Resolved chemical identity

varenicline

Studied + deposited research ligand

Complete deposited identity retained; no connectivity-only or name-only merge.

2 assay / association records1 preparations1 research-ligand PDB entries

Clinical / development status: Not independently curated. A chemical probe classification does not imply medicinal approval.

Identity is separate from preparation

Chemical identity

Stable identity: INCHIKEY:JQSHBVHOMNKWFT-DTORHVGOSA-N
Full InChIKey: JQSHBVHOMNKWFT-DTORHVGOSA-N
Source identity status: complete deposited InChIKey
Deposited CCD identifiers: QMR
External identifiers: See deposited identity and source links

Reference formula: C13H13N3
Calculated molecular weight: 211.268
Calculated descriptors: cLogP 1.8039 · TPSA 37.81 Å² · HBD 1 · HBA 3RDKit 2025.09.3; calculations for this source identity, not experimental measurements.
Depiction validation: verified smiles full inchikey match

SMILES, InChI & complete identity record

Isomeric SMILES: c1cnc2cc3c(cc2n1)[C@@H]4C[C@H]3CNC4
InChI: Not curated

{
  "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"
  ]
}

Source aliases (2)

VARENICLINE
varenicline

Measured target and original context

Bioactivity & experimental observations

Download assay CSV

Each row is one source-specific observation. Repeated measurements of this compound are not independent compounds. Direct binding, functional displacement and cellular outcomes retain their distinct endpoints.

Preparation	Tested target & construct	Method / endpoint	Original observation	Conditions & uncertainty	Source & verification
vareniclinePREP:VARENICLINE	HDGFL2 PWWP 1–93Homo sapiens	KdNMR chemical-shift perturbation Kddirect binding affinity	= 250 ± 40 µM250 µM · exact unit conversion	Experimental context Replicates Not curated Uncertainty definition fitting_error Temperature — Buffer HEPES-buffered saline; exact buffer/salt concentrations not restated in CSP subsection 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"} Qualification Full assay buffer, temperature and incubation metadata not transcribed; null means uncurated, not absent.	PMID:39031937 · 2024primary_publisher_selected_indexed_Results_and_Methods_passages; Figure S2 not independently retrieved Original observation record { "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, "baseline_original": "{\"assay_record_id\": \"PWWP:ASSAY:0010\", \"assay_type\": \"NMR chemical-shift perturbation Kd\", \"ccd_id\": \"QMR\", \"ccd_mapping_source\": \"Provenance/Literature/ligand_ccd_associations.json\", \"compound_name\": \"varenicline\", \"conditions\": {}, \"domain\": \"PWWP\", \"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 \u00b1 0.04 mM. Receptor pharmacology in other systems is not evidence of PWWP potency.\", \"numeric_value_inferred_from_structure\": false, \"pdb_id\": \"8Z6O\", \"reference_id\": \"PMID:39031937\", \"role\": \"experimentally_studied_fragment_ligand\", \"uncertainty\": 40, \"units\": \"\u00b5M\", \"value\": 250, \"value_operator\": \"=\", \"verification_level\": \"primary_full_text_sections_verified\"}", "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\u201393\"}", "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 \u00b1 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 \u00d7 1000 = 250 \u00b5M; 0.04 mM \u00d7 1000 = 40 \u00b5M", "units": "\u00b5M", "value": 250.0, "value_operator": "=", "value_uM": 250.0, "verification_level": "primary_full_text_sections_verified" }
vareniclinePREP:VARENICLINE	HDGFL2 PWWP1 1–93Variant: Y18SHomo sapiens	KdNMR chemical-shift perturbation Kddirect binding affinity	= 0.78 ± 0.05 mM780 µM · exact unit conversion	Experimental context Replicates Not curated Uncertainty definition fitting error Temperature °C Buffer Not curated 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'} Qualification 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.	PMID:39031937 · 2024Official publisher full HTML independently inspected: Methods, Results and Figures 1–4 captions; original Supplementary Figure S2 was not retrieved Original observation record { "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\u201393) 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\u20134 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 \u00d7 1000 = \u00b5M", "units": "mM", "value": 0.78, "value_operator": "=", "value_uM": 780.0, "verification_level": "primary_source_verified", "version": "phase5.chemical_curation.1.1.0" }

Preparation

Tested target & construct

Method / endpoint

Original observation

Conditions & uncertainty

Source & verification

vareniclinePREP:VARENICLINE

HDGFL2 PWWP
1–93Homo sapiens

KdNMR chemical-shift perturbation Kddirect binding affinity

= 250 ± 40 µM250 µM · exact unit conversion

Experimental context

Replicates: Not curated
Uncertainty definition: fitting_error
Temperature: —
Buffer: HEPES-buffered saline; exact buffer/salt concentrations not restated in CSP subsection
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"}
Qualification: Full assay buffer, temperature and incubation metadata not transcribed; null means uncurated, not absent.

PMID:39031937 · 2024primary_publisher_selected_indexed_Results_and_Methods_passages; Figure S2 not independently retrieved

Original observation record

{
  "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,
  "baseline_original": "{\"assay_record_id\": \"PWWP:ASSAY:0010\", \"assay_type\": \"NMR chemical-shift perturbation Kd\", \"ccd_id\": \"QMR\", \"ccd_mapping_source\": \"Provenance/Literature/ligand_ccd_associations.json\", \"compound_name\": \"varenicline\", \"conditions\": {}, \"domain\": \"PWWP\", \"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 \u00b1 0.04 mM. Receptor pharmacology in other systems is not evidence of PWWP potency.\", \"numeric_value_inferred_from_structure\": false, \"pdb_id\": \"8Z6O\", \"reference_id\": \"PMID:39031937\", \"role\": \"experimentally_studied_fragment_ligand\", \"uncertainty\": 40, \"units\": \"\u00b5M\", \"value\": 250, \"value_operator\": \"=\", \"verification_level\": \"primary_full_text_sections_verified\"}",
  "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\u201393\"}",
  "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 \u00b1 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 \u00d7 1000 = 250 \u00b5M; 0.04 mM \u00d7 1000 = 40 \u00b5M",
  "units": "\u00b5M",
  "value": 250.0,
  "value_operator": "=",
  "value_uM": 250.0,
  "verification_level": "primary_full_text_sections_verified"
}

vareniclinePREP:VARENICLINE

HDGFL2 PWWP1
1–93Variant: Y18SHomo sapiens

KdNMR chemical-shift perturbation Kddirect binding affinity

= 0.78 ± 0.05 mM780 µM · exact unit conversion

Experimental context

Replicates: Not curated
Uncertainty definition: fitting error
Temperature: °C
Buffer: Not curated
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'}
Qualification: 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.

PMID:39031937 · 2024Official publisher full HTML independently inspected: Methods, Results and Figures 1–4 captions; original Supplementary Figure S2 was not retrieved

Original observation record

{
  "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\u201393) 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\u20134 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 \u00d7 1000 = \u00b5M",
  "units": "mM",
  "value": 0.78,
  "value_operator": "=",
  "value_uM": 780.0,
  "verification_level": "primary_source_verified",
  "version": "phase5.chemical_curation.1.1.0"
}

Exact deposited instances

Experimental structures

Native-core and broader Pfam proximity are distinguished from contacts elsewhere in a protein. Each action opens the actual deposited ligand instance. Geometric proximity does not supply a measured binding affinity.

Entry / ligand	Native domain & protein chain	Geometric evidence	Minimum distance	Inspect
8Z6O · QMRPDB:8Z6O:LIG:D:QMR:101:.	HDGFL2 PWWP1Protein label chain B · ligand label chain D	native annotation core contactexperimentally studied ligandreported studied structural ligand · research ligand. Deposited geometry is not solution affinity.	Core: 2.8063 Å Pfam: 2.8063 Å	View deposited instance

Preparations, identities and controls remain separate

Experimental context

varenicline

PREP:VARENICLINE

Complete deposited identity retained; no connectivity-only or name-only merge.

assay preparation

Complete preparation record

{
  "chemical_id": "INCHIKEY:JQSHBVHOMNKWFT-DTORHVGOSA-N",
  "entity_type": "small_molecule_preparation",
  "exact_ccd_id": "QMR",
  "identity_note": "Complete deposited identity retained; no connectivity-only or name-only merge.",
  "identity_status": "exact_single_CCD_identity",
  "modeled_candidate_ccd_ids": "[]",
  "modeled_candidate_chemical_ids": "[]",
  "name": "varenicline",
  "preparation_id": "PREP:VARENICLINE",
  "role": "assay_preparation",
  "sequence_if_defined": null
}

Provenance and reproducibility

Sources & downloads

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

Download complete evidence JSON Curation methods & source receipts

Snapshot 2026-10-26 · phase5-1.0.0 · original measurements, operators, constructs and uncertainty are retained in the exports.