G140 is a potent and sensitive conjugate of GMP-AMP synthase (cGAS), with IC50s of 14.0 nM and 442 nM for h-cGAS and m-cGAS, respectively. G140 exhibits anti-inflammatory effect.

Physicochemical Properties

Molecular Formula	C17H16CL2N4O2
Molecular Weight	379.24
Exact Mass	378.065
CAS #	2369751-07-3
PubChem CID	139388865
Appearance	White to off-white solid powder
Density	1.61±0.1 g/cm3(Predicted)
Boiling Point	663.1±55.0 °C(Predicted)
LogP	2
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	2
Heavy Atom Count	25
Complexity	525
Defined Atom Stereocenter Count	0
InChi Key	NVPFAXHXXODQRO-UHFFFAOYSA-N
InChi Code	InChI=1S/C17H16Cl2N4O2/c1-22-4-2-13(21-22)9-6-11(18)16(19)17-15(9)10-7-23(14(25)8-24)5-3-12(10)20-17/h2,4,6,20,24H,3,5,7-8H2,1H3
Chemical Name	1-[6,7-dichloro-9-(1-methylpyrazol-3-yl)-1,3,4,5-tetrahydropyrido[4,3-b]indol-2-yl]-2-hydroxyethanone
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 human THP1 and primary macrophages, G140 (0.1-100 μM; 4 hours) suppresses h-cGAS in a diluted way with IC50 values of 1.70 and 0.86 μM, respectively [1]. In THP1 cells, G140 (0.1-100 μM; 24 hours) reduces cell viability with an LD50 greater than 100 μM[1].
References	[1]. Development of human cGAS-specific small-molecule inhibitors for repression of dsDNA-triggered interferon expression. Nat Commun. 2019 May 21; 10(1): 2261.

Solubility Data

Solubility (In Vitro)

DMSO : ~250 mg/mL (~659.21 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (5.48 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 20.8 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 (5.48 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 20.8 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: ≥ 2.08 mg/mL (5.48 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	2.6369 mL	13.1843 mL	26.3685 mL
	5 mM	0.5274 mL	2.6369 mL	5.2737 mL
	10 mM	0.2637 mL	1.3184 mL	2.6369 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.