PF-07104091 (PF07104091) is a novel and orally bioavailable inhibitor of cyclin-dependent kinase 2 (CDK2) with potential anticancer activity. PF-07104091 exhibits selectivity against CDK1 of 100 fold, selectivity against CDK4 and CDK6 of 200 to 400 fold, selectivity against CDK9 of 170 fold, and selectivity against GSK3B of more than 500 fold. The single-agent PF-07104091 showed dose-dependent tumor growth reduction with 86 percent maximal effect in a study on tumor growth inhibition in an ovarian cancer model. It also showed single-agent efficacy in multiple ovarian models. Additionally, PF-07104091 restored cell-cycle control in cancer types unresponsive to CDK4/6 inhibitors. In a phase I/IIa dose escalation trial, PF-07104091 is presently being tested; the first patient will receive a dose in October 2020. It is possible to treat cyclinE-amplified cancers with PF-07104091. One of the many cyclin-dependent kinases, CDK2, needs to bind to a regulatory cyclin subunit, like A or E.

Physicochemical Properties

Molecular Formula	C19H28N6O4
Molecular Weight	404.463423728943
Exact Mass	404.217
Elemental Analysis	C, 56.42; H, 6.98; N, 20.78; O, 15.82
CAS #	2460249-19-6
Related CAS #	2460249-19-6
PubChem CID	154616422
Appearance	Solid powder
LogP	1.2
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	8
Heavy Atom Count	29
Complexity	577
Defined Atom Stereocenter Count	2
SMILES	CC(C)NC(=O)O[C@@H]1CC[C@@H](C1)C2=CC(=NN2)NC(=O)C3=CC(=NN3C)COC
InChi Key	MTNBRBDFNSGQKB-GXTWGEPZSA-N
InChi Code	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
Chemical Name	[(1R,3S)-3-[3-[[5-(methoxymethyl)-2-methylpyrazole-3-carbonyl]amino]-1H-pyrazol-5-yl]cyclopentyl] N-propan-2-ylcarbamate
Synonyms	tagtociclib; PF-07104091; PF-7104091; PF 07104091; PF 7104091; PF07104091; PF7104091
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	CDK2
References	[1]. Cancer Immunol Res . 2022 Apr 1;10(4):525-539.
Additional Infomation	Tagtociclib is an orally bioavailable inhibitor of cyclin-dependent kinase 2 (CDK2), with potential antineoplastic activity. Upon administration, tagtociclib selectively targets, binds to and inhibits the activity of CDK2. This may lead to cell cycle arrest, the induction of apoptosis, and the inhibition of tumor cell proliferation. CDKs are serine/threonine kinases that are important regulators of cell cycle progression and cellular proliferation and are frequently overexpressed in tumor cells. CDK2/cyclin E complex plays an important role in retinoblastoma (Rb) protein phosphorylation and the G1-S phase cell cycle transition. CDK2/cyclin A complex plays an important role in DNA synthesis in S phase and the activation of CDK1/cyclin B for the G2-M phase cell cycle transition.

Solubility Data

Solubility (In Vitro)

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

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	2.4724 mL	12.3622 mL	24.7243 mL
	5 mM	0.4945 mL	2.4724 mL	4.9449 mL
	10 mM	0.2472 mL	1.2362 mL	2.4724 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.