Co., Ltd Gold
Tel
19906241957
Email
1557216087@qq.com
Wuxi Donghe Pharmaceutical Technology Co., Ltd. Gold
Tel
63313187 15358055255
Email
63313187@qq.com
Hangzhou Boronoda Biomedical Technology Co. LTD Gold
Tel
15107101114
Email
15107101114@139.com
Shanghai Boyle Chemical Co., Ltd.
Tel
Email
sales@boylechem.com
J & K SCIENTIFIC LTD.
Tel
010-82848833 400-666-7788
Email
jkinfo@jkchemical.com