Contrera, Joseph F. published the artcileEstimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose, Computed Properties of 40180-04-9, the main research area is QSAR structure activity relationship mol modeling drug screening.
Estimating the maximum recommended starting dose (MRSD) of a pharmaceutical for phase I human clin. trials and the no observed effect level (NOEL) for non-pharmaceuticals is currently based exclusively on an extrapolation of the results of animal toxicity studies. This process is inexact and requires the results of toxicity studies in multiple species (rat, dog, and monkey) to identify the no observed adverse effect level (NOAEL) and most sensitive test species. Multiple uncertainty (safety) factors are also necessary to compensate for incompatibility and uncertainty underlying the extrapolation of animal toxicity to humans. The maximum recommended daily dose for pharmaceuticals (MRDD) is empirically derived from human clin. trials. The MRDD is an estimated upper dose limit beyond which a drug’s efficacy is not increased and/or undesirable adverse effects begin to outweigh beneficial effects. The MRDD is essentially equivalent to the NOAEL in humans, a dose beyond which adverse (toxicol.) or undesirable pharmacol. effects are observed The NOAEL in test animals is currently used to estimate the safe starting dose in human clin. trials. MDL QSAR predictive modeling of the human MRDD may provide a better, simpler and more relevant estimation of the MRSD for pharmaceuticals and the toxic dose threshold of chems. in humans than current animal extrapolation based risk assessment models and may be a useful addition to current methods. A database of the MRDD for over 1300 pharmaceuticals was compiled and modeled using MDL QSAR software and E-state and connectivity topol. descriptors. MDL QSAR MRDD models were found to have good predictive performance with 74-78% of predicted MRDD values for 120 internal and 160 external validation compounds falling within a range of ±10-fold the actual MRDD value. The predicted MRDD can be used to estimate the MRSD for pharmaceuticals in phase I clin. trials with the addition of a 10-fold safety factor. For non-pharmaceutical chems. any compound-related effect can be considered an undesirable and adverse toxicol. effect and the predicted MRDD can be used to estimate the NOEL with the addition of an appropriate safety factor.
Regulatory Toxicology and Pharmacology published new progress about Clinical trials. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Computed Properties of 40180-04-9.
Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem