PCSK9 inhibitor chemical & modality series

PCSK9 / LDL-CRefresh recommended

Oral macrocyclic peptide PCSK9i (enlicitide / Lipfendra) mapped with injectable mAb (evolocumab, alirocumab) and siRNA (inclisiran) class peers for LDL-C lowering.

Mechanism · PCSK9 / LDL-C BioMoa · PCSK9 / LDL-C BioMoa bridge · shared ID

Last analysis: 7/20/2026, 2:09:52 AM · 2 weeks cadence · refresh on /analyze · refresh recommended

Data sources: Catalog seed · ChEMBL · PubChem · ClinicalTrials.gov · FDA/EMA · Investigational
Last updated: 7/20/2026, 2:09:52 AM
Similarity method: Morgan fingerprint, radius 2, 2048 bits, Tanimoto
Verified / known compounds: 5
Exploratory nodes: 3
Abstract scaffolds: 1
Relationship types: Derived (curated) · Fingerprint similarity · Drug-class link

StructureMoa is a chemical-structure exploration tool. Structural similarity, clustering, and SAR relationships are intended for research exploration and do not establish shared potency, selectivity, safety, efficacy, or clinical performance.

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Name, 2D structure, SMILES, role, parent, core similarity, and traits. Click a row for details.

Compound	Role	SMILES	Parent	Core sim.	Traits
PCSK9-binding macrocyclic peptide pharmacophoreAbstract pharmacophorepcsk9-macrocycle-corePage	Scaffold	`CC(C)C[C@H]1NC(=O)[C@H](Cc2ccccc2)NC(=O)[C…`	—	—	PCSK9 · macrocycle · core · LDL-C · Shared pharmacophore / core scaffold. Anchor for the PCSK9 inhibitor chemical & modality s…
Alirocumab (Praluent)Verified drugalirocumabPage	Drug	`CC(C)C[C@H](NC(=O)[C@H](Cc1ccc(O)cc1)N)C(=…`	PCSK9-binding macrocyclic peptide pharmacophore	17%i	approved · PCSK9 · mAb · injectable · Approved therapeutic. Alirocumab (Praluent) in this family map. · CHEMBL1743034
Enlicitide (Lipfendra)Verified drugenlicitidePage	Drug	`CC(C)C[C@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O…`	PCSK9-binding macrocyclic peptide pharmacophore	66%i	approved · PCSK9 · oral · Lipfendra · MK-0616 · First FDA-approved once-daily oral PCSK9 inhibitor (macrocyclic peptide); adjunct to diet/…
Evolocumab (Repatha)Verified drugevolocumabPage	Drug	`CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)N)C(=O)N…`	PCSK9-binding macrocyclic peptide pharmacophore	22%i	approved · PCSK9 · mAb · injectable · Anti-PCSK9 monoclonal antibody — Q2W/QM SC injection class peer to oral enlicitide. · CHEMBL2107838
Inclisiran (Leqvio)Verified druginclisiranPage	Drug	`Nc1nc2c(ncn2[C@@H]2O[C@H](COP(=O)(O)O)[C@@…`	PCSK9-binding macrocyclic peptide pharmacophore	9%i	approved · PCSK9 · siRNA · injectable · PCSK9-targeting siRNA — twice-yearly dosing after loading; modality contrast to oral pepti… · CID 133086079
Lerodalcibep (LIB003)Known compoundlerodalcibepPage	Drug	`CC(C)C[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](C…`	PCSK9-binding macrocyclic peptide pharmacophore	25%i	clinical · PCSK9 · adnectin · Clinical-stage candidate. Lerodalcibep (LIB003) in this family map.
MK-0616 (enlicitide development code)Exploratory analogmk-0616Page	Derivative	`CC(C)C[C@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O…`	Enlicitide (Lipfendra)	66%i	clinical · PCSK9 · oral · Clinical-stage candidate. Derived analog of parent node in PCSK9 inhibitor chemical & moda…
Oral PCSK9i amide SAR analogExploratory analog (rule-generated)pcsk9-oral-sar-amidePage	Derivative	`CC(C)C[C@H]1NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O…`	Enlicitide (Lipfendra)	65%i	SAR · oral · PCSK9 · SAR exploration node. Derived analog of parent node in PCSK9 inhibitor chemical & modality…
Oral PCSK9i fluoro-macrocycle analogExploratory analog (rule-generated)pcsk9-oral-sar-fluoroPage	Derivative	`CC(C)C[C@H]1NC(=O)[C@H](Cc2ccc(F)cc2)NC(=O…`	Oral PCSK9i amide SAR analog	65%i	SAR · F-scan · PCSK9 · SAR exploration node. Derived analog of parent node in PCSK9 inhibitor chemical & modality…

Name	Role	Derived from	Sim. to core	Relations	Tags
Alirocumab (Praluent)Verified drug	Drug	PCSK9-binding macrocyclic peptide pharmacophore	17%i	derived_from: PCSK9-binding macrocyclic peptide pharmacophore · similar_to: Evolocumab (Repatha) · related_drug: Evolocumab (Repatha) · similar_to: PCSK9-binding macrocyclic peptide pharmacophore	approved, PCSK9, mAb, injectable
Enlicitide (Lipfendra)Verified drug	Drug	PCSK9-binding macrocyclic peptide pharmacophore	66%i	derived_from: PCSK9-binding macrocyclic peptide pharmacophore · derived_from: MK-0616 (enlicitide development code) · derived_from: Oral PCSK9i amide SAR analog · similar_to: Evolocumab (Repatha) · related_drug: Lerodalcibep (LIB003) · related_drug: Evolocumab (Repatha) · related_drug: Inclisiran (Leqvio) · similar_to: Oral PCSK9i fluoro-macrocycle analog · similar_to: Oral PCSK9i amide SAR analog · similar_to: PCSK9-binding macrocyclic peptide pharmacophore · similar_to: MK-0616 (enlicitide development code)	approved, PCSK9, oral, Lipfendra, MK-0616
Evolocumab (Repatha)Verified drug	Drug	PCSK9-binding macrocyclic peptide pharmacophore	22%i	derived_from: PCSK9-binding macrocyclic peptide pharmacophore · similar_to: Enlicitide (Lipfendra) · similar_to: Alirocumab (Praluent) · related_drug: Enlicitide (Lipfendra) · related_drug: Alirocumab (Praluent) · similar_to: PCSK9-binding macrocyclic peptide pharmacophore	approved, PCSK9, mAb, injectable
Inclisiran (Leqvio)Verified drug	Drug	PCSK9-binding macrocyclic peptide pharmacophore	9%i	derived_from: PCSK9-binding macrocyclic peptide pharmacophore · related_drug: Enlicitide (Lipfendra) · similar_to: PCSK9-binding macrocyclic peptide pharmacophore	approved, PCSK9, siRNA, injectable
Lerodalcibep (LIB003)Known compound	Drug	PCSK9-binding macrocyclic peptide pharmacophore	25%i	derived_from: PCSK9-binding macrocyclic peptide pharmacophore · related_drug: Enlicitide (Lipfendra) · similar_to: PCSK9-binding macrocyclic peptide pharmacophore	clinical, PCSK9, adnectin
MK-0616 (enlicitide development code)Exploratory analog	Derivative	Enlicitide (Lipfendra)	66%i	derived_from: Enlicitide (Lipfendra) · similar_to: Oral PCSK9i amide SAR analog · similar_to: Oral PCSK9i fluoro-macrocycle analog · similar_to: PCSK9-binding macrocyclic peptide pharmacophore · similar_to: Enlicitide (Lipfendra)	clinical, PCSK9, oral
Oral PCSK9i amide SAR analogExploratory analog (rule-generated)	Derivative	Enlicitide (Lipfendra)	65%i	derived_from: Oral PCSK9i fluoro-macrocycle analog · derived_from: Enlicitide (Lipfendra) · similar_to: MK-0616 (enlicitide development code) · similar_to: Enlicitide (Lipfendra) · similar_to: Oral PCSK9i fluoro-macrocycle analog · similar_to: PCSK9-binding macrocyclic peptide pharmacophore	SAR, oral, PCSK9
Oral PCSK9i fluoro-macrocycle analogExploratory analog (rule-generated)	Derivative	Oral PCSK9i amide SAR analog	65%i	derived_from: Oral PCSK9i amide SAR analog · similar_to: Enlicitide (Lipfendra) · similar_to: Oral PCSK9i amide SAR analog · similar_to: PCSK9-binding macrocyclic peptide pharmacophore · similar_to: MK-0616 (enlicitide development code)	SAR, F-scan, PCSK9
PCSK9-binding macrocyclic peptide pharmacophoreAbstract pharmacophore	Scaffold	—	—	derived_from: Enlicitide (Lipfendra) · derived_from: Alirocumab (Praluent) · derived_from: Evolocumab (Repatha) · derived_from: Inclisiran (Leqvio) · derived_from: Lerodalcibep (LIB003) · similar_to: Evolocumab (Repatha) · similar_to: Alirocumab (Praluent) · similar_to: Inclisiran (Leqvio) · similar_to: Lerodalcibep (LIB003) · similar_to: Oral PCSK9i amide SAR analog · similar_to: Oral PCSK9i fluoro-macrocycle analog · similar_to: Enlicitide (Lipfendra) · similar_to: MK-0616 (enlicitide development code)	PCSK9, macrocycle, core, LDL-C

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Clinical · regulatory context

PCSK9 — 주사 + 경구 매크로사이클

mAb/siRNA 승인과 경구 peptide(enlicitide) 임상 축이 공존합니다.

Approved/clinical labels here come from the catalog clinical overlay. Agency names are shown when curated; live FDA/EMA APIs are not called.

EvolocumabApprovedFDA/EMA
Hypercholesterolemia / ASCVD
ClinicalTrials.gov
Enlicitide (Lipfendra)P3Investigational
Oral macrocyclic PCSK9i
ClinicalTrials.gov

Program and pipeline notes live on BioMoa · pcsk9 · StructureMoa ↔ BioMoa bridge