Table 9.
ADMET calculation of MCM, MCFA and reference drug
| ADMET predicted profile—classification | |||||||
|---|---|---|---|---|---|---|---|
| Model | Result | Probability | |||||
| MCM | MCFA | Caproic | Aspirin | Paracetamol | Ibuprofen | ||
| Absorption | |||||||
| Blood–brain barrier | BBB + | 0.5794 | 0.9488 | 0.9657 | 0.9376 | 0.9544 | 0.9619 |
| Human intestinal absorption | HIA + | 0.9310 | 0.9888 | 0.9867 | 0.9645 | 0.9921 | 0.9927 |
| Caco-2 permeability | Caco2- | 0.6062 | 0.8326 | 0.8092 | 0.6607 | 0.8285 | 0.8866 |
| P-glycoprotein substrate | Substrate | 0.6014 | 0.6321 | 0.6103 | 0.6850 (non) | 0.8202 (non) | 0.7590 (non) |
| P-glycoprotein inhibitor | Non-inhibitor | 0.8441 | 0.9598 | 0.9618 | 0.9118 | 0.9820 | 0.9705 |
| Non-inhibitor | 0.7798 | 0.9277 | 0.9651 | 0.9615 | 0.9781 | 0.9323 | |
| Renal organic cation transporter | Non-inhibitor | 0.9135 | 0.9266 | 0.9360 | 0.9140 | 0.9292 | 0.9323 |
| Distribution | |||||||
| Subcellular localization | Mitochondria | 0.7898 | 0.5152 | 0.5379 | 0.9369 | 0.7695 | 0.6974 |
| Metabolism | |||||||
| CYP450 2C9 Substrate | Non-substrate | 0.8889 | 0.7886 | 0.7728 | 0.7518 | 0.7259 | 0.7594 |
| CYP450 2D6 substrate | Non-substrate | 0.8304 | 0.8956 | 0.8966 | 0.9116 | 0.8918 (sub) | 0.9116 |
| CYP450 3A4 substrate | Non-substrate | 0.6858 | 0.6982 | 0.6955 | 0.7225 | 0.5554 | 0.6877 |
| CYP450 1A2 inhibitor | Non-inhibitor | 0.6657 | 0.8326 | 0.8055 (inhibitor) | 0.9046 | 0.9045 | 0.9045 |
| CYP450 2C9 inhibitor | Non-inhibitor | 0.8948 | 0.8808 | 0.8977 | 0.9071 | 0.9070 | 0.9305 |
| CYP450 2D6 inhibitor | Non-inhibitor | 0.9128 | 0.9554 | 0.9504 | 0.9576 | 0.9755 | 0.9231 |
| CYP450 2C19 inhibitor | Non-inhibitor | 0.8693 | 0.9578 | 0.9474 | 0.9445 | 0.9161 | 0.9881 |
| CYP450 3A4 inhibitor | Non-inhibitor | 0.8425 | 0.9484 | 0.9531 | 0.9611 | 0.8496 | 0.9655 |
| CYP inhibitory promiscuity | Low CYP Inhibitory Promiscuity | 0.9642 | 0.9647 | 0.9587 | 0.9557 | 0.8842 | 0.9691 |
| Excretion | |||||||
| Toxicity | |||||||
| Human ether-a-go-go-related gene inhibition | Weak inhibitor | 0.9652 | 0.9322 | 0.9515 | 0.9433 | 0.9717 | 0.9719 |
| Non-inhibitor | 0.6466 | 0.8868 | 0.8971 | 0.9799 | 0.9597 | 0.9734 | |
| AMES toxicity | Non-AMES toxic | 0.9132 | 0.9865 | 0.9850 | 0.9326 | 0.8767 | 0.9894 |
| Carcinogens | Non-carcinogens | 0.7897 | 0.6452 | 0.6359 | 0.8356 | 0.7654 | 0.5553 (carcinogen) |
| Fish toxicity | High FHMT | 0.8950 | 0.9144 | 0.7928 | 0.9391 | 0.6816 | 0.9471 |
| Tetrahymena pyriformis toxicity | High TPT | 0.9891 | 0.9990 | 0.9766 | 0.8519 | 0.6528 | 0.9961 |
| Honey bee toxicity | High HBT | 0.6262 | 0.6691 | 0.6652 | 0.7453 | 0.6871 | 0.7451 |
| Biodegradation | Ready biodegradable | 0.9480 | 0.8795 | 0.8962 | 0.9067 | 0.6342 | 0.5142 |
| Acute oral toxicity | IV | 0.6566 IV | 0.6378 IV | 0.8226 III | 0.7260 II | 0.8429 III | 0.8084 III |
| Carcinogenicity (Three-class) | Non-required | 0.7095 | 0.7057 | 0.6773 | 0.7139 | 0.4806 (warning) | 0.7313 |
| ADMET predicted profile—regression | |||||||
|---|---|---|---|---|---|---|---|
| Model | Value | Unit | |||||
| Absorption | |||||||
| Aqueous solubility | LogS | − 2.0181 | − 3.5022 | − 2.0177 | − 1.7826 | − 1.1313 | − 3.9041 |
| Caco-2 permeability | LogPapp, cm/s | 0.0083 | 1.3950 | 1.4589 | 0.5054 | 1.5175 | 1.7486 |
| Distribution | |||||||
| Metabolism | |||||||
| Excretion | |||||||
| Toxicity | |||||||
| Rat acute Toxicity | LD50, mol/kg | 0.8172 | 1.3275 | 1.6604 | 2.6386 | 1.8596 | 2.3092 |
| Fish toxicity | pLC50, mg/L | 2.5412 | 1.8920 | 2.6304 | − 0.1352 | 2.7860 | 1.3122 |
| Tetrahymena pyriformis toxicity | pIGC50, ug/L | 0.8291 | 0.3852 | − 0.3351 | 0.2236 | − 0.6949 | 1.3858 |