TH10785 is an activator of DNA glycosylase 1 (OGG1). TH10785 can interact with the phenylalanine-319 and glycine-42 amino acid (AA)s of OGG1 to increase the enzyme activity and produce the enzymatic functions of β and δ lyase. TH10785 provides molecular structural control of nitrogen base-mediated catalytic activity. TH10785 may be utilized to study a variety of diseases and aging related to oxidative damage to DNA.

Physicochemical Properties

Molecular Formula	C17H21N3
Molecular Weight	267.37
Exact Mass	267.173
CAS #	1002801-51-5
PubChem CID	8078523
Appearance	White to off-white solid powder
LogP	4.2
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	3
Heavy Atom Count	20
Complexity	322
Defined Atom Stereocenter Count	0
SMILES	N1=C2C(C=CC=C2)=C(NC2CCCCC2)N=C1C1CC1
InChi Key	ZQMGQZOHIDOPCQ-UHFFFAOYSA-N
InChi Code	InChI=1S/C17H21N3/c1-2-6-13(7-3-1)18-17-14-8-4-5-9-15(14)19-16(20-17)12-10-11-12/h4-5,8-9,12-13H,1-3,6-7,10-11H2,(H,18,19,20)
Chemical Name	N-cyclohexyl-2-cyclopropylquinazolin-4-amine
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	AP sites can become new substrates when TH10785 (6.25 μM, 30 min) induces de novo β,δ-elimination in vitro [1]. By targeting AP sites, TH10785 (10 μM, 0–2 minutes) enables OGG1 to improve DNA repair [1]. TH10785 (0–20 μM, 72 hours) causes cells to become dependent on PNKP1 and activates OGG1 β and δ-lyase [1]. When an AP site analog containing double-stranded DNA (KD=1.3 μM) is added, the affinity of TH10785 (2 μM) for OGG1 (KD=5.5 μM) increases [1].
Cell Assay	Cell Viability Assay[1] Cell Types: U2OS Cell Tested Concentrations: 0-20 μM Incubation Duration: 72 hrs (hours) Experimental Results: Reduction by combination of TH10785 and PNKP1 inhibition. Western Blot Analysis[1] Cell Types: U2OS Cell Tested Concentrations: 0.65 μM; 10 μM Incubation Duration: 30 minutes; 24 hrs (hours) Experimental Results: In the presence of TH10785, combined PNKP1 inhibition and OGG1 inhibition of AP sites via β, δ-elimination APE1-independent de novo β, δ-elimination causes upregulation of DDR members. RT-PCR[1] Cell Types: U2OS Cell Tested Concentrations: 10 μM Incubation Duration: 1 hour Experimental Results: diminished oxidative damage in guanine-rich regions of the genome. Immunofluorescence[1] Cell Types: U2OS OGG1-GFP Cell Tested Concentrations: 1 μM Incubation Duration: 0-2 minutes Experimental Results: More OGG1 is recruited at the laser injury site.
References	[1]. Small-molecule activation of OGG1 increases oxidative DNA damage repair by gaining a new function. Science. 2022 Jun 24;376(6600):1471-1476.

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 100 mg/mL (~374.01 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (9.35 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), suspension 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 (9.35 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (9.35 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 25.0 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	3.7401 mL	18.7007 mL	37.4014 mL
	5 mM	0.7480 mL	3.7401 mL	7.4803 mL
	10 mM	0.3740 mL	1.8701 mL	3.7401 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.