TTP-8307 is a novel and highly potent inhibitor of the replication of several rhino- and enteroviruses. TTP-8307 inhibits coxsackievirus B3 (CVB3; EC50=1.2 μM) and poliovirus by interfering with the synthesis of viral RNA. TTP-8307 exerts antiviral activity through oxysterol-binding protein (OSBP).

Physicochemical Properties

Molecular Formula	C27H21FN4O
Molecular Weight	436.480249166489
Exact Mass	436.169
CAS #	950225-08-8
PubChem CID	16739062
Appearance	White to light yellow solid powder
LogP	4.9
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	5
Heavy Atom Count	33
Complexity	654
Defined Atom Stereocenter Count	1
SMILES	C(C1C=CC=C(C2=CN=C(C3N=CC4C=CC=CC=4C=3)N2)C=1)(=O)N[C@@H](C1C=CC(F)=CC=1)C
InChi Key	SIBDJDZVNXVLEX-QGZVFWFLSA-N
InChi Code	InChI=1S/C27H21FN4O/c1-17(18-9-11-23(28)12-10-18)31-27(33)21-8-4-7-20(13-21)25-16-30-26(32-25)24-14-19-5-2-3-6-22(19)15-29-24/h2-17H,1H3,(H,30,32)(H,31,33)/t17-/m1/s1
Chemical Name	N-[(1R)-1-(4-fluorophenyl)ethyl]-3-(2-isoquinolin-3-yl-1H-imidazol-5-yl)benzamide
Synonyms	TTP-8307TTP 8307TTP8307
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

TTP-8307 inhibits coxsackievirus B3 (CVB3 Nancy) replication with an EC50 of 1.2 μM, targeting non-structural protein 3A. Coxsackievirus B3, three poliovirus Sabin strains, and coxsackieviruses A16 and A21 (EC50 of 0.85 and 5.34 μM) are all inhibited by TTP-8307. Human rhinoviruses (HRV) 2, 29, 39, 45, 63, and 85 are inhibited by TTP-8307. Entovirus replication inhibitor TTP-8307 is resistant to mutations in nonstructural protein 3A [1]. The OSBP-dependent viruses HCV and encephalomyocarditis virus (EMCV) are inhibited by TTP-8307[2].

References

[1]. Mutations in the nonstructural protein 3A confer resistance to the novel enterovirus replication inhibitor TTP-8307. Antimicrob Agents Chemother. 2009 May;53(5):1850-7. [2]. Uncovering oxysterol-binding protein (OSBP) as a target of the anti-enteroviral compound TTP-8307. Antiviral Res. 2017 Apr;140:37-44.

Solubility Data

Solubility (In Vitro)

DMSO : ~100 mg/mL (~229.11 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.5 mg/mL (5.73 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. 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 (5.73 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 (5.73 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	2.2911 mL	11.4553 mL	22.9106 mL
	5 mM	0.4582 mL	2.2911 mL	4.5821 mL
	10 mM	0.2291 mL	1.1455 mL	2.2911 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.