CDK6/PIM1-IN-1 is a potent and balanced dual CDK6/PIM1 inhibitor (antagonist) with IC50 of 39 nM and 88 nM, respectively. CDK6/PIM1-IN-1 inhibits CDK4 (IC50=3.6 nM). CDK6/PIM1-IN-1 can significantly inhibit acute myeloid leukemia (AML) cell growth/proliferation, arrest the cell cycle in the G1 phase, and promote cell apoptosis. CDK6/PIM1-IN-1 has anti-AML activity.

Physicochemical Properties

Molecular Weight	473.548526763916
Exact Mass	473.245
CAS #	2677026-14-9
PubChem CID	163196279
Appearance	Typically exists as solid at room temperature
LogP	3
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	10
Rotatable Bond Count	7
Heavy Atom Count	35
Complexity	646
Defined Atom Stereocenter Count	0
InChi Key	SKOICOFQIQHEPE-UHFFFAOYSA-N
InChi Code	InChI=1S/C25H28FN9/c1-3-34(4-2)23-16-28-20-7-5-17(13-21(20)31-23)24-19(26)15-30-25(33-24)32-22-8-6-18(14-29-22)35-11-9-27-10-12-35/h5-8,13-16,27H,3-4,9-12H2,1-2H3,(H,29,30,32,33)
Chemical Name	N,N-diethyl-7-[5-fluoro-2-[(5-piperazin-1-ylpyridin-2-yl)amino]pyrimidin-4-yl]quinoxalin-2-amine
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	Compared to CDK1 (IC50>10 μM), CDK2 (IC50=2.274 μM), CDK3 (IC50>10 μM), and CDK5 (IC50>10 μM), CDK6/PIM1-IN-1 (compound 51) has selectivity that is more than ten times higher. CDK9 (IC50=440 nM), CDK12 (IC50>10 μM), CDK13 (IC50>10 μM), CDK7 (IC50=393 nM), and so on. Inhibitory activity against PIM2 (IC50>10 μM) and PIM3 (IC50=92 nM) is demonstrated by CDK6/PIM1-IN-1 [1]. AML cell growth (K562 cells, GI50=1.026 μM; HL-60 cells, GI50=1.069 μM; MOLM13 cells, GI50=1.362 μM) is inhibited by CDK6/PIM1-IN-1 [1]. G1 arrest is caused in K562 and HL-60 cell lines in a dose-dependent manner by CDK6/PIM1-IN-1 (0.5, 1, 1.5 μM) [1]. A dose-dependent manner is shown in the promotion of apoptosis in K562 and HL-60 cell lines by CDK6/PIM1-IN-1 (1, 2, 4 μM). In a concentration-dependent manner, CDK6/PIM1-IN-1 (0.5, 1, 1.5 μM) decreased p-retinoblastoma (RB) and p-BAD levels throughout the course of 24 hours. PIM1 levels are lowered by CDK6/PIM1-IN-1 [1].
ln Vivo	CDK6/PIM1-IN-1 (compound 51; oral; 60, 90 mg/kg/day; 17 days) revealed more effective anticancer action in BALB/c mice with K562 cell line [1]. The t1/2, MRT0-∞ and AUC0-∞ values of CDK6/PIM1-IN-1 (iv; 5 mg/kg) in Sprague–Dawley are 9.78 h, 14.61 h and 1153.74 h·ng/mL (SD), respectively Rat[1]. The t1/2, Tmax, Cmax and AUC0-∞ of CDK6/PIM1-IN-1 (oral; 5 mg/kg) were 15.81 h, 11 h, 152.31 ng/mL and 5152.92 h·ng/mL, respectively, in SD rats in [1].
References	[1]. Discovery of Dual CDK6/PIM1 Inhibitors with a Novel Structure, High Potency, and Favorable Druggability for the Treatment of Acute Myeloid Leukemia. J Med Chem. 2022 Jan 13;65(1):857-875.

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	2.1117 mL	10.5585 mL	21.1171 mL
	5 mM	0.4223 mL	2.1117 mL	4.2234 mL
	10 mM	0.2112 mL	1.0559 mL	2.1117 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.