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Merck
모든 사진(1)

주요 문서

SML2394

Sigma-Aldrich

AT9283

≥98% (HPLC)

동의어(들):

1-Cyclopropyl-3-[3-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-urea, AT 9283, AT-9283, N-Cyclopropyl-N′-[3-[6-(4-morpholinylmethyl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl]-urea

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About This Item

실험식(Hill 표기법):
C19H23N7O2
CAS Number:
Molecular Weight:
381.43
MDL number:
UNSPSC 코드:
12352200
NACRES:
NA.77

분석

≥98% (HPLC)

양식

powder

색상

white to beige

solubility

DMSO: 2 mg/mL, clear

저장 온도

−20°C

SMILES string

[nH]1nc(c(c1)NC(=O)NC5CC5)c2[nH]c3c(n2)ccc(c3)CN4CCOCC4

InChI

1S/C19H23N7O2/c27-19(21-13-2-3-13)24-16-10-20-25-17(16)18-22-14-4-1-12(9-15(14)23-18)11-26-5-7-28-8-6-26/h1,4,9-10,13H,2-3,5-8,11H2,(H,20,25)(H,22,23)(H2,21,24,27)

InChI key

LOLPPWBBNUVNQZ-UHFFFAOYSA-N

생화학적/생리학적 작용

A multitargeted kinase inhibitor with in vivo anticancer efficacy and potent activity against Abl, aurora kinase A/B and JAK2/3.
AT9283 has also been shown to accelerate growth arrest in various xenograft models.
AT9283 is an ATP site-targeting pyrazole-benzimidazole-based molecule with inhibitory potency against multiple kinases, most notably Aurora A/B (IC50 ≤3.0 nM), JAK2/3 (IC50 = 1.2/1.1 nM), Abl T315I (IC50 = 4 nM), GSK3β, FGFR2, VEGFR3 (Flt4), Mer, Ret, Rsk2/3, Tyk2, Yes (IC50 = 1-10 nM). AT9283 also inhibits 72 other kinases/mutations at a reduced potency (IC50 = 10-30 nM against 14, 30-100 nM against 21, 100-300 against 37 targets), while displaying an IC50 >300 nM toward 144 other kinase targets. AT9283 inhibits the growth/survival of multiple solid tumor cell lines in vitro (IC50 = 7.7-20 nM) and shows anti-cancer efficacy in mice via i.p. injection in vivo (67% and 76%HCT116 tumor growth inhibition on day 16, respectively, with 15 and 20 mg/kg b.i.d., two-day on and two-day off; >95% inhibition of Ba/F3 ETV6-JAK2 leukemia proliferation on day 12 with 10 mg/kg b.i.d. on days 2–5 and 8–12).

Storage Class Code

11 - Combustible Solids

WGK

WGK 3

Flash Point (°F)

Not applicable

Flash Point (°C)

Not applicable


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시험 성적서(COA)

Lot/Batch Number

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문서 라이브러리 방문

Mark A Dawson et al.
British journal of haematology, 150(1), 46-57 (2010-05-29)
Constitutive activation of Janus kinase (Jak) 2 is the most prevalent pathogenic event observed in the myeloproliferative disorders (MPD), suggesting that inhibitors of Jak2 may prove valuable in their management. Inhibition of the Aurora kinases has also proven to be
Ruriko Tanaka et al.
Blood, 116(12), 2089-2095 (2010-06-16)
Despite promising clinical results from imatinib mesylate and second-generation ABL tyrosine kinase inhibitors (TKIs) for most BCR-ABL(+) leukemia, BCR-ABL harboring the mutation of threonine 315 to isoleucine (BCR-ABL/T315I) is not targeted by any of these agents. We describe the in
Hannah C Feldman et al.
ACS chemical biology, 11(8), 2195-2205 (2016-05-27)
The accumulation of unfolded proteins under endoplasmic reticulum (ER) stress leads to the activation of the multidomain protein sensor IRE1α as part of the unfolded protein response (UPR). Clustering of IRE1α lumenal domains in the presence of unfolded proteins promotes
Jihoon Shin et al.
eLife, 5, e10877-e10877 (2016-02-18)
Pluripotency transcription programs by core transcription factors (CTFs) might be reset during M/G1 transition to maintain the pluripotency of embryonic stem cells (ESCs). However, little is known about how CTFs are governed during cell cycle progression. Here, we demonstrate that
Steven Howard et al.
Journal of medicinal chemistry, 52(2), 379-388 (2009-01-16)
Here, we describe the identification of a clinical candidate via structure-based optimization of a ligand efficient pyrazole-benzimidazole fragment. Aurora kinases play a key role in the regulation of mitosis and in recent years have become attractive targets for the treatment

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