Compound selectivity / Published data reanalysis
See source-derived results
Selective signaling has not established reproductive protection
Different assay states, unequal tissue responses and unmatched blood contexts remain. There is no direct DL001 reproductive-protection comparison or established healthy-human testicular-volume inference.
{
"inputs_sha256": "acffc16a75bfdbf2164db8641f816713c3a09d6cbd4250fe32837ab9fd3dc89f",
"hash_convention": "UTF-8 text after universal-newline normalization to LF",
"analysis_status": "Descriptive source reanalysis, no new significance/equivalence tests or reproductive-risk model",
"PC3_cell_selectivity": {
"rapamycin": {
"C1_ic50_pM": {
"n": 4,
"mean": 63.30875,
"sample_sd": 18.539744161755127,
"sem": 9.269872080877564
},
"C2_ic50_pM": {
"n": 4,
"mean": 534.8955,
"sample_sd": 257.4247456772561,
"sem": 128.71237283862806
},
"paired_replicate_C2_C1_selectivity": [
11.138165864518875,
16.67567071411712,
1.8753832100804584,
9.088419859381116
],
"mean_of_paired_ratios": {
"n": 4,
"mean": 9.694409912024392,
"sample_sd": 6.119009618852125,
"sem": 3.0595048094260626
},
"ratio_of_mean_ic50s": 8.448997966315872
},
"DL001": {
"C1_ic50_pM": {
"n": 4,
"mean": 74.93599999999999,
"sample_sd": 24.883770118961746,
"sem": 12.441885059480873
},
"C2_ic50_pM": {
"n": 4,
"mean": 26245.41275,
"sample_sd": 14227.642744789488,
"sem": 7113.821372394744
},
"paired_replicate_C2_C1_selectivity": [
829.2318040543676,
587.6838400281579,
94.54376231254774,
222.04815010511405
],
"mean_of_paired_ratios": {
"n": 4,
"mean": 433.37688912504683,
"sample_sd": 336.6400018476735,
"sem": 168.32000092383674
},
"ratio_of_mean_ic50s": 350.2377061759368
},
"relative_DL001_vs_rapamycin": {
"ratio_of_compound_mean_paired_selectivities": 44.70379250082162,
"ratio_of_compound_ratios_of_mean_ic50s": 41.45316492822587,
"cross_compound_replicate_pairing_assumed": false,
"new_p_value": null,
"interpretation": "Different descriptive estimands, not conflicting experiments. No reproductive or tissue selectivity follows from PC3 ratios."
}
},
"tissue_pathway_series": 18,
"tissue_pathway_interpretation": "Different tissues and source sex/context; zeros retained as normalized readouts, not proof of absent kinase activity. No parent tissue exposure is measured by these values.",
"reported_whole_blood_compound_concentration_ng_per_mL": {
"DL001": {
"n": 9,
"mean": 186.27777777777777,
"sample_sd": 34.14135241088795,
"sem": 11.380450803629316
},
"rapamycin": {
"n": 18,
"mean": 257.2055555555556,
"sample_sd": 174.50345512245082,
"sem": 41.13085881918912
}
},
"whole_blood_DL001_to_rapamycin_mean_ratio": 0.7242369915977276,
"blood_parent_exposure_qualification": "Single reported post-administration whole-blood time point, not AUC, oral F, unbound or testis concentration. Assay validation/specificity not established from the retrieved main-text methods. Cannot match to female Figure3d animals or infer cause of pathway selectivity.",
"adult_mouse_testis_mass": {
"rapamycin_to_control_reported_mean_ratio": 0.4609740670461733,
"reported_mean_difference_mg_per_pair": -85.22,
"control_n_animals": 5,
"rapamycin_n_animals": 4,
"individual_observations_or_new_confidence_interval": null,
"human_testicular_volume_inference": null,
"mechanistic_attribution_to_C2_alone": null
},
"human_transplant_descriptive_contrasts": {
"total_sperm_count_mean_difference_million": -263.59999999999997,
"motile_sperm_mean_difference_percentage_points": -18.8,
"n_semen_by_regimen": null,
"adjusted_causal_effect": null,
"probability_of_infertility_or_recovery": null,
"comparison_to_DL001": null,
"interpretation": "Unadjusted differences of reported abstract means in transplant recipients. Respondents are not the established semen sample size; no healthy-person effect or testicular-volume estimate follows."
},
"candidate_joint_evidence_gates": {
"DL001": {
"joint_human_reproductive_protection_comparison_eligible": false,
"missing": [
"testis_cell_native_parent_exposure",
"testis_cell_C1_C2_time_context",
"direct_reproductive_endpoints",
"matched_specified_intended_function",
"same_relevant_population_for_joint_comparison",
"human_reproductive_candidate_comparison"
],
"human_reproductive_risk_reduction_estimate": null
},
"rapamycin": {
"joint_human_reproductive_protection_comparison_eligible": false,
"missing": [
"testis_cell_native_parent_exposure",
"testis_cell_C1_C2_time_context",
"matched_specified_intended_function",
"same_relevant_population_for_joint_comparison",
"human_reproductive_candidate_comparison"
],
"human_reproductive_risk_reduction_estimate": null
}
},
"human_safe_analogue_or_equivalent_benefit_identified": false,
"recovery_qualification": {
"source_location": "Figure 7 and results/abstract",
"n_animals_per_group": 3,
"followup_months": 2,
"reported_outcomes": "testis mass and motility described as restored; sperm counts increased; abstract qualifies the effect as partially reversible",
"raw_individual_count_or_motility_values": null,
"numeric_recovery_probability": null,
"human_recovery_guarantee": false,
"qualification": "Do not reinterpret non-significant testis mass as demonstrated equivalence or recovery of every reproductive outcome. No figure digitization is substituted for raw data."
}
}