(3S, 4S)-PF-06459988 is the less active S-enantiomer of PF-06459988. PF-06459988 is a potent, irreversible inhibitor of the T790M mutant epidermal growth factor receptor (EGFR). PF-06459988 has excellent selectivity for EGFR wild-type while having the least reactive electrophile, reducing the tendency of off-target labeling.

Physicochemical Properties

Molecular Formula	C19H22CLN7O3
Molecular Weight	431.88
Exact Mass	431.147
CAS #	1858291-14-1
Related CAS #	PF-06459988;1428774-45-1
PubChem CID	127030086
Appearance	Light yellow to yellow solid powder
LogP	1.8
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	7
Heavy Atom Count	30
Complexity	629
Defined Atom Stereocenter Count	2
SMILES	CN1C=C(C=N1)NC2=NC3=C(C(=CN3)Cl)C(=N2)OC[C@@H]4CN(C[C@H]4OC)C(=O)C=C
InChi Key	ODMXWZROLKITMS-SMDDNHRTSA-N
InChi Code	InChI=1S/C19H22ClN7O3/c1-4-15(28)27-7-11(14(9-27)29-3)10-30-18-16-13(20)6-21-17(16)24-19(25-18)23-12-5-22-26(2)8-12/h4-6,8,11,14H,1,7,9-10H2,2-3H3,(H2,21,23,24,25)/t11-,14+/m0/s1
Chemical Name	1-[(3S,4S)-3-[[5-chloro-2-[(1-methylpyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxymethyl]-4-methoxypyrrolidin-1-yl]prop-2-en-1-one
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	EGFR[1]
References	[1]. Cheng, H., et al. Discovery of 1-{(3R,4R)-3-[({5-Chloro-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)methyl]-4-methoxypyrrolidin-1-yl}prop-2-en-1-one (PF-06459988), a Potent, WT Sparing, Irreversible Inhibitor of T790M-Containing EGFR Mutants. Journal of Medicinal Chemistry, 59(5), 2005–2024.

Solubility Data

Solubility (In Vitro)

DMSO: 50 mg/mL (115.77 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.79 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: ≥ 2.5 mg/mL (5.79 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. 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.3155 mL	11.5773 mL	23.1546 mL
	5 mM	0.4631 mL	2.3155 mL	4.6309 mL
	10 mM	0.2315 mL	1.1577 mL	2.3155 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.