CDK4/6-IN-14 is a potent and selective inhibitor of CDK4 and CDK6 (CDK) with IC50 of 10 nM and 16 nM, respectively. CDK4/6-IN-14 is more than 60-fold more selective than CDKs 1, 2, 7, and 9 and displays high selectivity among 205 other kinases.

Physicochemical Properties

CAS #	2699091-15-9
Appearance	Typically exists as solid at room temperature
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

Targets	CDK4 10 nM (IC50) CDK6 16 nM (IC50) CDK1 >10000 nM (IC50) CDK2 1045 nM (IC50) CDK7 2595 nM (IC50) CDK9 2664 nM (IC50)
ln Vitro	Compound 42, CDK4/6-IN-14 (1-6 μM; 5 days) has strong anti-proliferative effects on the breast cancer cell lines MCF-7, T47D, and ZR-75-1. MCF-7 and T47D cell proliferation and clone formation are markedly inhibited by CDK4/6-IN-14[1]. In a dose-dependent manner, CDK4/6-IN-14 (compound 42; 1-6 μM) stops the cell cycle at the G1 phase in MCF-7 and T47D cells[1]. Compound 42, CDK4/6-IN-14, effectively reduces retinoblastoma (RB) phosphorylation at 1-6 μM for 24 hours, without significantly altering RB protein production. Moreover, CDK4/6-IN-14 has a concentration-dependent influence on cyclin D1 and c-MYC levels[1].
ln Vivo	CDK4/6-IN-14 (compound 42; 100-150 mg/kg; po; once daily; for 23 days) dramatically suppresses the MCF-7 xenograft model's ability to grow tumors[1]. Compound 42, CDK4/6-IN-14, has an appropriate t1/2 for both oral and intravenous administration (2.62 and 3.59 hours, respectively). Additionally, CDK4/6-IN-14 has an oral bioavailability of 43%[1]. Sprague-Dawley rats' pharmacokinetic parameters for CDK4/6-IN-14 (Compound 42)[1]. administrator. The dose is as follows: IV 290.52 372.56 3.50 0.033 2.62 PO 144.11 1612.18 9.11 6 3.59 43 Cmax (ng/mL) AUC0-∞ (h × ng/mL) MRT0-∞ (h) Tmax (h) t1/2 (h) F (%)
Cell Assay	Cell Cytotoxicity Assay[1] Cell Types: MCF-7 and T47D cells Tested Concentrations: 1 μM, 2 μM, 4 μM (T47D cells); 1.5 μM, 3 μM, 6 μM (MCF-7 cells) Incubation Duration: 5 days Experimental Results: Dramatically inhibited growth and clone formation of MCF-7 and T47D cells. Western Blot Analysis[1] Cell Types: MCF-7 and T47D cells Tested Concentrations: 1 μM, 2 μM, 4 μM (T47D cells); 1.5 μM, 3 μM, 6 μM (MCF-7 cells) Incubation Duration: 24 hrs (hours) Experimental Results: Dramatically inhibited the phosphorylation of RB.
Animal Protocol	Animal/Disease Models: BALB/c nude mice bearing MCF-7 cells[1] Doses: 100 mg/kg, 150 mg/kg Route of Administration: Orally administration; one time/day; for 23 days Experimental Results: Dramatically inhibited tumor growth of the MCF-7 xenograft model.
References	[1]. Weijiao Chen, et al. Discovery, Optimization, and Evaluation of Selective CDK4/6 Inhibitors for the Treatment of Breast Cancer. J Med Chem. 2022 Nov 24;65(22):15102-15122.

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.)