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Samotolisib 99%+

货号:A173638 同义名: LY3023414;GTPL8918 Ambeed 开学季,买赠积分,赢豪礼

LY3023414 is an oral ATP competitive inhibitor of the class I PI3K isoforms, mTOR and DNA-PK with an IC50 of 64.9 nM, 42.1 nM, 10.6 nM, 19.1 nM for Akt1 (pT308), Akt1 (pS473), P70S6 (pT389), S6RP (pS240/242).

Samotolisib 化学结构 CAS号:1386874-06-1
Samotolisib 化学结构
CAS号:1386874-06-1
Samotolisib 3D分子结构
CAS号:1386874-06-1
Samotolisib 化学结构 CAS号:1386874-06-1
Samotolisib 3D分子结构 CAS号:1386874-06-1
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Samotolisib 纯度/质量文件 产品仅供科研

货号:A173638 标准纯度: 99%+
批次查询: 批次纯度:

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产品名称 C2β p110α p110β p110γ p110δ PI3K Vps34 其他靶点 纯度
A66 +

C2β, IC50: 462 nM

++

p110α, IC50: 32 nM

99%+
Taselisib +

C2β, IC50: 292 nM

++++

PI3Kα, Ki: 0.29 nM

+++

PI3Kβ, Ki: 9.1 nM

++++

PI3Kγ, Ki: 0.97 nM

++++

PI3Kδ, Ki: 0.12 nM

+

hVps34, IC50: 374 nM

99%+
Gedatolisib ++++

PI3Kα, IC50: 0.4 nM

+++

PI3Kγ, IC50: 5.4 nM

mTOR 99%+
HS-173 ++++

PI3Kα , IC50: 0.8 nM

99%+
Serabelisib +++

PI3Kα, IC50: 21 nM

99%+
GNE-477 ++++

PI3Kα, IC50: 4 nM

mTOR 99%+
YM-201636 +

p110α, IC50: 3.3 μM

PIKfyve 99%+
AS-252424 +

PI3Kα, IC50: 935 nM

++

PI3Kγ, IC50: 33 nM

99%
Alpelisib +++

PI3Kα, IC50: 5 nM

99%+
AS-604850 +

PI3Kα, IC50: 4.5 μM

+

PI3Kγ, IC50: 0.25 μM

99%+
SF2523 ++

PI3Kα, IC50: 34 nM

++

PI3Kγ, IC50: 158 nM

DNA-PK,mTOR 99%+
Inavolisib ++++

PI3K alpha, IC50: 0.038 nM

99%+
Bimiralisib ++++

PI3Kα, Kd: 1.5 nM

+++

PI3Kβ, Kd: 11 nM

++

PI3Kγ, Kd: 25 nM

++

PI3Kδ, Kd: 25 nM

mTOR 99%+
GSK1059615 ++++

PI3Kα, IC50: 0.4 nM

++++

PI3Kβ, IC50: 0.6 nM

+++

PI3Kγ, IC50: 5 nM

++++

PI3Kδ, IC50: 2 nM

mTOR 98%
GSK2636771 99%+
Fimepinostat +++

PI3Kα, IC50: 19 nM

++

PI3Kβ, IC50: 54 nM

++

PI3Kδ, IC50: 39 nM

99%+
VS-5584 ++++

PI3Kα, IC50: 2.6 nM

+++

PI3Kβ, IC50: 21 nM

++++

PI3Kγ, IC50: 3.0 nM

++++

PI3Kδ, IC50: 2.7 nM

mTOR 99%
Dactolisib ++++

p110α1, IC50: 4 nM

++

p110β, IC50: 75 nM

+++

p110γ, IC50: 5 nM

+++

p110δ, IC50: 7 nM

99%+
PI-103 ++++

p110α, IC50: 2 nM

++++

p110β, IC50: 3 nM

+++

p110γ, IC50: 15 nM

++++

p110δ, IC50: 3 nM

DNA-PK,mTOR 99%+
PI-3065 +

p110β, IC50: 1078 nM

+++

p110δ, IC50: 15 nM

99%+
Voxtalisib ++

PI3Kα, IC50: 39 nM

++

PI3Kβ, IC50: 113 nM

+++

PI3Kγ, IC50: 9 nM

++

PI3Kδ, IC50: 43 nM

DNA-PK,mTOR 99%+
AZD-8835 +++

PI3Kα, IC50: 6.2 nM

+

PI3Kβ, IC50: 431 nM

++

PI3Kγ, IC50: 90 nM

+++

PI3Kδ, IC50: 5.7 nM

99%+
Pilaralisib analogue ++

PI3Kα, IC50: 39 nM

++

PI3Kβ, IC50: 36 nM

+++

PI3Kγ, IC50: 23 nM

++

PI3Kδ, IC50: 36 nM

99%+
ZSTK474 +++

PI3Kα, IC50: 16 nM

++

PI3Kβ, IC50: 44 nM

++

PI3Kγ, IC50: 49 nM

+++

PI3Kδ, IC50: 4.6 nM

++

PI3K, IC50: 37 nM

99%+
AS-605240 ++

PI3Kα, IC50: 60 nM

+

PI3Kβ, IC50: 270 nM

+++

PI3Kγ, IC50: 8 nM

+

PI3Kδ, IC50: 300 nM

99%+
TGX-221 +++

p110β, IC50: 5 nM

++

p110δ, IC50: 0.1 μM

99%+
PF-04691502 ++++

PI3Kα, Ki: 1.8 nM

++++

PI3Kβ, Ki: 2.1 nM

++++

PI3Kγ, Ki: 1.9 nM

++++

PI3Kδ, Ki: 1.6 nM

mTOR 99%+
GDC-0084 ++++

PI3Kα, Ki app: 2 nM

++

PI3Kβ, Ki app: 46 nM

+++

PI3Kγ, Ki app: 10 nM

++++

PI3Kδ, Ki app: 3 nM

mTOR 99%+
Buparlisib ++

p110α, IC50: 52 nM

+

p110β, IC50: 166 nM

+

p110γ, IC50: 262 nM

++

p110δ, IC50: 116 nM

+

Vps34, IC50: 2.4 μM

mTOR 98%
LY294002 +

p110α, IC50: 0.5 μM

+

p110β, IC50: 0.97 μM

+

p110δ, IC50: 0.57 μM

DNA-PK 99%+
AZD 6482 +

PI3Kα, IC50: 870 nM

+++

PI3Kβ, IC50: 10 nM

++

PI3Kδ, IC50: 80 nM

DNA-PK 99%+
Pictilisib ++++

p110α, IC50: 3 nM

++

p110β, IC50: 33 nM

++

p110γ, IC50: 75 nM

++++

p110δ, IC50: 3 nM

mTOR 99%+
PKI-402 ++++

PI3Kα, IC50: 2 nM

+++

PI3Kβ, IC50: 7 nM

+++

PI3Kγ, IC50: 16 nM

+++

PI3Kδ, IC50: 14 nM

mTOR 99+%
Copanlisib ++++

PI3Kα, IC50: 0.5 nM

++++

PI3Kβ, IC50: 3.7 nM

+++

PI3Kγ, IC50: 6.4 nM

++++

PI3Kδ, IC50: 0.7 nM

99%+
Omipalisib ++++

p110α, Ki: 0.019 nM

++++

p110β, Ki: 0.13 nM

++++

p110γ, Ki: 0.06 nM

++++

p110δ, Ki: 0.024 nM

99%+
Izorlisib +++

PI3Kα, IC50: 14 nM

++

PI3Kβ, IC50: 0.12 μM

++

PI3Kγ, IC50: 36 nM

+

PI3Kδ, IC50: 0.50 μM

99%+
AZD8186 ++

PI3Kα, IC50: 35 nM

++++

PI3Kβ, IC50: 4 nM

+++

PI3Kδ, IC50: 12 nM

99%+
KU-0060648 ++++

PI3Kα, IC50: 4 nM

++++

PI3Kβ, IC50: 0.5 nM

+

PI3Kγ, IC50: 0.59 μM

++++

PI3Kδ, IC50: 0.1 nM

DNA-PK 99%
Apitolisib +++

p110α, IC50: 5 nM

++

p110β, IC50: 27 nM

+++

p110γ, IC50: 14 nM

+++

p110δ, IC50: 7 nM

mTOR 99%+
CZC24832 +

PI3Kβ, IC50: 1.1 μM

++

PI3Kγ, IC50: 27 nM

99%+
BGT226 maleate ++++

PI3Kα, IC50: 4 nM

++

PI3Kβ, IC50: 63 nM

++

PI3Kγ, IC50: 38 nM

mTOR 99%+
TG 100713 ++

PI3Kα, IC50: 165 nM

+

PI3Kβ, IC50: 215 nM

++

PI3Kγ, IC50: 50 nM

+++

PI3Kδ, IC50: 24 nM

99%+
PI3K-IN-1 ++

PI3Kα, IC50: 39 nM

++

PI3Kβ, IC50: 113 nM

+++

PI3Kγ, IC50: 9 nM

++

PI3Kδ, IC50: 43 nM

DNA-PK,mTOR 99%+
TG100-115 +

PI3Kα, IC50: 1.3 μM

+

PI3Kβ, IC50: 1.2 μM

++

PI3Kγ, IC50: 83 nM

+

PI3Kδ, IC50: 235 nM

99%+
PIK-90 +++

PI3Kα, IC50: 11 nM

+

PI3Kβ, IC50: 350 nM

+++

PI3Kγ, IC50: 18 nM

++

PI3Kδ, IC50: 58 nM

99%+
PIK-294 +

p110β, IC50: 490 nM

++

p110γ, IC50: 160 nM

+++

p110δ, IC50: 10 nM

99%+
Duvelisib ++++

PI3Kβ, Ki: 1564 pM

++

PI3Kγ, Ki: 243 pM

++++

PI3Kδ, Ki: 23 pM

99%+
GDC-0326 ++++

PI3Kα, Ki: 0.2 nM

++

PI3Kβ, Ki: 26.6 nM

+++

PI3Kγ, Ki: 10.2 nM

++++

PI3Kδ, Ki: 4 nM

98%
Quercetin Dihydrate +

PI3Kβ, IC50: 5.4 μM

+

PI3Kγ, IC50: 2.4 μM

+

PI3Kδ, IC50: 3.0 μM

98%+
Quercetin +

PI3Kβ, IC50: 5.4 μM

+

PI3Kγ, IC50: 2.4 μM

+

PI3Kδ, IC50: 3.0 μM

Src,PKC,Sirtuin 97%
Leniolisib +

PI3Kα, IC50: 0.244 μM

+

PI3Kβ, IC50: 0.424 μM

+

PI3Kγ, IC50: 2.23 μM

+++

PI3Kδ, IC50: 0.011 μM

DNA-PK 99%+
PIK-108 99%+
Eganelisib +++

PI3Kγ, IC50: 16 nM

99%+
CAY10505 99%+
IPI-3063 ++++

p110δ, IC50: 2.5 nM

99%
Nemiralisib ++++

PI3Kδ, pKi: 9.9

99%+
PF-4989216 ++++

p110α, IC50: 2 nM

++

p110γ, IC50: 65 nM

++++

p110δ, IC50: 1 nM

99%+
PIK-75 HCl +++

p110α, IC50: 5.8 nM

++

p110γ, IC50: 76 nM

+

p110δ, IC50: 0.51 μM

DNA-PK 99%+
Tenalisib ++

PI3Kγ, IC50: 33.2 nM

++

PI3Kδ, IC50: 24.5 nM

98%+
Acalisib +++

p110δ, IC50: 14 nM

99%+
Umbralisib +++

PI3Kδ, IC50: 22.2 nM

99%+
AMG319 +

PI3Kγ, IC50: 850 nM

+++

PI3Kδ, IC50: 18 nM

99%
IC-87114 +

PI3Kγ, IC50: 29 μM

+

PI3Kδ, IC50: 0.5 μM

99%+
Idelalisib ++

p110γ, IC50: 89 nM

++++

p110δ, IC50: 2.5 nM

98%
PIK-293 +

p110γ, IC50: 10 μM

+

p110δ, IC50: 0.24 μM

99%+
Vps34-PIK-III +

PI3Kδ, IC50: 1.2μM

+++

Vps34, IC50: 0.018μM

99%+
GSK2292767 99+%
Seletalisib +

PI3Kγ, IC50: 282 nM

+++

PI3Kδ, IC50: 12 nM

99%+
P110δ-IN-1 ++++

P110δ, IC50: 0.6 nM

99%+
PI3Kδ-IN-5 ++++

PI3Kδ, IC50: 0.9 nM

99%+
SRX3207 +

PI3K alpha, IC50: 244 nM

+

PI3K gamma, IC50: 9790 nM

+

PI3K delta, IC50: 388 nM

Syk 98%
Parsaclisib HCl ++++

PI3Kδ, IC50: 1 nM

98%
IHMT-PI3Kδ-372 +++

PI3Kδ, IC50: 14 nM

98%
Trigonelline Akt 99%+
Wortmannin ++++

PI3K, IC50: 3 nM

DNA-PK,MLCK 99%+
Samotolisib DNA-PK 99%+
GNE-317 99%+
Oroxin B Akt,PTEN 99%+
NU 7026 +

PI3K, IC50: 13 μM

DNA-PK 99%+
Deguelin Akt 99%+
Ailanthone CDK,Akt,ATM/ATR 98%
Resibufogenin ROS 98%
KU-57788 +

PI3K, IC50: 5 μM

DNA-PK,mTOR 99%+
Cinobufagine Akt 98%
α-Linolenic acid 97% GC
MTX-211 EGFR 99%+
PI3K/mTOR Inhibitor-2 ++++

PI3K, IC50: 3.4 nM

mTOR 99%+
SPP-86 99%+
(E)-Akt inhibitor-IV 98%
Vps34-IN-1 ++

Vps34, IC50: 25 nM

98%
SAR405 ++++

Vps34, IC50: 1.2 nM

99%+
3-Methyladenine +

PI3Kγ, IC50: 60 μM

+

Vps34, IC50: 25 μM

Autophagy 98%
Vps34-IN-4 +++

VPS34, IC50: 15 nM

99%+
Autophinib +++

Vps34, IC50: 19 nM

Autophagy 99%+
1. 鼠标悬停在“+”上可以显示相关IC50的具体数值。"+"越多,抑制作用越强。2. "✔"表示该化合物对相应的亚型有抑制作用,但抑制强度暂时没有相关数据。
产品名称 Akt Akt1 Akt2 Akt3 其他靶点 纯度
Honokiol MEK 98%
PF-04691502 ++++

P-Akt (T308), IC50: 7.5 nM

P-Akt (S473), IC50: 3.8 nM

99%+
PHT-427 +

Akt, Ki: 2.7 μM

99%+
Deguelin PI3K 99%+
TIC10 isomer ERK 98+%
Perifosine +

Akt, IC50: 4.7 μM

98%
Miltefosine PI3K,PKC 99%+
Triciribine +

Akt, IC50: 130 nM

99%+
Uprosertib +

Akt1, IC50: 180 nM

+

Akt2, IC50: 328 nM

++

Akt3, IC50: 38 nM

99%+
Afuresertib ++++

Akt1, Ki: 0.08 nM

++++

Akt2, Ki: 2 nM

++++

Akt3, Ki: 2.6 nM

99%+
Miransertib ++++

Akt1, IC50: 5 nM

++++

Akt2, IC50: 4.5 nM

++

Akt3, IC50: 16 nM

98+%
GSK-690693 ++++

Akt1, IC50: 2 nM

+++

Akt2, IC50: 13 nM

+++

Akt3, IC50: 9 nM

99%+
AT7867 ++

Akt1, IC50: 32 nM

++

Akt2, IC50: 17 nM

++

Akt3, IC50: 47 nM

PKA 99%+
AKT inhibitor VIII ++

Akt1, IC50: 58 nM

+

Akt2, IC50: 210 nM

+

Akt3, IC50: 2119 nM

98+%
MK-2206 2HCl +++

Akt1, IC50: 8 nM

+++

Akt2, IC50: 12 nM

+

Akt3, IC50: 65 nM

99%+
Ipatasertib ++++

Akt1, IC50: 5 nM

++

Akt2, IC50: 18 nM

+++

Akt3, IC50: 8 nM

99%+
AT13148 ++

Akt1, IC50: 38 nM

+

Akt2, IC50: 402 nM

++

Akt3, IC50: 50 nM

PKA 98+%
Capivasertib ++++

Akt1, IC50: 3 nM

+++

Akt2, IC50: 8 nM

+++

Akt3, IC50: 8 nM

99%+
A-674563 HCl +++

Akt1, Ki: 11 nM

PKA 99%+
CCT128930 +++

Akt2, IC50: 6 nM

PKA 98+%
1. 鼠标悬停在“+”上可以显示相关IC50的具体数值。"+"越多,抑制作用越强。2. "✔"表示该化合物对相应的亚型有抑制作用,但抑制强度暂时没有相关数据。
产品名称 DNA-PK 其他靶点 纯度
PI-103 ++

DNA-PK, IC50: 23 nM

99%+
CC-115 +++

DNA-PK, IC50: 0.013 μM

mTOR 99%+
Samotolisib 99%+
NU 7026 +

DNA-PK, IC50: 0.23 μM

PI3K 99%+
PIK-75 HCl ++++

DNA-PK, IC50: 2 nM

99%+
PP121 +

DNA-PK, IC50: 60 nM

VEGFR,PDGFR 99%+
KU-0060648 ++++

DNA-PK, IC50: 5 nM

99%
KU-57788 +++

DNA-PK, IC50: 14 nM

99%+
LTURM34 ++

DNA-PK, IC50: 0.034 μM

99%+
SF2523 +++

DNA-PK, IC50: 9 nM

99%+
1. 鼠标悬停在“+”上可以显示相关IC50的具体数值。"+"越多,抑制作用越强。2. "✔"表示该化合物对相应的亚型有抑制作用,但抑制强度暂时没有相关数据。

Samotolisib 生物活性

靶点
  • PI3K

  • mTOR

  • DNA-PK

描述 The PI3K/AKT/mTOR pathway is among the most frequently altered pathways in cancer cell growth and survival. LY3023414 is a complex fused imidazoquinolinone with high solubility across a wide pH range designed to inhibit class I PI3K isoforms and mTOR kinase. The IC50 values of LY3023414 towards PI3K family members are 6.07 nM, 77.6 nM, 38 nM, 23.8 nM, 4.24 nM and 165 nM for PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ, DNA-PK and mTOR, respectively. The compound is a novel, potent ATP-competitive inhibitor that demonstrates activity against PI3K, mTOR, and DNA-PK, thereby inducing cell-cycle effects and inhibiting cancer cell viability. Downstream target inhibition by LY3023414 occurs rapidly via an intermittent “on/off” mechanism that may enhance the drug's clinical tolerability, which may in turn allow LY3023414 to overcome some of the toxicities associated with PI3K/mTOR inhibitors and potentially reduce the emergence of feedback mechanisms leading to resistance. In vitro, inhibition of PI3K/AKT/mTOR signaling by LY3023414 caused G1 cell-cycle arrest and resulted in broad antiproliferative activity in cancer cell panel screens. In vivo, LY3023414 demonstrated high bioavailability and dose-dependent dephosphorylation of PI3K/AKT/mTOR pathway downstream substrates such as AKT, S6K, S6RP, and 4E-BP1 for 4 to 6 hours. In vivo mouse studies, LY3023414 was formulated in 1% HEC in distilled water containing 0.25% polysorbate 80 and 0.05% Dow-Corning Antifoam 1510-US and administered by oral gavage (final volume 0.2 mL) at 3, 6, or 10 mg/kg twice daily for 28 days which resulted in dose-responsive inhibition of tumor growth in the PTEN-deleted U87 MG xenograft model[4].
作用机制 The compound binds in a pocket bounded by side-chain residues of Met953 and Ile963 on one side and Trp812 and Ile831 on the other. It makes a hydrogen bond with the main-chain amide of Val882 and a CH···O interaction with the main-chain carbonyl of Glu880. It additionally interacts with the tyrosine hydroxyl of Tyr867 and the main-chain amide and side-chain of Asp964[4].

Samotolisib 动物研究

Dose Mice: 25 mg/kg[3] (p.o.); 6 mg/kg[1] (i.v.) Rat: 10 mg/kg[1] (p.o.)
Administration p.o., i.v.
Pharmacokinetics
Animal Mice Rats Dogs
Dose 6 mg/kg 3 mg/kg (i.v.)
10 mg/kg (p.o.)
3 mg/kg
Administration i.v. i.v.
p.o.
i.v.
p.o.
AUC0→inf 4580 ng·h/ml 5010 ± 765 ng/ml (i.v.)
4920 ± 604 ng/ml (p.o.)
AUC0→24h 4570 ng·h/ml 2300 ± 143 ng·h/ml (i.v.)
7420 ± 1280 ng·h/ml (p.o.)
5010 ± 765 ng/ml (i.v.)
4920 ± 604 ng/ml (p.o.)
T1/2 2.8 h 1.4 ± 0.2 (i.v.)
2.1 ± 0.5 (p.o.)
1.0 ± 0.3 (i.v.)
1.1 ± 0.1 (p.o.)
Tmax 0.3 ± 0.1 (p.o.) 0.9 ± 0.8 (p.o.)
AUC0-inf 2300 ± 137 ng·h/ml (i.v.)
7420 ± 1280 ng·h/ml (p.o.)
CL 22 ml/min/kg 22 ± 1 ng/ml (i.v.) 10 ± 2 ng/ml (i.v.)
Cmax 5410 ng/ml 1714 ± 308 ng/ml (i.v.)
3300 ± 492 ng/ml (p.o.)
3018 ± 614 ng/ml (i.v.)
1320 ± 261 ng/ml (p.o.)
Vdss 2560 ml/kg 2760 ± 317 ml/kg (i.v.) 1200 ± 164 ml/kg (i.v.)
F 97 ± 15% (p.o.) 100 ± 19% (p.o.)

Samotolisib 参考文献

[1]Smith MC, Mader MM, et al. Characterization of LY3023414, a Novel PI3K/mTOR Dual Inhibitor Eliciting Transient Target Modulation to Impede Tumor Growth. Mol Cancer Ther. 2016 Oct;15(10):2344-2356.

[2]Zaidi AH, Kosovec JE, et al. PI3K/mTOR Dual Inhibitor, LY3023414, Demonstrates Potent Antitumor Efficacy Against Esophageal Adenocarcinoma in a Rat Model. Ann Surg. 2017 Jul;266(1):91-98.

[3]Zheng L, Li H, et al. Autophagy inhibition sensitizes LY3023414-induced anti-glioma cell activity in vitro and in vivo. Oncotarget. 2017 Oct 27;8(58):98964-98973.

[4]Smith MC, Mader MM, Cook JA, Iversen P, Ajamie R, Perkins E, Bloem L, Yip YY, Barda DA, Waid PP, Zeckner DJ, Young DA, Sanchez-Felix M, Donoho GP, Wacheck V. Characterization of LY3023414, a Novel PI3K/mTOR Dual Inhibitor Eliciting Transient Target Modulation to Impede Tumor Growth. Mol Cancer Ther. 2016 Oct;15(10):2344-2356.

Samotolisib 实验方案

计算器
存储液制备 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.46mL

0.49mL

0.25mL

12.30mL

2.46mL

1.23mL

24.60mL

4.92mL

2.46mL

Samotolisib 技术信息

CAS号1386874-06-1
分子式C23H26N4O3
分子量 406.478
别名 LY3023414;GTPL8918
运输蓝冰
存储条件

粉末 Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月

溶解度

DMSO: 50 mg/mL(123.01 mM),配合低频超声助溶,注意:DMSO长时间开封后,会吸水并导致溶解能力下降,请避免使用长期开封的DMSO

动物实验配方
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