PF-06928215 (PF06928215) is a novel, potent, high affinity and selective cGAS (cyclic GMP-AMP Synthase) inhibitor with the potential to be used for autoimmune diseases and inflammatory conditions. It inhibits cGAS with an IC50 of 4.9 μΜ. PF-06928215 is a high affinity (KD = 200 nM) active site-targeting, substrate-competitive cyclic GMP-AMP synthase (cGAS) inhibitor (IC50 = 4.9 μM; in the presence of 1 mM ATP, 0.3 mM GTP, 100 nM 45-bp interferon-stimulatory dsDNA (ISD)). PF-06928215 displays no inhibitory potency against dsDNA-induced IFN-β expression in cellular cGAS assays, most likely due to limited cell-permeability and/or high levels of cellular ATP and GTP in the reporter cells employed.

Physicochemical Properties

Molecular Formula	C20H20N4O4
Molecular Weight	380.3972
Exact Mass	380.148
CAS #	2378173-15-8
PubChem CID	137300622
Appearance	White to off-white solid powder
Density	1.5±0.1 g/cm3
Index of Refraction	1.725
LogP	3.19
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	4
Heavy Atom Count	28
Complexity	779
Defined Atom Stereocenter Count	2
SMILES	C1CC[C@@H]([C@@H](C1)C(=O)O)NC(=O)C2=CNN3C2=NC(=CC3=O)C4=CC=CC=C4
InChi Key	WGQGCLHXUPGUSZ-HIFRSBDPSA-N
InChi Code	InChI=1S/C20H20N4O4/c25-17-10-16(12-6-2-1-3-7-12)22-18-14(11-21-24(17)18)19(26)23-15-9-5-4-8-13(15)20(27)28/h1-3,6-7,10-11,13,15,21H,4-5,8-9H2,(H,23,26)(H,27,28)/t13-,15+/m1/s1
Chemical Name	(1R,2S)-2-[(7-oxo-5-phenyl-1H-pyrazolo[1,5-a]pyrimidine-3-carbonyl)amino]cyclohexane-1-carboxylic acid
Synonyms	PF-06928215;PF 06928215;PF06928215
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 Vitro	In the cellular cGAS experiment assessing dsDNA-induced IFN-β production, PF-06928215 did not exhibit any action [1].
References	[1]. Discovery of PF-06928215 as a high affinity inhibitor of cGAS enabled by a novel fluorescence polarization assay. PLoS One. 2017 Sep 21;12(9):e0184843.

Solubility Data

Solubility (In Vitro)

DMSO : ~33.33 mg/mL (~87.62 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.43 mg/mL (3.76 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 14.3 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: ≥ 1.43 mg/mL (3.76 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 14.3 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. Solubility in Formulation 3: ≥ 1.43 mg/mL (3.76 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 14.3 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	2.6288 mL	13.1441 mL	26.2881 mL
	5 mM	0.5258 mL	2.6288 mL	5.2576 mL
	10 mM	0.2629 mL	1.3144 mL	2.6288 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.