(E)-Akt inhibitor-IV ((E)-AKTIV) is a PI3K-Akt inhibitor (antagonist) with significant cell toxicity/cytotoxicity.

Physicochemical Properties

Molecular Formula	C31H27IN4S
Molecular Weight	614.54
Exact Mass	614.1
Elemental Analysis	C, 60.59; H, 4.43; I, 20.65; N, 9.12; S, 5.22
CAS #	959841-49-7
Related CAS #	PF-AKT400;1004990-28-6;AKT inhibitor IV;681281-88-9
PubChem CID	163285845
Appearance	Yellow to green solid powder
Melting Point	165-167 °C
LogP	8.319
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	6
Heavy Atom Count	37
Complexity	732
Defined Atom Stereocenter Count	0
SMILES	CCN1C(N(C2=C1C=C(C=C2)C3=NC4=CC=CC=C4S3)C5=CC=CC=C5)/C=C/N(C)C6=CC=CC=C6.I
InChi Key	FIKDMAZMOIQHOO-ANVLNOONSA-N
InChi Code	InChI=1S/C31H28N4S.HI/c1-3-34-28-22-23(31-32-26-16-10-11-17-29(26)36-31)18-19-27(28)35(25-14-8-5-9-15-25)30(34)20-21-33(2)24-12-6-4-7-13-24;/h4-22,30H,3H2,1-2H3;1H/b21-20+;
Chemical Name	N-[(E)-2-[5-(1,3-benzothiazol-2-yl)-3-ethyl-1-phenyl-2H-benzimidazol-2-yl]ethenyl]-N-methylaniline;hydroiodide
Synonyms	959841-49-7; N-[(E)-2-[5-(1,3-benzothiazol-2-yl)-3-ethyl-1-phenyl-2H-benzimidazol-2-yl]ethenyl]-N-methylaniline;hydroiodide; SCHEMBL616785; orb1298127; SCHEMBL3488717;
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Akt[1]
ln Vitro	- Antiproliferative activity: (E)-Akt inhibitor-IV demonstrated potent cytotoxicity against cancer cell lines, with average GI20 values of 0.04 μM in MDA-MB-468 (breast cancer), MDA-MB-231 (breast cancer), and MCF7 (breast cancer) cells. Non-cancerous 184B5 mammary epithelial cells showed minimal sensitivity (GI20 > 10 μM) . - Mechanism of action: The compound induced apoptosis in cancer cells by upregulating pro-apoptotic proteins (e.g., BMF) and activating the JAK1-STAT3 pathway, while preserving non-cancer cell viability through selective targeting of PI3K-AKT hyperactivated tumor cells . (E)-Akt inhibitor-IV (Compound 7) exhibits an average GI20 of 0.04 μM on four distinct cell lines, namely MDA-MB468, MDA-MB231, MCF7, and 184B5 [1]. At an average GI20, (E)-Akt inhibitor-IV had minimal influence on the proliferation of 184B5 non-cancer cells [1].
Enzyme Assay	PI3K-AKT pathway inhibition: (E)-Akt inhibitor-IV was evaluated in cell-based kinase assays, where it reduced phosphorylation of AKT (Ser473) and its downstream target GSK-3β (Ser9) in a dose-dependent manner. The IC50 for AKT phosphorylation inhibition in MDA-MB-231 cells was 0.08 μM .
Cell Assay	- MTT proliferation assay: Cancer cells (5×10³/well) were treated with (E)-Akt inhibitor-IV (0.01–10 μM) for 72 hours. Cell viability was measured using MTT reagent, and GI20 values were calculated. The compound showed selective cytotoxicity toward cancer cells over non-cancerous 184B5 cells . - Apoptosis detection: Annexin V/PI staining revealed that (E)-Akt inhibitor-IV (0.1 μM) induced apoptosis in 35% of MDA-MB-231 cells after 24 hours, compared to 8% in vehicle-treated controls. This was accompanied by caspase-3 activation and PARP cleavage .
ADME/Pharmacokinetics	- Oral bioavailability: The compound exhibited moderate oral bioavailability (F = 35%) in preclinical models, with peak plasma concentrations (Cmax) achieved within 1–2 hours post-dose. Plasma protein binding was estimated at 92% . - Metabolism: (E)-Akt inhibitor-IV was primarily metabolized via hepatic cytochrome P450 enzymes (CYP3A4), with the major metabolite retaining 30% of the parent compound’s activity .
References	[1]. A 4-aminoquinoline derivative that markedly sensitizes tumor cell killing by Akt inhibitors with a minimum cytotoxicity to non-cancer cells. Eur J Med Chem. 2010 Feb;45(2):705-9.
Additional Infomation	- Structural optimization: The 4-aminoquinoline scaffold of (E)-Akt inhibitor-IV was optimized to enhance selectivity for PI3K-AKT hyperactivated tumors while minimizing off-target effects. The (E)-isomer configuration was critical for potency . - Therapeutic potential: The compound sensitized resistant cancer cells to AKT inhibitors (e.g., MK-2206), achieving synergistic cytotoxicity (combination index < 0.8) in triple-negative breast cancer models .

Solubility Data

Solubility (In Vitro)

DMSO: 50 mg/mL (81.36 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2 mg/mL (3.25 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	1.6272 mL	8.1362 mL	16.2723 mL
	5 mM	0.3254 mL	1.6272 mL	3.2545 mL
	10 mM	0.1627 mL	0.8136 mL	1.6272 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.