NTQ1062 is a potent and orally bioactive Akt inhibitor (antagonist) with IC50s of 0.4 nM, 6.3 nM and 0.1 nM for Akt1, Akt2 and Akt3, respectively. NTQ1062 causes apoptosis and arrests the cell cycle in the G0/G1 phase. NTQ1062 has antiproliferation activity against a variety of cancer/tumor cells. NTQ1062 displays potent anti-tumor activities in LNCap mouse xenograft models.

Physicochemical Properties

Molecular Formula	C25H31CLN6O2
Molecular Weight	483.01
Exact Mass	482.219
CAS #	2459489-66-6
PubChem CID	154663238
Appearance	Typically exists as solid at room temperature
LogP	2.6
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	6
Heavy Atom Count	34
Complexity	760
Defined Atom Stereocenter Count	4
SMILES	C[C@@H]1CC(=O)NC2=C1C(=NC=N2)N3CCN([C@H]4[C@@H]3C4)C(=O)[C@H](CNC(C)C)C5=CC=C(C=C5)Cl
InChi Key	RXNPEQZHMGFNAY-GEALJGNFSA-N
InChi Code	InChI=1S/C25H31ClN6O2/c1-14(2)27-12-18(16-4-6-17(26)7-5-16)25(34)32-9-8-31(19-11-20(19)32)24-22-15(3)10-21(33)30-23(22)28-13-29-24/h4-7,13-15,18-20,27H,8-12H2,1-3H3,(H,28,29,30,33)/t15-,18-,19+,20-/m1/s1
Chemical Name	(5R)-4-[(1S,6R)-5-[(2S)-2-(4-chlorophenyl)-3-(propan-2-ylamino)propanoyl]-2,5-diazabicyclo[4.1.0]heptan-2-yl]-5-methyl-6,8-dihydro-5H-pyrido[2,3-d]pyrimidin-7-one
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
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

ln Vitro	NTQ1062 (compound 22b) (0-4 μM; 72 hours) exhibits antiproliferative action against a variety of cancer cell lines [1]. LNCap cells undergo apoptosis when exposed to NTQ1062 (2.5 μM; 72 hours) [1]. LNCap cells are arrested in the G0-G1 phase by NTQ1062 (0.2 μM; 24 hours) [1].
ln Vivo	Tumor suppressant effects are demonstrated by NTQ1062 (12.5, 25 and 50 mg/kg; oral; once daily for 18–21 days) [1]. The pharmacokinetic properties of NTQ1062 (IV 5 mg/kg, IG 10 mg/kg; single dosage) are favorable [1]. NTQ1062 (compound 22b) pharmacokinetic characteristics in male Sprague-Dawley rats [1]. Tmax (h) 2 t1/2 (ng/mL) 2.97 3.28 Cmax (ng/mL) 1691 705 AUC0-t (ng/mL·h) 1761 3877 AUC0 -∞ (ng/mL·h) 1801 3891 VSS (L/kg) 7.76 F (%) 110
Cell Assay	Cell Proliferation Assay[1] Cell Types: CAL-51, T-47D, COLO-704, TOV-21G, C-33A and RL-95-2 Cell Line Tested Concentrations: 0-4μM Incubation Duration: 72 hrs (hours) Experimental Results: Presented It has strong inhibitory effect on CAL-51, T-47D, COLO-704, TOV-21G, C-33A and RL-95-2 cell lines, with IC50<300 nM. Apoptosis analysis [1] Cell Types: LNCap Cell Tested Concentrations: 2.5 μM Incubation Duration: 72 h Experimental Results: The total number of apoptotic cells reached 38.97%, while the control group was only 3.95%. Cell cycle analysis [1] Cell Types: LNCap Cell Tested Concentrations: 0.2 μM Incubation Duration: 24 h Experimental Results: 82.42% of the cells were in the G0-G1 phase, and the number of cells in the S phase and G2-M phase was diminished.
Animal Protocol	Animal/Disease Models: Male NCG mice (24-30 g; LNCap was inoculated subcutaneously (sc) (sc) in the right hind abdomen, density is 1×) 107 pcs cells/mL, 100 μL per mouse)[1] Doses: 12.5, 25, and 50 mg/kg Route of Administration: Oral; one time/day for 18-21 days Experimental Results: Demonstrated dose-dependent tumor suppression, 12.5 The TGI at , 25 and 50 mg/kg were 58.4%, 84.1% and 95.5% respectively.
References	[1]. Discovery of Clinical Candidate NTQ1062 as a Potent and Bioavailable Akt Inhibitor for the Treatment of Human Tumors. J Med Chem. 2022 Jun 23;65(12):8144-8168.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.0704 mL	10.3518 mL	20.7035 mL
	5 mM	0.4141 mL	2.0704 mL	4.1407 mL
	10 mM	0.2070 mL	1.0352 mL	2.0704 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.