| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
CDK2/cyclin E1 1.16 nM (Ki) GSK3β 537.81 nM (Ki); 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 .
CDK2/cyclin E1 (with a Ki of 1.16 nM) and GSK3beta (with a Ki of 537.81 nM). Tagtociclib hydrate also inhibits CDK1/cyclin A2 (Ki=110 nM), CDK4/cyclin D1 (Ki=238 nM), CDK6/cyclin D3 (Ki=465 nM), and CDK9 (Ki=117 nM). |
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| ln Vitro |
PF-07104091 hydrate (Example 13) inhibits CDK1/cyclin A2, CDK4/cyclin D1, CDK6/cyclin D3 and CDK9, with Kis of 110, 238, 465 and 117 nM, respectively[1].
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 cell‑free kinase assays, Tagtociclib hydrate shows high selectivity for CDK2/cyclin E1 with a Ki of 1.16 nM. It also inhibits GSK3beta with a Ki of 537.81 nM and shows moderate activity against CDK1, CDK4, CDK6, and CDK9. In cyclin E1‑amplified cancer cells, it induces G1 arrest and reduces the phosphorylation of retinoblastoma protein (pRb). |
| ln Vivo |
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 .
A general cell‑free protocol for CDK2 kinase inhibition: A radiometric or time‑resolved fluorescence resonance energy transfer (TR‑FRET) assay is used. Recombinant active human CDK2/cyclin E1 complex (5‑10 nM) is incubated with a biotinylated retinoblastoma protein‑derived peptide substrate (1 uM) in kinase buffer (25 mM HEPES, pH 7.5, 10 mM MgCl2, 1 mM DTT, 0.01% Tween‑20) containing 10 uM ATP. Varying concentrations of Tagtociclib hydrate (0.01 nM to 10 uM) are added. After 30‑60 minutes at 30degC, the reaction is stopped with EDTA. Phosphorylated peptide is detected using an anti‑phospho‑pRb (Ser780) antibody labeled with a donor fluorophore and streptavidin‑labeled acceptor (XL665). The IC₅0 is calculated. |
| Enzyme Assay |
A general cellular protocol for CDK2 inhibitors: Cyclin E1‑amplified cancer cells (e.g., OVCAR3, HCC70, or other sensitive cell lines) are seeded in 96‑well plates. Cells are treated with serial dilutions of Tagtociclib hydrate (0.1 nM to 10 uM) for 72‑120 hours. Cell viability is measured using CellTiter‑Glo or MTT assay to determine the IC₅0. For cell cycle analysis, cells are treated for 24‑48 hours, fixed, stained with propidium iodide, and analyzed by flow cytometry. For pRb phosphorylation assessment, cells are treated for 6‑24 hours, lysed, and subjected to Western blot with anti‑pRb (Ser780) antibody.
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| Cell Assay |
G1/S inhibition is measured by 5‑ethynyl‑2′‑deoxyuridine (EdU) incorporation assay.
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| Animal Protocol |
A general animal protocol for Tagtociclib hydrate: Female NOD/SCID mice are subcutaneously implanted with cyclin E1‑amplified patient‑derived xenograft (PDX) tumors (e.g., OV‑65‑P ovarian cancer PDX). When tumors reach ~150‑200 mm3, mice are randomized into treatment groups (n=8‑10/group). Tagtociclib hydrate is formulated in a suitable vehicle (e.g., 0.5% methylcellulose or 10% DMSO, 40% PEG300, 5% Tween‑80, 45% saline) and administered via oral gavage at doses of 10, 30, and 100 mg/kg once daily for 21 days. Tumor volume is measured twice weekly. At study end, tumors are harvested for Western blot (pRb, cyclin D1, Ki‑67), IHC, and TUNEL staining.
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| ADME/Pharmacokinetics |
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.
General PK protocol for Tagtociclib hydrate: Male Sprague‑Dawley rats are administered the compound via oral gavage (PO, 10 mg/kg) and intravenous (IV, 2 mg/kg). Blood samples are collected at 0.083, 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours post‑dose. Plasma concentrations are quantified by LC‑MS/MS. PK parameters (Cmax, Tmax, AUC, t½, clearance, Vd, and oral bioavailability) are calculated. The compound is predicted to have moderate to good oral bioavailability. |
| Toxicity/Toxicokinetics |
General toxicity protocol for Tagtociclib hydrate: A 14‑day repeat‑dose oral toxicity study is performed in ICR mice. The compound is administered via oral gavage at doses of 10, 30, and 100 mg/kg/day for 14 days. Parameters include clinical signs, body weight, food consumption, hematology (complete blood count, platelet count), serum chemistry (ALT, AST, BUN, creatinine), and histopathology of the bone marrow, gastrointestinal tract, and testes. Special attention is paid to myelosuppression (neutropenia, thrombocytopenia), which is an on‑target effect of CDK2 inhibition.
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| References | |
| Additional Infomation |
Tagtociclib is currently under clinical investigation. A Phase I/IIa dose-escalation trial has been initiated, with the first patient receiving treatment in October 2020. The drug is being investigated for the treatment of cancers with cyclin E amplification and cancers resistant to CDK4/6 inhibitors.
Tagtociclib hydrate (PF‑07104091) is being developed by Pfizer. A Phase 1/2a first‑in‑human clinical trial (NCT04803526) is evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of PF‑07104091 (Tagtociclib) as monotherapy and in combination with other therapies. The molecular formula is C1₉H30N₆O₅, and the molecular weight is 422.48 g/mol. The IUPAC name is (1R,3S)-3-(3-(3-(methoxymethyl)-1-methyl-1H-pyrazole-5-carboxamido)-1H-pyrazol-5-yl)cyclopentyl isopropylcarbamate hydrate. |
| Molecular Formula |
C19H30N6O5
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|---|---|
| Molecular Weight |
422.478703975677
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| Exact Mass |
404.47
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| CAS # |
2733575-91-0
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| Related CAS # |
2460249-19-6; 2733575-91-0
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| PubChem CID |
154616421
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| Appearance |
Solid powder
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
30
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| Complexity |
577
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O.COCC1C=C(C(NC2C=C([C@@H]3C[C@H](OC(NC(C)C)=O)CC3)NN=2)=O)N(C)N=1
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| InChi Key |
CFGMPDNYFGKCIR-DSHXVJGRSA-N
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| InChi Code |
InChI=1S/C19H28N6O4.H2O/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);1H2/t12-,14+;/m0./s1
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| Chemical Name |
[(1R,3S)-3-[3-[[3-(methoxymethyl)-1-methylpyrazole-5-carbonyl]amino]-1H-pyrazol-5-yl]cyclopentyl] N-propan-2-ylcarbamate;hydrate
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| Synonyms |
Tagtociclib (hydrate); Tagtociclib monohydrate; 2733575-91-0; (1R,3S)-3-[3-(y([3-(Methoxymethyl)-1-methyl-1H-pyrazol-5-yl]carbonyl)amino)-1H-pyrazol-5-yl]cyclopentyl propan-2-ylcarbamate monohydrate; Tagtociclib hydrate; PF-07104091 hydrate
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| HS Tariff Code |
2934.99.9001
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| 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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : 200 mg/mL (473.40 mM; with sonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (11.83 mM)(saturation unknown) in 10% DMSO 40% PEG300 5% Tween-80 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution This solution produces a clear solution of ≥ 5 mg/mL (saturation unknown).
For example, if 1 mL of working solution, add 100 μL of 50.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix well; then add 50 μL Tween-80 to the above system and mix well; then add 450 μL saline to make up to 1 mL. *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5 mg/mL (11.83 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 This protocol will produce a clear solution of ≥ 5 mg/mL (saturation unknown). . For example, if 1 mL of working solution, add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD in saline and mix. *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. Solubility in Formulation 3: ≥ 5 mg/mL (11.83 mM)(saturation unknown) in 10% DMSO 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution, add 100 μL of 50.0 mg/mL clear DMSO stock solution to 900 μL corn oil and mix well. Take μL of DMSO stock solution and add μL. μL, mix well until clear, add μL Tween 80, mix well until clear, and add μL normal saline. Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear and transparent normal saline solution. If the continuous administration period exceeds half a month, please choose this solution with caution. Please ensure that the first step stock solution is dissolved to a clear state, and add co-solvents from left to right. You can use ultrasonic heating (ultrasonic cleaning instrument, recommended frequency 20-40 kHz), vortex blowing and other methods to assist dissolution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3670 mL | 11.8349 mL | 23.6698 mL | |
| 5 mM | 0.4734 mL | 2.3670 mL | 4.7340 mL | |
| 10 mM | 0.2367 mL | 1.1835 mL | 2.3670 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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