BI-224436, an investigational new drug under development for the treatment of HIV infection, is the first non-catalytic site integrase inhibitor (NCINI) with EC50 values of less than 15 nM against different HIV-1 laboratory strains.. It inhibits HIV replication via binding to a conserved allosteric pocket of the HIV integrase enzyme. This makes the drug distinct in mechanism of action compared to raltegravir and elvitegravir, which bind at the catalytic site.
Physicochemical Properties
| Molecular Formula | C27H26N2O4 |
| Molecular Weight | 442.506 |
| Exact Mass | 442.189 |
| CAS # | 1155419-89-8 |
| Related CAS # | 1155419-89-8; |
| PubChem CID | 66561902 |
| Appearance | White to yellow solid powder |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 631.8±55.0 °C at 760 mmHg |
| Flash Point | 335.9±31.5 °C |
| Vapour Pressure | 0.0±1.9 mmHg at 25°C |
| Index of Refraction | 1.661 |
| LogP | 4.11 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 33 |
| Complexity | 709 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | CC1=NC2=CC=CC=C2C(=C1[C@@H](C(=O)O)OC(C)(C)C)C3=C4C5=C(C=C3)OCCC5=CC=N4 |
| InChi Key | DMWVBLFYARRIDL-QFIPXVFZSA-N |
| InChi Code | InChI=1S/C24H25NO4/c1-24(2,3)29-22(23(26)27)18-14-25-19-9-5-4-8-17(19)21(18)16-10-11-20-15(13-16)7-6-12-28-20/h4-5,8-11,13-14,22H,6-7,12H2,1-3H3,(H,26,27)/t22-/m0/s1 |
| Chemical Name | (2S)-[4-(3,4-Dihydro-2H-chromen-6-yl)-3-quinolinyl][(2-methyl-2-propanyl)oxy]acetic acid |
| Synonyms | BI-224436; BI 224436; BI224436. |
| 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: This product is not stable in solution, please use freshly prepared working solution for optimal results. |
| 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 | BI 224436 has cytotoxicity more than 90 μM. BI 224436 lost 2.1 times its antiviral efficacy when 50% human serum was present. When it comes to recombinant viruses that encode the INSTI-resistant mutations N155S, Q148H, and E92Q, BI 224436 maintains its complete antiviral efficacy. In combination with the majority of licensed antiretroviral medications, including INSTIs, BI 224436 has synergistic effects. In vitro absorption, distribution, metabolism, and excretion (ADME) characteristics of BI 224436 are similar to those of drugs, and these qualities include low cytochrome P450 inhibition, solubility, and Caco-2 cell permeability [1]. |
| ln Vivo | BI 224436 in dogs (CL, 8%; F, 81%), monkeys (CL, 23%; F, 82%), and rats (percent clearance from hepatic flow [CL], 0.7%; bioavailability [F], 54%) [1]. |
| References |
[1]. Preclinical profile of BI 224436, a novel HIV-1 non-catalytic-site integrase inhibitor. Antimicrob Agents Chemother. 2014 Jun;58(6):3233-44. |
Solubility Data
| Solubility (In Vitro) | DMSO : ≥ 50 mg/mL (~112.99 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.65 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 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 (5.65 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 (5.65 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 | 2.2598 mL | 11.2992 mL | 22.5984 mL | |
| 5 mM | 0.4520 mL | 2.2598 mL | 4.5197 mL | |
| 10 mM | 0.2260 mL | 1.1299 mL | 2.2598 mL |