[CAS NO. 1047645-82-8] Afuresertibhydrochloride

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PRODUCTS SPECIFICATIONS [1047645-82-8]

Catalog

HY-15727A

Brand

MCE

CAS

1047645-82-8

DESCRIPTION [1047645-82-8]

Overview

MDL	MFCD28167824
Molecular Weight	463.78
Molecular Formula	C18H18Cl3FN4OS
SMILES	O=C(C1=CC(C2=C(Cl)C=NN2C)=C(Cl)S1)N[C@@H](CC3=CC=CC(F)=C3)CN.[H]Cl

For research use only. We do not sell to patients.

11 Publications Citing Use of MCE

Summary

Afuresertib hydrochloride (GSK 2110183 hydrochloride) is an orally bioavailable, selective, ATP-competitive and potent pan-Akt kinase inhibitor with K _i s of 0.08/2/2.6 nM for Akt1/Akt2/Akt3 respectively ^[1] ^[2] .

IC50 & Target

Akt1

0.08 nM (Ki)

Akt2

2 nM (Ki)

Akt3

2.6 nM (Ki)

Akt1 E17K mutant

0.2 nM (IC ₅₀ )

PKCη

210 nM (IC ₅₀ )

PKC-βI

430 nM (IC ₅₀ )

ROCK

100 nM (IC ₅₀ )

PKCθ

510 nM (IC ₅₀ )

In Vitro

Afuresertib (GSK 2110183) exhibits favorable tumor-suppressive effects on malignant pleural mesothelioma (MPM) cells. Afuresertib significantly increases caspase-3 and caspase-7 activities and apoptotic cell number among ACC-MESO-4 and MSTO-211H cells. Afuresertib strongly arrests the cell cycle in the G ₁ phase.
Western blotting analysis shows that Afuresertib increases the expression of p21 ^WAF1/CIP1 and decreases the phosphorylation of Akt substrates, including GSK-3β and FOXO family proteins. Afuresertib-induced p21 expression promotes G ₁ phase arrest by inducing FOXO activity. Afuresertib significantly enhances cisplatin-induced cytotoxicity. Afuresertib modulates the expression E2F1 and MYC , which are associated with fibroblast core serum response ^[1] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Mice bearing BT474 breast tumor xenografts are dosed orally with either vehicle or GSK2110183 at 10, 30 or 100 mg/kg daily for 21 days which result in 8, 37 and 61% TGI, respectively. Mice tolerated GSK2110183 well, with 1-3% body weight loss reported after 5 days of dosing which recover over the course of the study. Other tumor xenograft models which possess an activation of the Akt pathway are explored to further demonstrate compound efficacy. Mice treated with GSK2110183 at 10, 30 and 100 mg/kg result in 23, 37 and 97% TGI, respectively, of SKOV3 xenografts ^[2] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase
NCT01532700	University Health Network, Toronto\|Novartis	Chronic Lymphocytic Leukemia (CLL)	February 2012	Phase 2
NCT04060394	Laekna Limited	Metastatic Castration-resistant Prostate Cancer	September 13, 2019	Phase 1\|Phase 2
NCT04851613	Laekna LLC\|Laekna Limited	Breast Cancer	February 18, 2022	Phase 1
NCT02040480	GlaxoSmithKline	Cancer	February 5, 2014	Phase 1
NCT01476137	GlaxoSmithKline	Cancer	October 26, 2011	Phase 1
NCT01653912	Accenture	Recurrent Platinum-resistant Ovarian Cancer	November 2012	Phase 1\|Phase 2
NCT02235740	Novartis\|Amgen	Cancer	November 2014	Phase 1
NCT01827644	GlaxoSmithKline	Cancer	April 24, 2013	Phase 1
NCT05383482	Laekna Limited	Solid Tumor\|NSCLC\|Cervical Cancer\|Endometrial Cancer\|Esophageal Cancer\|Gastric and Gastroesophageal Junction Adenocarcinoma	June 30, 2022	Phase 1\|Phase 2
NCT02177682	Novartis Pharmaceuticals\|Novartis	Neoplasms, Haematologic	August 13, 2014	Phase 1
NCT02240212	Novartis Pharmaceuticals\|Novartis	Cancer	October 2014	Phase 1
NCT05390710	Laekna Limited	Solid Tumor\|TNBC - Triple-Negative Breast Cancer	June 12, 2021	Phase 1\|Phase 2
NCT02380313	GlaxoSmithKline	Cancer	October 2015	Phase 1
NCT04374630	Laekna Limited	Platinum-resistant Ovarian Cancer	June 9, 2020	Phase 2
NCT01395004	GlaxoSmithKline	Langerhans Cell Histiocytosis	November 2011	Phase 2
NCT01428492	Novartis	Multiple Myeloma	December 2011	Phase 1
NCT01531894	Novartis Pharmaceuticals\|Novartis	Cancer	February 8, 2012	Phase 2

Appearance

Solid

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

-20°C, protect from light, stored under nitrogen

* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light, stored under nitrogen)

Solvent & Solubility

In Vitro:

DMSO : 100 mg/mL ( 215.62 mM ; Need ultrasonic)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

1 mM	2.1562 mL	10.7810 mL	21.5619 mL
5 mM	0.4312 mL	2.1562 mL	4.3124 mL
10 mM	0.2156 mL	1.0781 mL	2.1562 mL

* Please refer to the solubility information to select the appropriate solvent.

In Vivo:

1.

Add each solvent one by one: 10% DMSO >> 40% PEG300 >> 5% Tween-80 >> 45% saline

Solubility: ≥ 2.5 mg/mL (5.39 mM); Clear solution
2.

Add each solvent one by one: 10% DMSO >> 90% (20% SBE-β-CD in saline)

Solubility: ≥ 2.5 mg/mL (5.39 mM); Clear solution
3.

Add each solvent one by one: 10% DMSO >> 90% corn oil

Solubility: ≥ 2.5 mg/mL (5.39 mM); Clear solution

* All of the co-solvents are available by MCE.