TDI-10229 is an orally bioactive soluble adenylyl cyclase (sAC, ADCY10) inhibitor (IC50 195 nM). TDI-10229 demonstrated nanomolar inhibition of sAC in both biochemical and cellular assays and exhibited mouse pharmacokinetic properties sufficient to warrant its use as an in vivo tool compound.

Physicochemical Properties

Molecular Formula	C16H16CLN5
Molecular Weight	313.784741401672
Exact Mass	313.109
CAS #	2810887-45-5
PubChem CID	156612922
Appearance	White to off-white solid powder
LogP	3.1
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	3
Heavy Atom Count	22
Complexity	362
Defined Atom Stereocenter Count	0
SMILES	C1(N)=NC(C2C(CC3=CC=CC=C3)=C(C)N(C)N=2)=CC(Cl)=N1
InChi Key	VSMTYSWGHKYXOF-UHFFFAOYSA-N
InChi Code	InChI=1S/C16H16ClN5/c1-10-12(8-11-6-4-3-5-7-11)15(21-22(10)2)13-9-14(17)20-16(18)19-13/h3-7,9H,8H2,1-2H3,(H2,18,19,20)
Chemical Name	4-(4-benzyl-1,5-dimethylpyrazol-3-yl)-6-chloropyrimidin-2-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

Targets	IC50: 195 nM (sAC)[2].
ln Vitro	Based on human 4-4 cells, TDI-10229 exhibits good permeability, with an IC50 of 92 nM [2].
ln Vivo	Cmax, AUC, and MRT for TDI-10229 (5 mg/kg; po) dosing were 15.5 μM, 94 μg h/mL, and 3.95 hours, respectively.
Animal Protocol	Animal/Disease Models: Mouse[2] Doses: 20 mg/kg Route of Administration: Po(pharmacokinetic/PK Analysis) Experimental Results: The Cmax, AUC and MRT were 15.5 μM, 94 μg h/mL and 3.95 hrs (hours), respectively.
References	[1]. Soluble adenylyl cyclase inhibition prevents human sperm functions essential for fertilization [published online ahead of print, 2021 Aug 31]. Mol Hum Reprod. 2021;gaab054. [2]. Discovery of TDI-10229: A Potent and Orally Bioavailable Inhibitor of Soluble Adenylyl Cyclase (sAC, ADCY10). ACS Med Chem Lett. 2021;12(8):1283-1287. Published 2021 Jul 14.

Solubility Data

Solubility (In Vitro)

DMSO: 125 mg/mL (398.37 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (6.63 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 (6.63 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	3.1869 mL	15.9347 mL	31.8695 mL
	5 mM	0.6374 mL	3.1869 mL	6.3739 mL
	10 mM	0.3187 mL	1.5935 mL	3.1869 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.