(R)-IDO/TDO-IN-1 (compound 25) is an indoleamine-2,3-dioxygenase (IDO) inhibitor (antagonist) with good pharmacokinetic properties. (R)-IDO/TDO-IN-1 displays anticancer effect in MC38 xenograft model. (R)-IDO/TDO-IN-1 is synergistic with anti-PD-1 monoclonal antibody (mAb) (SHR-1210).

Physicochemical Properties

Molecular Formula	C25H24FN5
Molecular Weight	413.489968299866
Exact Mass	413.201
CAS #	2033173-00-9
Related CAS #	IDO/TDO-IN-1;2033173-01-0
PubChem CID	122650368
Appearance	White to off-white solid powder
LogP	4
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	3
Heavy Atom Count	31
Complexity	617
Defined Atom Stereocenter Count	1
SMILES	CN1C=C(C=N1)C2=CC=C(C=C2)N3CCC(CC3)[C@@H]4C5=C(C=CC=C5F)C6=CN=CN46
InChi Key	UJGQDAMZVUNFBQ-RUZDIDTESA-N
InChi Code	InChI=1S/C25H24FN5/c1-29-15-19(13-28-29)17-5-7-20(8-6-17)30-11-9-18(10-12-30)25-24-21(3-2-4-22(24)26)23-14-27-16-31(23)25/h2-8,13-16,18,25H,9-12H2,1H3/t25-/m1/s1
Chemical Name	(5R)-6-fluoro-5-[1-[4-(1-methylpyrazol-4-yl)phenyl]piperidin-4-yl]-5H-imidazo[5,1-a]isoindole
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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.
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

References

[1]. Tu W, Yang F, Xu G, Chi J, Liu Z, Peng W, Hu B, Zhang L, Wan H, Yu N, Jin F, Hu Q, Zhang L, He F, Tao W. Discovery of Imidazoisoindole Derivatives as Highly Potent and Orally Active Indoleamine-2,3-dioxygenase Inhibitors. ACS Med Chem Lett. 2019 Jun 3;10(6):949-953.

Solubility Data

Solubility (In Vitro)

DMSO: 10 mg/mL (24.18 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1 mg/mL (2.42 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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 mg/mL (2.42 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 10.0 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: ≥ 1 mg/mL (2.42 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 10.0 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	2.4184 mL	12.0922 mL	24.1844 mL
	5 mM	0.4837 mL	2.4184 mL	4.8369 mL
	10 mM	0.2418 mL	1.2092 mL	2.4184 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.