PF-06952229 is a potent, selective and oral TGFbR1 inhibitor. PF-06952229 specifically binds to TGFbR1 and blocks TGFbR1-mediated signal transduction. PF-06952229 is a promising anticancer agent mainly used to study solid tumors, especially metastatic breast cancer.

Physicochemical Properties

Molecular Formula	C23H24CLFN4O3
Molecular Weight	458.913067817688
Exact Mass	458.152
CAS #	1801333-55-0
PubChem CID	118211239
Appearance	White to off-white solid powder
LogP	3.4
Hydrogen Bond Donor Count	4
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	8
Heavy Atom Count	32
Complexity	598
Defined Atom Stereocenter Count	0
SMILES	ClC1=CC=C(C(=C1)C1=CC(=C(C=N1)C(C)C)NC1C=CN=CC=1C(NC(CO)CO)=O)F
InChi Key	IPBLCOKXDQHSQW-UHFFFAOYSA-N
InChi Code	InChI=1S/C23H24ClFN4O3/c1-13(2)17-10-27-21(16-7-14(24)3-4-19(16)25)8-22(17)29-20-5-6-26-9-18(20)23(32)28-15(11-30)12-31/h3-10,13,15,30-31H,11-12H2,1-2H3,(H,28,32)(H,26,27,29)
Chemical Name	4-[[2-(5-chloro-2-fluorophenyl)-5-propan-2-ylpyridin-4-yl]amino]-N-(1,3-dihydroxypropan-2-yl)pyridine-3-carboxamide
Synonyms	PF06952229 PF 06952229
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 Vivo	In the MCF7 ER+ xenograft breast cancer tumor model, PF-06952229 (oral gavage; 30 mg/kg; twice daily; 21 days) paired with palbociclib for 21 days increases pSMAD2 suppression. Comparing this combination to PF-06952229 monotherapy, survival was likewise markedly increased [1].
Animal Protocol	Animal/Disease Models: MCF-7 ER+ HER2-xenograft breast cancer tumor model [1] Doses: 30 mg/kg Route of Administration: po (oral gavage); twice (two times) daily; 44 days Experimental Results: Tumor growth inhibition when combined with Palbociclib Enhance.
References	[1]. Combinations of tgfb inhibitors and cdk inhibitors for the treatment of breast cancer. Patent WO2020058820A1.
Additional Infomation	TGF-beta Receptor 1 Inhibitor PF-06952229 is an orally bioavailable inhibitor of transforming growth factor-beta receptor 1 (TGFbR1), with potential antineoplastic activity. Upon administration, TGF-betaR1 inhibitor PF-06952229 specifically targets and binds to TGFbR1, which prevents TGFbR1-mediated signal transduction. This abrogates TGFbR1-mediated immunosuppression, enhances anti-tumor immunity in the tumor microenvironment (TME) and promotes a cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells leading to tumor cell death. This may lead to a reduction in TGFbR1-dependent proliferation of cancer cells. The TGFb signaling pathway is often deregulated in tumors and plays a key role in the regulation of cell growth, differentiation, apoptosis, motility, invasion, and angiogenesis. It plays a key role in immunosuppression in the TME.

Solubility Data

Solubility (In Vitro)

DMSO : ~50 mg/mL (~108.95 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.45 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume 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: ≥ 2.08 mg/mL (4.53 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 is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1791 mL	10.8954 mL	21.7908 mL
	5 mM	0.4358 mL	2.1791 mL	4.3582 mL
	10 mM	0.2179 mL	1.0895 mL	2.1791 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.