Tagtociclib (PF-07104091) is a novel, orally bioavailable inhibitor of cyclin-dependent kinase 2 (CDK2). It exhibits high selectivity for CDK2 over other kinases, including approximately 100-fold selectivity over CDK1, 200 to 400-fold selectivity over CDK4 and CDK6, 170-fold selectivity over CDK9, and more than 500-fold selectivity over GSK3B .
Tagtociclib targets cyclin-dependent kinase 2 (CDK2), a key regulator of the cell cycle. It acts as an inhibitor, binding to CDK2 and blocking its kinase activity. CDK2 is involved in the progression of cells through the S phase of the cell cycle. By inhibiting CDK2, Tagtociclib induces cell cycle arrest and inhibits tumor cell proliferation.

Tagtociclib inhibits CDK2 activity, which is a serine/threonine kinase important for cell cycle progression. CDK2 complexes with cyclin E (regulating the G1-S phase transition and Rb phosphorylation) and cyclin A (regulating DNA synthesis in S phase and activating CDK1/cyclin B for the G2-M transition). By selectively targeting and binding to CDK2, Tagtociclib can lead to cell cycle arrest, induction of apoptosis, and inhibition of tumor cell proliferation .
In vitro, Tagtociclib is a potent inhibitor of CDK2. It shows selectivity for CDK2 over CDK1 (100-fold selectivity). The compound has potential anticancer activity in various cancer models. Specific IC50 values are not provided in the available sources.

In preclinical studies, Tagtociclib as a single agent demonstrated dose-dependent tumor growth reduction in an ovarian cancer model, with a maximal effect of 86% on tumor growth inhibition. It also showed single-agent efficacy in multiple ovarian models. Furthermore, it has been shown to restore cell-cycle control in cancer types that are unresponsive to CDK4/6 inhibitors, suggesting potential for treating cyclin E-amplified cancers .
In vivo activity data for Tagtociclib are not extensively detailed in the available sources. The compound is orally bioavailable and has shown potential antineoplastic activity in various cancer models. Specific in vivo efficacy data are not provided.

The in vitro enzyme assay for Tagtociclib involves measuring the inhibition of CDK2 kinase activity. Recombinant CDK2/cyclin complex is incubated with a substrate peptide and ATP in the presence of varying compound concentrations. The IC50 is determined by quantifying the reduction in substrate phosphorylation using techniques such as radioactive or fluorescence-based assays.

Cellular assays are performed using cancer cell lines. Cells are treated with Tagtociclib at various concentrations, and cell cycle progression is assessed by flow cytometry. Cell proliferation is measured using assays such as MTT or CellTiter-Glo. CDK2 inhibition is confirmed by assessing the phosphorylation of CDK2 substrates, such as retinoblastoma protein (Rb).

In vivo animal studies for Tagtociclib are not detailed in the available sources. The compound is orally bioavailable. Specific animal models and dosing regimens are not described.

Tagtociclib is a drug with high oral bioavailability. Its calculated LogP value is 1.2. It is soluble in DMSO (approximately 81 mg/mL) and ethanol (approximately 41 mg/mL). For optimal efficacy, it is recommended to prepare the formulation fresh before administration.
Tagtociclib is an orally bioavailable compound. This property is favorable for in vivo studies and potential therapeutic applications. Specific PK parameters such as half-life, bioavailability, and clearance are not detailed in the available sources.

Toxicity data for Tagtociclib are not reported in the available sources. As an investigational compound, it is used for research purposes only.

[1]. Cancer Immunol Res. 2022 Apr 1;10(4):525-539.

Tagtociclib is an orally bioavailable cyclin-dependent kinase 2 (CDK2) inhibitor with potential antitumor activity. After administration, Tagtociclib selectively targets, binds to, and inhibits CDK2 activity. This may lead to cell cycle arrest, induction of apoptosis, and inhibition of tumor cell proliferation. CDKs are serine/threonine kinases and important regulators of cell cycle progression and proliferation, frequently overexpressed in tumor cells. The CDK2/cyclin E complex plays a crucial role in retinoblastoma protein (Rb) phosphorylation and G1-S phase cell cycle transition. The CDK2/cyclin A complex plays a vital role in S-phase DNA synthesis and CDK1/cyclin B complex activation to initiate G2-M phase cell cycle transition. Cyclin-dependent kinase 2 (CDK2) inhibitors are commonly used to treat various solid tumors, and their main mechanisms of action are believed to include inhibiting cell proliferation, inducing cancer cell apoptosis, and inducing cell differentiation. This study found that in mouse fibrosarcoma and lung cancer models, both small molecule inhibitors and CDK2 gene knockout enhanced antitumor immunity. Mechanistically, CDK2 inhibition reduces the phosphorylation level of RB protein and E2F-mediated transcription of DNA methyltransferase 1 (DNMT1), thereby leading to increased expression of endogenous retroviral RNA and enhanced type I interferon-1 (IFN-1) response. Enhanced IFN-1 response further enhances anti-tumor immunity by promoting tumor antigen presentation and CD8+ T cell infiltration. Our study suggests that inhibiting CDK2 in cancer cells can suppress tumor growth by enhancing anti-tumor immune responses in the tumor microenvironment, suggesting a novel mechanism by which CDK2 inhibitors enhance anti-tumor immunity. [1] Tagtociclib is currently undergoing clinical trials. A phase I/IIa dose-escalation trial has been initiated, with the first patient receiving the drug in October 2020. The drug is being investigated for its potential to treat cyclin E amplified cancers and cancers resistant to CDK4/6 inhibitors.
Tagtociclib is a research compound being investigated for the treatment of cancer. It is a novel CDK2 inhibitor with oral bioavailability. The compound is available from chemical suppliers for research use only.

C19H28N6O4

404.463423728943

404.217

C, 56.42; H, 6.98; N, 20.78; O, 15.82

2460249-19-6

2460249-19-6; 2733575-91-0

154616422

Solid powder

1.2

3

6

8

29

577

2

CC(C)NC(=O)O[C@@H]1CC[C@@H](C1)C2=CC(=NN2)NC(=O)C3=CC(=NN3C)COC

MTNBRBDFNSGQKB-GXTWGEPZSA-N

InChI=1S/C19H28N6O4/c1-11(2)20-19(27)29-14-6-5-12(7-14)15-9-17(23-22-15)21-18(26)16-8-13(10-28-4)24-25(16)3/h8-9,11-12,14H,5-7,10H2,1-4H3,(H,20,27)(H2,21,22,23,26)/t12-,14+/m0/s1

[(1R,3S)-3-[3-[[5-(methoxymethyl)-2-methylpyrazole-3-carbonyl]amino]-1H-pyrazol-5-yl]cyclopentyl] N-propan-2-ylcarbamate

tagtociclib; PF-07104091; PF-7104091; PF 07104091; PF 7104091; PF07104091; PF7104091

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO: ~81 mg/mL (~200.3 mM)
Ethanol: ~41 mg/mL (~101.4 mM)

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.

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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).

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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)

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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).

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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

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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.

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 (Please use freshly prepared in vivo formulations for optimal results.)