{ "version": { "version": "phase5-1.0.0", "date": "2026-10-26", "frozen_database_sha256": "0c53107a39e222b48611302b21fda5fb4ed50b190b6b39d41423ccc5ca5958f6", "chemical_identities": 148, "profiles": 163, "relevant_profiles": 132, "preparations": 30, "observations": 80, "frozen_observations": 46, "new_observations": 34, "bioactivity_only_profiles": 21, "exact_PWWP_structural_profiles": 130, "verified_depictions": 139, "reconciled_duplicate_rows": 0, "candidate_records": 150, "curated_scope": "Documented targeted snapshot; not an exhaustive inventory of all literature compounds. 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not an experimental measurement", "files": { "dark": "9cae4a78dcd33a27aa30-dark.svg", "light": "9cae4a78dcd33a27aa30-light.svg" }, "rdkit_version": "2025.09.3", "status": "verified_smiles_full_inchikey_match" }, "development_status": "Not independently curated", "domain_ids": [ "UP:Q7Z4V5:PWWP1" ], "entity_kind": "chemical_identity", "genes": [ "HDGFL2" ], "has_bioactivity_only": false, "has_source_conflict": false, "identity": { "aliases": [ "VARENICLINE" ], "ccd_ids": [ "QMR" ], "ccd_names": "[\"VARENICLINE\"]", "ccd_types": "[\"non-polymer\"]", "chemical_id": "INCHIKEY:JQSHBVHOMNKWFT-DTORHVGOSA-N", "connectivity_block": "JQSHBVHOMNKWFT", "curated_source_sha256": null, "curation_version": "frozen-v1.2", "external_identifiers": {}, "formal_charge_by_ccd": "{\"QMR\": 0}", "formulae": "[\"C13 H13 N3\"]", "geometry_note": "CCD ideal SDF is a reference chemical geometry, not a deposited bound pose.", "identity_status": "complete_deposited_InChIKey", "inchikey": "JQSHBVHOMNKWFT-DTORHVGOSA-N", "inventory_origin": "v1_CCD_inventory", "isomeric_smiles": "c1cnc2cc3c(cc2n1)[C@@H]4C[C@H]3CNC4", "primary_name": "VARENICLINE", "retrieval_date": "2026-10-24", "smiles_stereo_by_ccd": "{\"QMR\": \"c1cnc2cc3c(cc2n1)[C@@H]4C[C@H]3CNC4\"}", "source_metadata_sha256": "{\"QMR\": \"0439a1f642c76ab4c22ef3c5263fd2b3dec2301d7a686de21385d3defd3e9814\"}", "source_urls": [ "https://www.rcsb.org/ligand/QMR" ] }, "identity_note": "Complete deposited identity retained; no connectivity-only or name-only merge.", "identity_resolved": true, "is_control": false, "is_probe": false, "measured_observation_count": 2, "name": "varenicline", "negative_count": 0, "observation_ids": [ "PWWP:ASSAY:0010", "PWWP5:ASSAY:0027" ], "pdb_structure_count": 1, "preparation_count": 1, "preparation_ids": [ "PREP:VARENICLINE" ], "protein_ids": [ "UP:Q7Z4V5" ], "relationships": [], "relevant": true, "search_text": "varenicline inchikey:jqshbvhomnkwft-dtorhvgosa-n varenicline varenicline hdgfl2 up:q7z4v5:pwwp1 8z6o {\"aliases\":[\"varenicline\"],\"ccd_ids\":[\"qmr\"],\"ccd_names\":\"[\\\"varenicline\\\"]\",\"ccd_types\":\"[\\\"non-polymer\\\"]\",\"chemical_id\":\"inchikey:jqshbvhomnkwft-dtorhvgosa-n\",\"connectivity_block\":\"jqshbvhomnkwft\",\"curated_source_sha256\":null,\"curation_version\":\"frozen-v1.2\",\"external_identifiers\":{},\"formal_charge_by_ccd\":\"{\\\"qmr\\\": 0}\",\"formulae\":\"[\\\"c13 h13 n3\\\"]\",\"geometry_note\":\"ccd ideal sdf is a reference chemical geometry, not a deposited bound pose.\",\"identity_status\":\"complete_deposited_inchikey\",\"inchikey\":\"jqshbvhomnkwft-dtorhvgosa-n\",\"inventory_origin\":\"v1_ccd_inventory\",\"isomeric_smiles\":\"c1cnc2cc3c(cc2n1)[c@@h]4c[c@h]3cnc4\",\"primary_name\":\"varenicline\",\"retrieval_date\":\"2026-10-24\",\"smiles_stereo_by_ccd\":\"{\\\"qmr\\\": \\\"c1cnc2cc3c(cc2n1)[c@@h]4c[c@h]3cnc4\\\"}\",\"source_metadata_sha256\":\"{\\\"qmr\\\": \\\"0439a1f642c76ab4c22ef3c5263fd2b3dec2301d7a686de21385d3defd3e9814\\\"}\",\"source_urls\":[\"https://www.rcsb.org/ligand/qmr\"]} pmid:39031937 2024 https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.14981 pmid:39031937 2024 https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1873-3468.14981", "source_urls": [ "https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.14981", "https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1873-3468.14981", "https://www.rcsb.org/ligand/QMR" ], "verification_pending": false, "context_observations": [ { "DMSO_percent": null, "abstract_reported_endpoint": null, "abstract_reported_method": null, "abstract_reported_units": null, "abstract_reported_value": null, "assay_construct_end": 93, "assay_construct_start": 1, "assay_record_id": "PWWP:ASSAY:0010", "assay_type": "NMR chemical-shift perturbation Kd", "assay_value_transferred_to_modeled_stereoisomers": 0, "audit_decision": "retain_with_explicit_endpoint_and_identity", "baseline_assay_record": 1, "buffer": "HEPES-buffered saline; 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Construct is the source HDGFRP2 PWWP expression fragment (1–93) carrying the stated mutation. Replicate number and titration-specific temperature are not independently specified.", "replicates": null, "retrieval_date": "2026-10-26", "role": "experimentally_studied_ligand", "source_database": "Primary literature (Phase 5)", "source_id": "P5:S:WEI2024", "source_measurement_key": "ffcc722dc4af4f80ffe47c5d374303804d84ce0ece347772ae8ec971c8c8d9c4", "source_original": { "assay_construct_end": 93, "assay_construct_start": 1, "assay_context": "purified_mutant_domain", "assay_organism": "Homo sapiens", "assay_record_id": "PWWP5:ASSAY:0027", "assay_type": "NMR chemical-shift perturbation Kd", "assay_value_transferred_to_modeled_stereoisomers": false, "ccd_id": null, "chemical_id": "INCHIKEY:JQSHBVHOMNKWFT-DTORHVGOSA-N", "compound_name": "varenicline", "conditions": { "binding_model": "1:1 global fit of perturbed residues", "buffer": "HEPES-buffered saline; CSP subsection does not separately give HEPES/NaCl concentrations", "ligand_protein_molar_ratio_range": [ 0, 6 ], "pH": 7.4, "protein_concentration_mM": 0.1, "target_variant": "Y18S" }, "domain": "PWWP1", "domain_id": "UP:Q7Z4V5:PWWP1", "endpoint": "Kd", "evidence_class": "direct_binding_affinity", "evidence_location": "Results; Figure 2E", "evidence_url": "https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1873-3468.14981", "gene": "HDGFL2", "inclusion_rationale": "Primary source explicitly identifies this preparation, target context and observation.", "is_negative": false, "numeric_transcription_status": "source_preserved", "numeric_value_inferred_from_structure": false, "pH": 7.4, "pdb_id": null, "preparation_id": "PREP:VARENICLINE", "protein_id": "UP:Q7Z4V5", "publication_year": 2024, "reference_id": "PMID:39031937", "remaining_uncertainty": "Y18S mutant measurement; must not be pooled with wild-type affinity. Construct is the source HDGFRP2 PWWP expression fragment (1–93) carrying the stated mutation. Replicate number and titration-specific temperature are not independently specified.", "replicates": null, "retrieval_date": "2026-10-26", "role": "experimentally_studied_ligand", "source_id": "P5:S:WEI2024", "source_reported_uncertainty": "0.05", "source_reported_units": "mM", "source_reported_value": "0.78", "source_verification_scope": "Official publisher full HTML independently inspected: Methods, Results and Figures 1–4 captions; original Supplementary Figure S2 was not retrieved", "target_variant": "Y18S", "uncertainty": 0.05, "uncertainty_type": "fitting error", "uncertainty_uM": 50.0, "unit_conversion": "mM × 1000 = µM", "units": "mM", "value": 0.78, "value_operator": "=", "value_uM": 780.0, "verification_level": "primary_source_verified", "version": "phase5.chemical_curation.1.1.0" }, "source_reported_uncertainty": "0.05", "source_reported_units": "mM", "source_reported_value": "0.78", "source_verification_scope": "Official publisher full HTML independently inspected: Methods, Results and Figures 1–4 captions; original Supplementary Figure S2 was not retrieved", "target_scope": "domain_specific", "target_variant": "Y18S", "uncertainty": 0.05, "uncertainty_type": "fitting error", "uncertainty_uM": 50.0, "unit_conversion": "mM × 1000 = µM", "units": "mM", "value": 0.78, "value_operator": "=", "value_uM": 780.0, "verification_level": "primary_source_verified", "version": "phase5.chemical_curation.1.1.0" } ], "context_structures": [ { "Pfam_contacts_5A": "[{\"auth_asym_id\": \"B\", \"auth_seq_id\": \"15\", \"component\": \"MET\", \"entity_position\": 15, \"label_asym_id\": \"B\", \"minimum_distance_angstrom\": 3.579, \"uniprot_position\": 15}, {\"auth_asym_id\": \"B\", \"auth_seq_id\": \"18\", \"component\": \"TYR\", \"entity_position\": 18, \"label_asym_id\": \"B\", \"minimum_distance_angstrom\": 3.4485, \"uniprot_position\": 18}, {\"auth_asym_id\": \"B\", \"auth_seq_id\": \"21\", \"component\": \"TRP\", \"entity_position\": 21, \"label_asym_id\": \"B\", 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3.579, \"uniprot_position\": 15}, {\"auth_asym_id\": \"B\", \"auth_seq_id\": \"18\", \"component\": \"TYR\", \"entity_position\": 18, \"label_asym_id\": \"B\", \"minimum_distance_angstrom\": 3.4485, \"uniprot_position\": 18}, {\"auth_asym_id\": \"B\", \"auth_seq_id\": \"21\", \"component\": \"TRP\", \"entity_position\": 21, \"label_asym_id\": \"B\", \"minimum_distance_angstrom\": 3.6336, \"uniprot_position\": 21}, {\"auth_asym_id\": \"B\", \"auth_seq_id\": \"44\", \"component\": \"PHE\", \"entity_position\": 44, \"label_asym_id\": \"B\", \"minimum_distance_angstrom\": 3.5123, \"uniprot_position\": 44}, {\"auth_asym_id\": \"B\", \"auth_seq_id\": \"47\", \"component\": \"THR\", \"entity_position\": 47, \"label_asym_id\": \"B\", \"minimum_distance_angstrom\": 2.9898, \"uniprot_position\": 47}, {\"auth_asym_id\": \"B\", \"auth_seq_id\": \"49\", \"component\": \"GLU\", \"entity_position\": 49, \"label_asym_id\": \"B\", \"minimum_distance_angstrom\": 2.8063, \"uniprot_position\": 49}, 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\"label_asym_id\": \"B\", \"minimum_distance_angstrom\": 3.6336, \"uniprot_position\": null}, {\"auth_asym_id\": \"B\", \"auth_seq_id\": \"44\", \"component\": \"PHE\", \"entity_position\": 44, \"label_asym_id\": \"B\", \"minimum_distance_angstrom\": 3.5123, \"uniprot_position\": null}, {\"auth_asym_id\": \"B\", \"auth_seq_id\": \"47\", \"component\": \"THR\", \"entity_position\": 47, \"label_asym_id\": \"B\", \"minimum_distance_angstrom\": 2.9898, \"uniprot_position\": null}, {\"auth_asym_id\": \"B\", \"auth_seq_id\": \"49\", \"component\": \"GLU\", \"entity_position\": 49, \"label_asym_id\": \"B\", \"minimum_distance_angstrom\": 2.8063, \"uniprot_position\": null}, {\"auth_asym_id\": \"B\", \"auth_seq_id\": \"50\", \"component\": \"THR\", \"entity_position\": 50, \"label_asym_id\": \"B\", \"minimum_distance_angstrom\": 4.5483, \"uniprot_position\": null}, {\"auth_asym_id\": \"B\", \"auth_seq_id\": \"51\", \"component\": \"ALA\", \"entity_position\": 51, \"label_asym_id\": \"B\", \"minimum_distance_angstrom\": 3.8161, \"uniprot_position\": null}]", "pose_kind": "deposited_source_coordinates", "reference_model": "1", "source_coordinate_file": "Structures/HDGFL2__HUMAN__Q7Z4V5/Co-Crystals/8Z6O/original.cif", "source_coordinate_sha256": "80d1a2369d1ebdb0aa342c4273e6641a37cb6e245960b063aeeea5a83bd64ba9", "unique_heavy_atom_names": 16 }, "ligand_instance_id": "PDB:8Z6O:LIG:D:QMR:101:.", "ligand_label_asym_id": "D", "minimum_Pfam_distance_angstrom": 2.8063, "minimum_chain_distance_angstrom": 2.8063, "minimum_core_distance_angstrom": 2.8063, "multiple_contacting_mapped_chains": 0, "pdb_id": "8Z6O", "protein_id": "UP:Q7Z4V5", "protein_label_asym_id": "B", "rank_interpretation": "Distance rank among mapped chains only; crystal packing and biological site assignment require separate review.", "role": "experimentally studied ligand", "role_category": "functional", "site_id": "PDB:8Z6O:LIG:D:QMR:101:.:SITE:UP:Q7Z4V5:PWWP1:B", "source_coordinate_sha256": "80d1a2369d1ebdb0aa342c4273e6641a37cb6e245960b063aeeea5a83bd64ba9" } ], "context_assay_count": 2, "context_measured_count": 2, "context_bound_count": 1, "context_pdb_count": 1, "context_negative_count": 0, "context_is_probe": false, "context_bioactivity_only": false, "context_kind": "Measured + bound structure", "science": { "studied_compound": true, "measured_count": 2, "structural_research_ligand": true, "research_pdb_count": 1, "other_component": false, "component_site_count": 0, "verification_queue": false, "positive_direct_binder": true, "reported_probe": false, "reported_control": false, "cellular_activity": false, "protein_degradation": false, "bioactivity_only": false, "research_site_count": 1, "unknown_site_count": 0, "annotation_roles": [ "studied", "structural" ] }, "science_label": "Studied + deposited research ligand", "science_profile": { "annotation_roles": [ "studied", "structural" ], "cellular_activity": false, "chemical_id": "INCHIKEY:JQSHBVHOMNKWFT-DTORHVGOSA-N", "compound_id": "INCHIKEY:JQSHBVHOMNKWFT-DTORHVGOSA-N", "entity_kind": "chemical_identity", "identity_resolved": true, "measured_observation_count": 2, "name": "varenicline", "other_pdb_component": false, "other_site_count": 0, "positive_direct_binder": true, "primary_view": "studied", "protein_degradation": false, "reported_control": false, "reported_probe": false, "rule": "Independent source observations + per-site coordinate role, not universal pharmacology", "source_observation_ids": [ "PWWP:ASSAY:0010", "PWWP5:ASSAY:0027" ], "source_site_ids": [ "PDB:8Z6O:LIG:D:QMR:101:.:SITE:UP:Q7Z4V5:PWWP1:B" ], "structural_research_ligand": true, "structural_research_site_count": 1, "studied_compound": true, "total_observation_count": 2, "uncertain_site_count": 0, "uncertainty": "Classification is evidence- and experiment-scoped; missing assays do not prove nonbinding.", "verification_queue": false, "verification_status": "source_scoped_mixed" }, "science_site_roles": { "PDB:8Z6O:LIG:D:QMR:101:.:SITE:UP:Q7Z4V5:PWWP1:B": { "ccd_url": "https://www.rcsb.org/ligand/QMR", "chemical_id": "INCHIKEY:JQSHBVHOMNKWFT-DTORHVGOSA-N", "compound_id": "INCHIKEY:JQSHBVHOMNKWFT-DTORHVGOSA-N", "contact_class": "native_annotation_core_contact", "coordinate_sha256": "80d1a2369d1ebdb0aa342c4273e6641a37cb6e245960b063aeeea5a83bd64ba9", "domain_id": "UP:Q7Z4V5:PWWP1", "exact_pwwp_contact": true, "ligand_instance_id": "PDB:8Z6O:LIG:D:QMR:101:.", "observed_other_component": false, "pdb_id": "8Z6O", "protein_id": "UP:Q7Z4V5", "role_code": "reported_studied_structural_ligand", "role_group": "research_ligand", "rule": "Phase5 exact deposited site role, measured heavy-atom contacts and native-domain scope", "site_id": "PDB:8Z6O:LIG:D:QMR:101:.:SITE:UP:Q7Z4V5:PWWP1:B", "source_role": "experimentally studied ligand", "source_url": "https://www.rcsb.org/structure/8Z6O", "structural_research_ligand": true, "uncertainty": "Role is source-annotated; deposited proximity alone does not establish solution binding or biological activity.", "verification_status": "phase5_derived_deposited_geometry" } }, "science_assay_roles": { "PWWP:ASSAY:0010": { "chemical_id": "INCHIKEY:JQSHBVHOMNKWFT-DTORHVGOSA-N", "compound_id": "INCHIKEY:JQSHBVHOMNKWFT-DTORHVGOSA-N", "domain_id": "UP:Q7Z4V5:PWWP1", "endpoint": "Kd", "evidence_type": "direct_binding", "explicitly_negative": false, "measured": true, "method": "NMR chemical-shift perturbation", "molecular_entity_type": "small_molecule_preparation", "observation_id": "PWWP:ASSAY:0010", "operator": "=", "positive_direct_binder": true, "preparation_id": "PREP:VARENICLINE", "protein_id": "UP:Q7Z4V5", "remaining_uncertainty": "Full assay buffer, temperature and incubation metadata not transcribed; null means uncurated, not absent.", "reported_cellular": false, "reported_control": false, "reported_probe": false, "rule": "Phase5 source-curated evidence_class, material, target_scope, source role; no inferred affinities", "source_id": "S04", "source_location": "Results; Figure 1E", "source_role": "experimentally_studied_fragment_ligand", "source_url": "https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.14981", "source_verification_scope": "primary_publisher_selected_indexed_Results_and_Methods_passages; Figure S2 not independently retrieved", "studied_compound": true, "target_scope": "domain_specific", "target_variant": null, "units": "µM", "value": 250.0, "verification_status": "primary_full_text_sections_verified" }, "PWWP5:ASSAY:0027": { "chemical_id": "INCHIKEY:JQSHBVHOMNKWFT-DTORHVGOSA-N", "compound_id": "INCHIKEY:JQSHBVHOMNKWFT-DTORHVGOSA-N", "domain_id": "UP:Q7Z4V5:PWWP1", "endpoint": "Kd", "evidence_type": "direct_binding", "explicitly_negative": false, "measured": true, "method": "NMR chemical-shift perturbation", "molecular_entity_type": "small_molecule_preparation", "observation_id": "PWWP5:ASSAY:0027", "operator": "=", "positive_direct_binder": true, "preparation_id": "PREP:VARENICLINE", "protein_id": "UP:Q7Z4V5", "remaining_uncertainty": "Y18S mutant measurement; must not be pooled with wild-type affinity. Construct is the source HDGFRP2 PWWP expression fragment (1–93) carrying the stated mutation. Replicate number and titration-specific temperature are not independently specified.", "reported_cellular": false, "reported_control": false, "reported_probe": false, "rule": "Phase5 source-curated evidence_class, material, target_scope, source role; no inferred affinities", "source_id": "P5:S:WEI2024", "source_location": "Results; Figure 2E", "source_role": "experimentally_studied_ligand", "source_url": "https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1873-3468.14981", "source_verification_scope": "Official publisher full HTML independently inspected: Methods, Results and Figures 1–4 captions; original Supplementary Figure S2 was not retrieved", "studied_compound": true, "target_scope": "domain_specific", "target_variant": "Y18S", "units": "mM", "value": 0.78, "verification_status": "primary_source_verified" } }, "example": { "DMSO_percent": null, "abstract_reported_endpoint": null, "abstract_reported_method": null, "abstract_reported_units": null, "abstract_reported_value": null, "assay_construct_end": 93, "assay_construct_start": 1, "assay_record_id": "PWWP:ASSAY:0010", "assay_type": "NMR chemical-shift perturbation Kd", "assay_value_transferred_to_modeled_stereoisomers": 0, "audit_decision": "retain_with_explicit_endpoint_and_identity", "baseline_assay_record": 1, "buffer": "HEPES-buffered saline; exact buffer/salt concentrations not restated in CSP subsection", "ccd_id": "QMR", "ccd_mapping_source": "Provenance/Literature/ligand_ccd_associations.json", "chemical_id": "INCHIKEY:JQSHBVHOMNKWFT-DTORHVGOSA-N", "chemical_identity_status": "exact_single_CCD_identity", "component_context": null, "compound_id": "INCHIKEY:JQSHBVHOMNKWFT-DTORHVGOSA-N", "compound_name": "varenicline", "conditions": "{\"fit_model\": \"1:1 binding; global fit with shared Kd\", \"ligand_to_protein_molar_ratio_range\": [0, 6], \"protein_concentration_uM\": 100, \"protein_construct\": \"HDGFL2 1–93\"}", "crystallographic_component_ids": null, "curation_version": "frozen-v1.2", "domain": "PWWP", "domain_id": "UP:Q7Z4V5:PWWP1", "endpoint": "Kd", "endpoint_label_status": null, "evidence_class": "direct_binding_affinity", "evidence_location": "Results; Figure 1E", "evidence_url": "https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.14981", "gene": "HDGFL2", "interpretation": "Converted from 0.25 ± 0.04 mM. Receptor pharmacology in other systems is not evidence of PWWP potency.", "is_measured": true, "is_negative": false, "method": "NMR chemical-shift perturbation", "molecular_entity_type": "small_molecule_preparation", "normalized_exact_uM": 250.0, "numeric_transcription_status": "matches_primary_report", "numeric_value_inferred_from_structure": 0, "organism": "Homo sapiens", "pH": 7.4, "pdb_id": "8Z6O", "preparation_id": "PREP:VARENICLINE", "protein_id": "UP:Q7Z4V5", "publication_year": 2024, "qualitative_result": null, "reference_id": "PMID:39031937", "remaining_uncertainty": "Full assay buffer, temperature and incubation metadata not transcribed; null means uncurated, not absent.", "replicates": null, "role": "experimentally_studied_fragment_ligand", "source_component_url": null, "source_database": "Primary literature (frozen Atlas)", "source_id": "S04", "source_measurement_key": "2b9c01d4150ca3f35a87bce9ed5d4dde79bfafc9ecb109e3891ecdca18c484f1", "source_original": { "DMSO_percent": null, "abstract_reported_endpoint": null, "abstract_reported_method": null, "abstract_reported_units": null, "abstract_reported_value": null, "assay_construct_end": 93, "assay_construct_start": 1, "assay_record_id": "PWWP:ASSAY:0010", "assay_type": "NMR chemical-shift perturbation Kd", "assay_value_transferred_to_modeled_stereoisomers": 0, "audit_decision": "retain_with_explicit_endpoint_and_identity", "baseline_assay_record": 1, "buffer": "HEPES-buffered saline; exact buffer/salt concentrations not restated in CSP subsection", "ccd_id": "QMR", "ccd_mapping_source": "Provenance/Literature/ligand_ccd_associations.json", "chemical_id": "INCHIKEY:JQSHBVHOMNKWFT-DTORHVGOSA-N", "chemical_identity_status": "exact_single_CCD_identity", "component_context": null, "compound_name": "varenicline", "conditions": "{\"fit_model\": \"1:1 binding; global fit with shared Kd\", \"ligand_to_protein_molar_ratio_range\": [0, 6], \"protein_concentration_uM\": 100, \"protein_construct\": \"HDGFL2 1–93\"}", "crystallographic_component_ids": null, "domain": "PWWP", "domain_id": "UP:Q7Z4V5:PWWP1", "endpoint_label_status": null, "evidence_class": "direct_binding_affinity", "evidence_location": "Results; Figure 1E", "evidence_url": "https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.14981", "gene": "HDGFL2", "interpretation": "Converted from 0.25 ± 0.04 mM. Receptor pharmacology in other systems is not evidence of PWWP potency.", "molecular_entity_type": "small_molecule_preparation", "numeric_transcription_status": "matches_primary_report", "numeric_value_inferred_from_structure": 0, "pH": 7.4, "pdb_id": "8Z6O", "preparation_id": "PREP:VARENICLINE", "protein_id": "UP:Q7Z4V5", "qualitative_result": null, "reference_id": "PMID:39031937", "remaining_uncertainty": "Full assay buffer, temperature and incubation metadata not transcribed; null means uncurated, not absent.", "replicates": null, "role": "experimentally_studied_fragment_ligand", "source_component_url": null, "source_id": "S04", "source_reported_uncertainty": "0.04", "source_reported_units": "mM", "source_reported_value": "0.25", "source_verification_scope": "primary_publisher_selected_indexed_Results_and_Methods_passages; Figure S2 not independently retrieved", "temperature_C": null, "uncertainty": 40.0, "uncertainty_type": "fitting_error", "uncertainty_uM": 40.0, "unit_conversion": "0.25 mM × 1000 = 250 µM; 0.04 mM × 1000 = 40 µM", "units": "µM", "value": 250.0, "value_operator": "=", "value_uM": 250.0, "verification_level": "primary_full_text_sections_verified" }, "source_reported_uncertainty": "0.04", "source_reported_units": "mM", "source_reported_value": "0.25", "source_verification_scope": "primary_publisher_selected_indexed_Results_and_Methods_passages; Figure S2 not independently retrieved", "target_scope": "domain_specific", "temperature_C": null, "uncertainty": 40.0, "uncertainty_type": "fitting_error", "uncertainty_uM": 40.0, "unit_conversion": "0.25 mM × 1000 = 250 µM; 0.04 mM × 1000 = 40 µM", "units": "µM", "value": 250.0, "value_operator": "=", "value_uM": 250.0, "verification_level": "primary_full_text_sections_verified" }, "matched_observations": [ { "DMSO_percent": null, "abstract_reported_endpoint": null, "abstract_reported_method": null, "abstract_reported_units": null, "abstract_reported_value": null, "assay_construct_end": 93, "assay_construct_start": 1, "assay_record_id": "PWWP:ASSAY:0010", "assay_type": "NMR chemical-shift perturbation Kd", "assay_value_transferred_to_modeled_stereoisomers": 0, "audit_decision": "retain_with_explicit_endpoint_and_identity", "baseline_assay_record": 1, "buffer": "HEPES-buffered saline; exact buffer/salt concentrations not restated in CSP subsection", "ccd_id": "QMR", "ccd_mapping_source": "Provenance/Literature/ligand_ccd_associations.json", "chemical_id": "INCHIKEY:JQSHBVHOMNKWFT-DTORHVGOSA-N", "chemical_identity_status": "exact_single_CCD_identity", "component_context": null, "compound_id": "INCHIKEY:JQSHBVHOMNKWFT-DTORHVGOSA-N", "compound_name": "varenicline", "conditions": "{\"fit_model\": \"1:1 binding; global fit with shared Kd\", \"ligand_to_protein_molar_ratio_range\": [0, 6], \"protein_concentration_uM\": 100, \"protein_construct\": \"HDGFL2 1–93\"}", "crystallographic_component_ids": null, "curation_version": "frozen-v1.2", "domain": "PWWP", "domain_id": "UP:Q7Z4V5:PWWP1", "endpoint": "Kd", "endpoint_label_status": null, "evidence_class": "direct_binding_affinity", "evidence_location": "Results; Figure 1E", "evidence_url": "https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.14981", "gene": "HDGFL2", "interpretation": "Converted from 0.25 ± 0.04 mM. Receptor pharmacology in other systems is not evidence of PWWP potency.", "is_measured": true, "is_negative": false, "method": "NMR chemical-shift perturbation", "molecular_entity_type": "small_molecule_preparation", "normalized_exact_uM": 250.0, "numeric_transcription_status": "matches_primary_report", "numeric_value_inferred_from_structure": 0, "organism": "Homo sapiens", "pH": 7.4, "pdb_id": "8Z6O", "preparation_id": "PREP:VARENICLINE", "protein_id": "UP:Q7Z4V5", "publication_year": 2024, "qualitative_result": null, "reference_id": "PMID:39031937", "remaining_uncertainty": "Full assay buffer, temperature and incubation metadata not transcribed; null means uncurated, not absent.", "replicates": null, "role": "experimentally_studied_fragment_ligand", "source_component_url": null, "source_database": "Primary literature (frozen Atlas)", "source_id": "S04", "source_measurement_key": "2b9c01d4150ca3f35a87bce9ed5d4dde79bfafc9ecb109e3891ecdca18c484f1", "source_original": { "DMSO_percent": null, "abstract_reported_endpoint": null, "abstract_reported_method": null, "abstract_reported_units": null, "abstract_reported_value": null, "assay_construct_end": 93, "assay_construct_start": 1, "assay_record_id": "PWWP:ASSAY:0010", "assay_type": "NMR chemical-shift perturbation Kd", "assay_value_transferred_to_modeled_stereoisomers": 0, "audit_decision": "retain_with_explicit_endpoint_and_identity", "baseline_assay_record": 1, "buffer": "HEPES-buffered saline; exact buffer/salt concentrations not restated in CSP subsection", "ccd_id": "QMR", "ccd_mapping_source": "Provenance/Literature/ligand_ccd_associations.json", "chemical_id": "INCHIKEY:JQSHBVHOMNKWFT-DTORHVGOSA-N", "chemical_identity_status": "exact_single_CCD_identity", "component_context": null, "compound_name": "varenicline", "conditions": "{\"fit_model\": \"1:1 binding; global fit with shared Kd\", \"ligand_to_protein_molar_ratio_range\": [0, 6], \"protein_concentration_uM\": 100, \"protein_construct\": \"HDGFL2 1–93\"}", "crystallographic_component_ids": null, "domain": "PWWP", "domain_id": "UP:Q7Z4V5:PWWP1", "endpoint_label_status": null, "evidence_class": "direct_binding_affinity", "evidence_location": "Results; Figure 1E", "evidence_url": "https://febs.onlinelibrary.wiley.com/doi/10.1002/1873-3468.14981", "gene": "HDGFL2", "interpretation": "Converted from 0.25 ± 0.04 mM. Receptor pharmacology in other systems is not evidence of PWWP potency.", "molecular_entity_type": "small_molecule_preparation", "numeric_transcription_status": "matches_primary_report", "numeric_value_inferred_from_structure": 0, "pH": 7.4, "pdb_id": "8Z6O", "preparation_id": "PREP:VARENICLINE", "protein_id": "UP:Q7Z4V5", "qualitative_result": null, "reference_id": "PMID:39031937", "remaining_uncertainty": "Full assay buffer, temperature and incubation metadata not transcribed; null means uncurated, not absent.", "replicates": null, "role": "experimentally_studied_fragment_ligand", "source_component_url": null, "source_id": "S04", "source_reported_uncertainty": "0.04", "source_reported_units": "mM", "source_reported_value": "0.25", "source_verification_scope": "primary_publisher_selected_indexed_Results_and_Methods_passages; Figure S2 not independently retrieved", "temperature_C": null, "uncertainty": 40.0, "uncertainty_type": "fitting_error", "uncertainty_uM": 40.0, "unit_conversion": "0.25 mM × 1000 = 250 µM; 0.04 mM × 1000 = 40 µM", "units": "µM", "value": 250.0, "value_operator": "=", "value_uM": 250.0, "verification_level": "primary_full_text_sections_verified" }, "source_reported_uncertainty": "0.04", "source_reported_units": "mM", "source_reported_value": "0.25", "source_verification_scope": "primary_publisher_selected_indexed_Results_and_Methods_passages; Figure S2 not independently retrieved", "target_scope": "domain_specific", "temperature_C": null, "uncertainty": 40.0, "uncertainty_type": "fitting_error", "uncertainty_uM": 40.0, "unit_conversion": "0.25 mM × 1000 = 250 µM; 0.04 mM × 1000 = 40 µM", "units": "µM", "value": 250.0, "value_operator": "=", "value_uM": 250.0, "verification_level": "primary_full_text_sections_verified" }, { "assay_construct_end": 93, "assay_construct_start": 1, "assay_context": "purified_mutant_domain", "assay_organism": "Homo sapiens", "assay_record_id": "PWWP5:ASSAY:0027", "assay_type": "NMR chemical-shift perturbation Kd", "assay_value_transferred_to_modeled_stereoisomers": false, "ccd_id": null, "chemical_id": "INCHIKEY:JQSHBVHOMNKWFT-DTORHVGOSA-N", "compound_id": "INCHIKEY:JQSHBVHOMNKWFT-DTORHVGOSA-N", "compound_name": "varenicline", "conditions": { "binding_model": "1:1 global fit of perturbed residues", "buffer": "HEPES-buffered saline; CSP subsection does not separately give HEPES/NaCl concentrations", "ligand_protein_molar_ratio_range": [ 0, 6 ], "pH": 7.4, "protein_concentration_mM": 0.1, "target_variant": "Y18S" }, "curation_version": "phase5-1.0.0", "domain": "PWWP1", "domain_id": "UP:Q7Z4V5:PWWP1", "endpoint": "Kd", "evidence_class": "direct_binding_affinity", "evidence_location": "Results; Figure 2E", "evidence_url": "https://febs.onlinelibrary.wiley.com/doi/full/10.1002/1873-3468.14981", "gene": "HDGFL2", "inclusion_rationale": "Primary source explicitly identifies this preparation, target context and observation.", "is_measured": true, "is_negative": false, "method": "NMR chemical-shift perturbation", "normalized_exact_uM": 780.0, "numeric_transcription_status": "source_preserved", "numeric_value_inferred_from_structure": false, "organism": "Homo sapiens", "pH": 7.4, "pdb_id": null, "preparation_id": "PREP:VARENICLINE", "protein_id": "UP:Q7Z4V5", "publication_year": 2024, "reference_id": "PMID:39031937", "remaining_uncertainty": "Y18S mutant measurement; must not be pooled with wild-type affinity. Construct is the source HDGFRP2 PWWP expression fragment (1–93) carrying the stated mutation. 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Construct is the source HDGFRP2 PWWP expression fragment (1–93) carrying the stated mutation. 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