Reverse transcriptase-IN-1 (Compound 12z), a diarylbenzopyrimidine (DABP) analogue, is a potent, orally bioactive HIV-1 non-nucleoside reverse transcriptase inhibitor. Reverse transcriptase-IN-1 has antiviral effect with EC50s of 3.4 nM, 4.3 nM and 3.6 nM against HIV-1 IIIB, E138K and K103N mutants respectively, and the IC50 against HIV-1 reverse transcriptase is 13.7 nM. .

Physicochemical Properties

Molecular Formula	C25H17N7O2
Molecular Weight	447.45
Exact Mass	447.144
CAS #	2380001-43-2
PubChem CID	139600333
Appearance	Light yellow to yellow solid powder
Density	1.4±0.1 g/cm3
Boiling Point	708.3±70.0 °C at 760 mmHg
Flash Point	382.1±35.7 °C
Vapour Pressure	0.0±2.3 mmHg at 25°C
Index of Refraction	1.729
LogP	4.56
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	8
Rotatable Bond Count	5
Heavy Atom Count	34
Complexity	831
Defined Atom Stereocenter Count	0
SMILES	C1(=C(NC2=NC(NC3C=CC(=CC=3)C#N)=NC3C2=CC=CC=3)C(C)=CC(=C1)/C=C/C#N)[N+]([O-])=O
InChi Key	MNZKGXAFXCQSCG-SNAWJCMRSA-N
InChi Code	InChI=1S/C25H17N7O2/c1-16-13-18(5-4-12-26)14-22(32(33)34)23(16)30-24-20-6-2-3-7-21(20)29-25(31-24)28-19-10-8-17(15-27)9-11-19/h2-11,13-14H,1H3,(H2,28,29,30,31)/b5-4+
Chemical Name	4-[[4-[4-[(E)-2-cyanoethenyl]-2-methyl-6-nitroanilino]quinazolin-2-yl]amino]benzonitrile
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	HIV-1
ln Vivo	Reverse transcriptase-IN-1 (Compound 12z) has a markedly increased oral bioavailability of 16.5% in rats when administered at a dose of 5 mg/kg. Reverse transcriptase-IN-1 has an inherent microsome clearance of 33.2 μL/min/mg proteins in rats. Reverse transcriptase-IN-1 is absorbed at two different doses, with mean residence times (MRTs) of 11.8 hours (5 mg/kg, po) and 11.4 hours (1 mg/kg, iv), according to the PK study and safety evaluation. At a dose of 5 mg/kg, the Cmax of reverse transcriptase-IN-1 is 39.9 ng/mL. Rats used in a single-dose toxicity test for reverse transcriptase-IN-1 exhibit no signs of death, and the animals' body weight did not drop abnormally in the week after an intragastrical dose of 293 mg/kg body weight. According to the aforementioned findings, reverse transcriptase-IN-1 may be a viable oral bioavailable option for studying HIV-1 infection in humans[1].
References	[1]. Han S, et al. Molecular Hybridization-Inspired Optimization of Diarylbenzopyrimidines as HIV-1 Nonnucleoside Reverse Transcriptase Inhibitors with Improved Activity against K103N and E138K Mutants and Pharmacokinetic Profiles. ACS Infect Dis. 2019 Oct 24.

Solubility Data

Solubility (In Vitro)

DMSO : 12.5 mg/mL (27.94 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.25 mg/mL (2.79 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 12.5 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: 1.25 mg/mL (2.79 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 12.5 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2349 mL	11.1744 mL	22.3489 mL
	5 mM	0.4470 mL	2.2349 mL	4.4698 mL
	10 mM	0.2235 mL	1.1174 mL	2.2349 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.