FAP

Summary

FAP (fibroblast activation protein alpha, HGNC:3590) is a protein-coding gene on chromosome 2q24.2, encoding Prolyl endopeptidase FAP (Q12884). Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammation and tumor growth.

The protein encoded by this gene is a homodimeric integral membrane gelatinase belonging to the serine protease family. It is selectively expressed in reactive stromal fibroblasts of epithelial cancers, granulation tissue of healing wounds, and malignant cells of bone and soft tissue sarcomas. This protein is thought to be involved in the control of fibroblast growth or epithelial-mesenchymal interactions during development, tissue repair, and epithelial carcinogenesis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2191 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 126 total
• Druggable target: yes — 14 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004460

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3590
Approved symbol	FAP
Name	fibroblast activation protein alpha
Location	2q24.2
Locus type	gene with protein product
Status	Approved
Aliases	DPPIV
Ensembl gene	ENSG00000078098
Ensembl biotype	protein_coding
OMIM	600403
Entrez	2191

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 8 protein_coding, 6 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000188790, ENST00000422436, ENST00000443424, ENST00000447386, ENST00000450031, ENST00000461506, ENST00000462608, ENST00000465088, ENST00000465424, ENST00000480044, ENST00000480838, ENST00000493182, ENST00000497414, ENST00000856821, ENST00000856822, ENST00000856823, ENST00000963584, ENST00000963585

RefSeq mRNA: 2 — MANE Select: NM_004460 NM_001291807, NM_004460

CCDS: CCDS33311, CCDS77480

Canonical transcript exons

ENST00000188790 — 26 exons

Exon	Start	End
ENSE00000779544	162209952	162209996
ENSE00000779554	162226523	162226621
ENSE00001378583	162243322	162243445
ENSE00003299338	162198757	162198881
ENSE00003476170	162202872	162202942
ENSE00003476607	162173723	162173787
ENSE00003496869	162183414	162183468
ENSE00003508374	162200566	162200619
ENSE00003512558	162189656	162189754
ENSE00003519336	162173149	162173221
ENSE00003551517	162203041	162203145
ENSE00003552733	162188169	162188363
ENSE00003554519	162189103	162189172
ENSE00003564006	162174867	162174966
ENSE00003565447	162242908	162242992
ENSE00003570908	162219853	162219925
ENSE00003578117	162225483	162225577
ENSE00003595174	162213938	162214073
ENSE00003608429	162219063	162219183
ENSE00003646420	162172811	162172884
ENSE00003656394	162224466	162224540
ENSE00003666340	162194701	162194748
ENSE00003668648	162223608	162223660
ENSE00003687258	162217986	162218140
ENSE00003692825	162215898	162216001
ENSE00003843462	162170684	162171080

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 98.70.

FANTOM5 (CAGE): breadth broad, TPM avg 26.7184 / max 814.3201, expressed in 876 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
31541	24.2599	812
31543	1.1392	371
31542	0.9483	399
31540	0.3587	165
31544	0.0122	3

Top tissues by expression

286 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	98.70	gold quality
islet of Langerhans	UBERON:0000006	94.17	gold quality
body of uterus	UBERON:0009853	94.09	gold quality
smooth muscle tissue	UBERON:0001135	94.08	gold quality
cartilage tissue	UBERON:0002418	92.79	gold quality
gall bladder	UBERON:0002110	92.33	gold quality
decidua	UBERON:0002450	92.23	gold quality
descending thoracic aorta	UBERON:0002345	91.47	gold quality
myometrium	UBERON:0001296	90.55	gold quality
tendon of biceps brachii	UBERON:0008188	90.21	gold quality
right coronary artery	UBERON:0001625	89.48	gold quality
ascending aorta	UBERON:0001496	88.98	gold quality
thoracic aorta	UBERON:0001515	88.92	gold quality
endometrium	UBERON:0001295	87.74	gold quality
uterus	UBERON:0000995	87.62	gold quality
skin of hip	UBERON:0001554	87.05	gold quality
aorta	UBERON:0000947	86.24	gold quality
endocervix	UBERON:0000458	85.29	gold quality
left coronary artery	UBERON:0001626	85.04	gold quality
tibial artery	UBERON:0007610	84.52	gold quality
popliteal artery	UBERON:0002250	84.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.35	gold quality
visceral pleura	UBERON:0002401	83.91	gold quality
ectocervix	UBERON:0012249	83.73	gold quality
coronary artery	UBERON:0001621	82.98	gold quality
cauda epididymis	UBERON:0004360	82.49	gold quality
tendon	UBERON:0000043	81.98	gold quality
hindlimb stylopod muscle	UBERON:0004252	81.65	gold quality
lower esophagus muscularis layer	UBERON:0035833	81.28	gold quality
lower esophagus	UBERON:0013473	81.26	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-ENAD-27	yes	939.53
E-MTAB-5061	yes	754.32
E-GEOD-81608	yes	650.02
E-GEOD-75688	yes	592.00
E-HCAD-31	yes	48.79
E-MTAB-8410	yes	37.21
E-GEOD-81547	yes	29.32
E-MTAB-10287	yes	18.79
E-GEOD-83139	yes	13.81
E-ANND-3	yes	11.83
E-CURD-112	yes	6.18

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, ETV6, FOS, IRF8, TWIST1

miRNA regulators (miRDB)

29 targeting FAP, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-1911-5P	98.92	67.53	325
HSA-MIR-629-5P	98.78	68.72	1032
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-6072	98.00	66.47	804
HSA-MIR-193B-5P	97.91	65.88	837
HSA-MIR-125A-3P	97.04	66.92	902
HSA-MIR-5194	96.77	63.91	1021
HSA-MIR-552-3P	96.68	64.12	1026
HSA-MIR-345-5P	96.40	66.43	663
HSA-MIR-6738-5P	96.33	63.61	815
HSA-MIR-6891-3P	95.80	65.76	683
HSA-MIR-1914-3P	95.07	63.37	762

Literature-anchored findings (GeneRIF, showing 40)

• expression of the seprase-DPPIV complex is restricted to migratory cells involved in wound closure (PMID:12023964)
• seprase and the urokinase plasminogen activator receptor (uPAR), co-localize in the plasma membrane of LOX malignant melanoma cells (PMID:12376466)
• This protein and collagen are intrahepatically expressed in hepatitis C infection. (PMID:12675244)
• Seprase may be an early marker of tumor invasion in squamous lesions of the uterine cervix. (PMID:12926053)
• An abundant expression of seprase in colorectal cancer tissue is associated with lymph node metastasis. (PMID:12963128)
• Seprase may contribute to the pathogenesis of breast cancer by promoting growth of the primary tumor and by facilitating the growth of breast cancer cells in metastases at other sites of the body (PMID:14524536)
• These results suggested that there is a difference in seprase expression between intestinal- and diffuse-type gastric cancer; this difference may reflect distinct biological features of these types of cancer (PMID:14707457)
• the enzymatic activity of fibroblast activation protein plays an important role in the promotion of tumor growth (PMID:15767544)
• molecular determinants responsible for the substrate specificity and endopeptidase activity (PMID:15809306)
• analysis of response of CD4(+) and CD8(+) T-cells to the human stromal antigen, fibroblast activation protein (PMID:16061874)
• FAP has important nonenzymatic functions that in chronic liver injury may facilitate tissue remodeling through FAP-mediated enhancement of HSC cell adhesion, migration, and apoptosis (PMID:16175601)
• Increased expression of seprase is associated with lymph node metastasis in colorectal cancer (PMID:16196122)
• Circulating antiplasmin-cleaving enzyme (APCE) has a role in fibrinolysis and appears structurally similar to fibroblast activation protein (APCE). (PMID:16223769)
• Conversion of FAP to the more easily fibrin-incorporable form, Asn-alpha2AP, may increase plasmin inhibition within fibrin (PMID:16223769)
• fibroblast activation protein protease inhibition is based on dipeptide substrate specificity (PMID:16410248)
• FAP required substrates with Pro at P(1) and Gly or d-amino acids at P(2) and preferred small, uncharged amino acids at P(3), but tolerated most amino acids at P(4), P(1)(’) and P(2)(’). (PMID:16480718)
• Expression of active FAPalpha on chondrocyte membrane and elevated levels in cartilage from osteoarthritis patients. May have important pathological role in cartilage turnover prevalent in arthritic diseases. (PMID:16507127)
• overexpression in HEK293 cells reduced cell adhesion, migration and invasion on ECM components, increased proliferation and promoted apoptosis, independently of enzyme activity (PMID:16700525)
• The reported type 1 diabetes association is from a linkage disequilibrium region including three candidate genes, FAP, IFIH1 and GCA. (PMID:18071670)
• The substrate specificity of FAP was identified by mapping of cleavage sites within collagen I, and peptides synthesized based on these sites showed similar Km values for high and low ranked substrates, but the kcat values differed up to 100-fold. (PMID:18095711)
• FAP-alpha expression in metaplastic, dysplastic, and esophageal cancer tissue is associated with neoplastic progression of esophageal lesions. (PMID:18570153)
• Fibroblast activation protein is highly expressed in pancreatic adenocarcinoma, with greatest expression immediately adjacent to tumor. Higher FAP expression is associated with worse clinical outcome. (PMID:18665076)
• seprase may have a role in promotion of an invasive phenotype by collagenous matrices in ovarian tumor cells (PMID:18823010)
• This study examines FAP’s function in vitro by assaying the proliferation, migration and invasion of ovarian cancer cell line HO-8910PM.. (PMID:19747910)
• data suggest that FAP and DPP-IV are consistently expressed in bone and soft tissue tumour cells that are histogenetically related to activated fibroblasts and/or myofibroblasts, irrespective of their malignancy. (PMID:19817894)
• DPP8 and DPP9 prevail over canonical DPP-IV/CD26 and FAPalpha in all examined meningioma patients (PMID:20043068)
• central role for the serine protease activity of FAP and DPP-4/CD26 in protecting articular cartilage against invasion by synovial fibroblasts in rheumatoid arthritis (PMID:20155839)
• Suggest fibroblast-activation protein as a histologic adjunct in confidently differentiating morpheaform/infiltrative basal cell carcinoma from desmoplastic trichoepithelioma. (PMID:20711172)
• FAP is overexpressed in Crohn disease strictures (PMID:20806341)
• role in the invasive behavior of keloids (PMID:20872224)
• Neuropeptide Y, B-type natriuretic peptide, substance P and peptide YY were the most efficiently hydrolysed substrates and the first hormone substrates of FAP to be identified. (PMID:21314817)
• These experiments suggest a functional association between UVR and FAP-alpha expression that UVR of malignant melanoma converts fibroblasts into FAP-alpha expressing and ECM degrading fibroblasts thus facilitating invasion and migration. (PMID:21491083)
• the associated dynamics of DPP-IV and FAP gene expression in glioblastoma cells further argues in favor of their putative joint involvement in biological processes (PMID:21526345)
• FAP remodels the ECM by modulating protein levels & increasing fibronectin levels & collagen fiber organization. FAP-dependent architectural/compositional ECM alterations promote tumor invasion along characteristic parallel fiber orientations. (PMID:21668992)
• immunostaining with FAP-alpha and Calponin can serve as a novel marker for pathologically diagnosing whether ductal carcinoma in situ has microinvasion. (PMID:22067528)
• Studies indicate that the identification of fibroblast activation protein alpha (FAP) as a target selectively expressed on carcinoma-associated fibroblasts led to intensive efforts to exploit this novel cellular target for clinical benefit. (PMID:22323494)
• Data show that fibroblast activation protein is highly expressed in carcinoma cells and fibroblasts in PDAC tissues, and its expression is associated with desmoplasia and worse prognosis. (PMID:22371645)
• Strong FAPalpha and TGF-beta1 expressions were detected in myocardial cytoplasm in both acute and recurrent myocardial infarction groups. (PMID:22435331)
• REVIEW: key modulator of the microenvironment in multiple pathologies (PMID:22608558)
• FAP is an important regulator of the microenvironment in tumor formation (PMID:22614695)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fap	ENSMUSG00000000392
rattus_norvegicus	Fap	ENSRNOG00000005679
caenorhabditis_elegans		WBGENE00001055

Paralogs (6): DPP8 (ENSG00000074603), DPP6 (ENSG00000130226), DPP9 (ENSG00000142002), APEH (ENSG00000164062), DPP10 (ENSG00000175497), DPP4 (ENSG00000197635)

Protein

Protein identifiers

Prolyl endopeptidase FAP — Q12884 (reviewed: Q12884)

Alternative names: 170 kDa melanoma membrane-bound gelatinase, Dipeptidyl peptidase FAP, Fibroblast activation protein alpha, Gelatine degradation protease FAP, Integral membrane serine protease, Post-proline cleaving enzyme, Serine integral membrane protease, Surface-expressed protease

All UniProt accessions (6): Q12884, B4DLR2, C9J131, F8WF29, H0YG61, H7C4D9

UniProt curated annotations — full annotation on UniProt →

Function. Cell surface glycoprotein serine protease that participates in extracellular matrix degradation and involved in many cellular processes including tissue remodeling, fibrosis, wound healing, inflammation and tumor growth. Both plasma membrane and soluble forms exhibit post-proline cleaving endopeptidase activity, with a marked preference for Ala/Ser-Gly-Pro-Ser/Asn/Ala consensus sequences, on substrate such as alpha-2-antiplasmin SERPINF2 and SPRY2. Degrade also gelatin, heat-denatured type I collagen, but not native collagen type I and IV, vitronectin, tenascin, laminin, fibronectin, fibrin or casein. Also has dipeptidyl peptidase activity, exhibiting the ability to hydrolyze the prolyl bond two residues from the N-terminus of synthetic dipeptide substrates provided that the penultimate residue is proline, with a preference for Ala-Pro, Ile-Pro, Gly-Pro, Arg-Pro and Pro-Pro. Natural neuropeptide hormones for dipeptidyl peptidase are the neuropeptide Y (NPY), peptide YY (PYY), substance P (TAC1) and brain natriuretic peptide 32 (NPPB). The plasma membrane form, in association with either DPP4, PLAUR or integrins, is involved in the pericellular proteolysis of the extracellular matrix (ECM), and hence promotes cell adhesion, migration and invasion through the ECM. Plays a role in tissue remodeling during development and wound healing. Participates in the cell invasiveness towards the ECM in malignant melanoma cancers. Enhances tumor growth progression by increasing angiogenesis, collagen fiber degradation and apoptosis and by reducing antitumor response of the immune system. Promotes glioma cell invasion through the brain parenchyma by degrading the proteoglycan brevican. Acts as a tumor suppressor in melanocytic cells through regulation of cell proliferation and survival in a serine protease activity-independent manner.

Subunit / interactions. Homodimer; homodimerization is required for activity of both plasma membrane and soluble forms. The monomer is inactive. Heterodimer with DPP4. Interacts with PLAUR; the interaction occurs at the cell surface of invadopodia membranes. Interacts with ITGB1. Interacts with ITGA3. Associates with integrin alpha-3/beta-1; the association occurs in a collagen-dependent manner at the cell surface of invadopodia membranes.

Subcellular location. Cell surface. Cell membrane. Cell projection. Lamellipodium membrane. Invadopodium membrane. Ruffle membrane. Membrane Secreted Cytoplasm.

Tissue specificity. Expressed in adipose tissue. Expressed in the dermal fibroblasts in the fetal skin. Expressed in the granulation tissue of healing wounds and on reactive stromal fibroblast in epithelial cancers. Expressed in activated fibroblast-like synoviocytes from inflamed synovial tissues. Expressed in activated hepatic stellate cells (HSC) and myofibroblasts from cirrhotic liver, but not detected in normal liver. Expressed in glioma cells (at protein level). Expressed in glioblastomas and glioma cells. Isoform 1 and isoform 2 are expressed in melanoma, carcinoma and fibroblast cell lines.

Post-translational modifications. N-glycosylated. The N-terminus may be blocked.

Activity regulation. Gelatinase activity is inhibited by serine-protease inhibitors, such as phenylmethylsulfonyl fluoride (PMSF), 4-(2-aminoethyl)-benzenesulfonyl fluoride hydrochloride (AEBSF), 4-amidino phenylsulfonyl fluoride (APSF) and diisopropyl fluorophosphate (DFP), N-ethylmaleimide (NEM) and phenylmethylsulfonyl fluoride (PMSF). Dipeptidyl peptidase activity is inhibited by 2,2’-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), diisopropylfluorophosphate (DFP). Prolyl endopeptidase activity is inhibited by the boronic acid peptide Ac-Gly-BoroPro, Ac-Gly-Pro-chloromethyl ketone and Thr-Ser-Gly-chloromethyl ketone.

Induction. In fibroblasts at times and sites of tissue remodeling during development, tissue repair and carcinogenesis. Up-regulated upon tumor stem cell differentiation. Up-regulated by transforming growth factor-beta, 12-O-tetradecanoyl phorbol-13-acetate and retinoids.

Miscellaneous. Major isoform. Upstream open reading frames ORF(s)-containing region inhibits the translation of its downstream ORF.

Similarity. Belongs to the peptidase S9B family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q12884-1	1, L, seprase-I	yes
Q12884-2	2, S, Truncated, seprase-s

RefSeq proteins (2): NP_001278736, NP_004451* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001375	Peptidase_S9_cat	Domain
IPR002469	Peptidase_S9B_N	Domain
IPR002471	Pept_S9_AS	Active_site
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR050278	Serine_Prot_S9B/DPPIV	Family

Pfam: PF00326, PF00930

Enzyme classification (BRENDA):

• EC 3.4.21.B28 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

UniProt features (120 total): strand 55, helix 20, mutagenesis site 10, turn 9, glycosylation site 6, disulfide bond 4, sequence conflict 3, active site 3, chain 2, topological domain 2, binding site 2, site 1, splice variant 1, sequence variant 1, transmembrane region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1Z68	X-RAY DIFFRACTION	2.6
9DVQ	ELECTRON MICROSCOPY	2.7
9DVR	ELECTRON MICROSCOPY	2.7
6Y0F	X-RAY DIFFRACTION	2.92

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12884-F1	95.72	0.94

Antibody-complex structures (SAbDab): 2 — 9DVQ, 9DVR

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (4): 23–24 (cleavage); 624 (charge relay system); 702 (charge relay system); 734 (charge relay system)

Ligand- & substrate-binding residues (2): 203; 204

Disulfide bonds (4): 321–332, 438–441, 448–466, 643–755

Glycosylation sites (6): 49, 92, 99, 227, 314, 679

Mutagenesis-validated functional residues (10):

Position	Phenotype
123	reduces dipeptidyl peptidase and endopeptidase activities.
203	reduces dipeptidyl peptidase and endopeptidase activities. does not inhibit cell adhesion, migration and invasion. inhib
204	reduces dipeptidyl peptidase and endopeptidase activities. does not inhibit cell adhesion, migration and invasion. inhib
624	reduces dipeptidyl peptidase and gelatinolytic activities. does not inhibit cell adhesion, migration and invasion.
656	reduces dipeptidyl peptidase and endopeptidase activities.
657	inhibits endopeptidase activity. increases dipeptidyl peptidase activity.
657	reduces dipeptidyl peptidase and endopeptidase activities.
657	inhibits endopeptidase activity. no change in dipeptidyl peptidase activity.
657	strongly reduces endopeptidase activity. no change in dipeptidyl peptidase activity.
704	reduces dipeptidyl peptidase and endopeptidase activities.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 287 (showing top): MODULE_172, TSENG_IRS1_TARGETS_UP, GOBP_REGULATION_OF_WOUND_HEALING, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_REGULATION_OF_COAGULATION, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOCC_CELL_SURFACE, MODULE_128, GNF2_PTX3, TAL1ALPHAE47_01, GOCC_RUFFLE, GOBP_REGULATION_OF_EXTRACELLULAR_MATRIX_ORGANIZATION, CEBPB_01, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_COAGULATION

GO Biological Process (15): angiogenesis (GO:0001525), proteolysis (GO:0006508), cell adhesion (GO:0007155), regulation of collagen catabolic process (GO:0010710), negative regulation of extracellular matrix disassembly (GO:0010716), endothelial cell migration (GO:0043542), obsolete proteolysis involved in protein catabolic process (GO:0051603), regulation of cell cycle (GO:0051726), regulation of fibrinolysis (GO:0051917), negative regulation of cell proliferation involved in contact inhibition (GO:0060244), melanocyte proliferation (GO:0097325), positive regulation of execution phase of apoptosis (GO:1900119), melanocyte apoptotic process (GO:1902362), negative regulation of extracellular matrix organization (GO:1903054), apoptotic process (GO:0006915)

GO Molecular Function (11): protease binding (GO:0002020), endopeptidase activity (GO:0004175), serine-type endopeptidase activity (GO:0004252), integrin binding (GO:0005178), peptidase activity (GO:0008233), serine-type peptidase activity (GO:0008236), dipeptidyl-peptidase activity (GO:0008239), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (15): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), plasma membrane (GO:0005886), focal adhesion (GO:0005925), cell surface (GO:0009986), membrane (GO:0016020), lamellipodium (GO:0030027), lamellipodium membrane (GO:0031258), ruffle membrane (GO:0032587), apical part of cell (GO:0045177), basal part of cell (GO:0045178), peptidase complex (GO:1905368), extracellular region (GO:0005576), cell projection (GO:0042995), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
execution phase of apoptosis	2
peptidase activity	2
cell projection membrane	2
leading edge membrane	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
protein metabolic process	1
cellular process	1
regulation of catabolic process	1
regulation of collagen metabolic process	1
collagen catabolic process	1
regulation of extracellular matrix disassembly	1
extracellular matrix disassembly	1
negative regulation of extracellular matrix organization	1
cell migration	1
cell cycle	1
regulation of cellular process	1
regulation of blood coagulation	1
fibrinolysis	1
negative regulation of cell population proliferation	1
contact inhibition	1
epithelial cell proliferation	1
positive regulation of apoptotic process	1
regulation of execution phase of apoptosis	1
apoptotic process	1
extracellular matrix organization	1
negative regulation of cellular component organization	1
regulation of extracellular matrix organization	1
programmed cell death	1
apoptotic signaling pathway	1
enzyme binding	1
endopeptidase activity	1
serine-type peptidase activity	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
serine hydrolase activity	1

Protein interactions and networks

STRING

1540 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAP	ADA	P00813	849
FAP	DPP7	Q9UHL4	680
FAP	GCG	P01275	668
FAP	INS	P01308	661
FAP	PREP	P48147	656
FAP	FN1	P02751	643
FAP	GLP1R	P43220	620
FAP	PTPRC	P08575	584
FAP	PLAU	P00749	576
FAP	PYY	P10082	569
FAP	SPP1	P10451	523
FAP	GIP	P09681	515
FAP	ITGB1	P05556	507
FAP	IL2	P01585	505
FAP	CXCL12	P48061	495

IntAct

30 interactions, top by confidence:

A	B	Type	Score
OSM	IL6ST	psi-mi:“MI:0914”(association)	0.760
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
GCG	FAP	psi-mi:“MI:0194”(cleavage reaction)	0.440
FAP	VIP	psi-mi:“MI:0194”(cleavage reaction)	0.440
FAP	GHRH	psi-mi:“MI:0194”(cleavage reaction)	0.440
PYY	FAP	psi-mi:“MI:0194”(cleavage reaction)	0.440
NPPB	FAP	psi-mi:“MI:0194”(cleavage reaction)	0.440
NPY	FAP	psi-mi:“MI:0194”(cleavage reaction)	0.440
FAP	TAC1	psi-mi:“MI:0194”(cleavage reaction)	0.440
GIP	FAP	psi-mi:“MI:0194”(cleavage reaction)	0.440
FAP	GCG	psi-mi:“MI:0194”(cleavage reaction)	0.440
FAP	ADCYAP1	psi-mi:“MI:0194”(cleavage reaction)	0.440
FAP	CABCOCO1	psi-mi:“MI:0915”(physical association)	0.400
	NPC1	psi-mi:“MI:0914”(association)	0.350
CDKN2D	HBQ1	psi-mi:“MI:0914”(association)	0.350
CLGN	TMEM131L	psi-mi:“MI:0914”(association)	0.350
DDX1	HERC2	psi-mi:“MI:0914”(association)	0.350
DLK1	PLPP3	psi-mi:“MI:0914”(association)	0.350
LGALS3	SDCBP	psi-mi:“MI:0914”(association)	0.350
RWDD4	CRP	psi-mi:“MI:0914”(association)	0.350
SCN3B	NBAS	psi-mi:“MI:0914”(association)	0.350
ATF3	ILVBL	psi-mi:“MI:0914”(association)	0.350
ATF1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CEBPD	ESYT2	psi-mi:“MI:0914”(association)	0.350
PPARA	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (33): CORO1C (Co-fractionation), ADA (Affinity Capture-MS), CAV1 (Affinity Capture-MS), DPP4 (Affinity Capture-MS), ERLIN2 (Affinity Capture-MS), STOM (Affinity Capture-MS), PHB (Affinity Capture-MS), PHB2 (Affinity Capture-MS), MSRB1 (Affinity Capture-MS), RBM4 (Affinity Capture-MS), THY1 (Affinity Capture-MS), TMEM109 (Affinity Capture-MS), ADA (Affinity Capture-Western), CAV1 (Affinity Capture-Western), DPP4 (Affinity Capture-Western)

ESM2 similar proteins: A0A0C1E1D0, A0A1L9WUM2, A0A1Q3EPF5, A0A4S8L6U5, A0S5V9, A1CHP1, A1CX29, A5D7B7, A7UKV8, B0Y6C5, B1A4F7, B2D0J4, B6V868, B8N970, C5FJE3, C9K7B8, D4APE2, D4CZ59, E2JFG1, E2JFG2, H2E7Q7, H2E7Q8, O14073, P0DRB8, P14740, P22411, P27487, P28843, P42658, P46101, P78875, P81425, P97321, P9WEN5, Q09541, Q12884, Q2UH35, Q4WAZ0, Q4WPH9, Q5AV79

Diamond homologs: A0S5V9, A1CHP1, A1CJQ1, A1CX29, A1D7R6, A2QEK7, A4QYQ5, A5D7B7, A6RBI0, A6SL49, A7EQZ1, A7UKV8, B0XYK8, B0Y6C5, B1A4F7, B2A951, B2D0J4, B2WC36, B6HFS8, B6QVW4, B6V868, B8MTH6, B8N076, B8N970, C0NUQ8, C0S7H1, C1FZL3, C1GT79, C4JHY5, C5FJE3, C5FYZ3, C5GVF3, C5JC30, C5P334, C6HRC7, C7YYG9, C9SJ15, D1Z9B4, D4APE2, D4AQT0

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
EGR1	“up-regulates quantity by expression”	FAP	“transcriptional regulation”
TWIST1	“up-regulates quantity by expression”	FAP	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Glucagon-type ligand receptors	5	61.8×	2e-06
G alpha (s) signalling events	5	13.1×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
neuropeptide signaling pathway	5	26.9×	2e-04
adenylate cyclase-activating G protein-coupled receptor signaling pathway	5	17.7×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

126 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	92
Likely benign	6
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

4401 predictions. Top by Δscore:

Variant	Effect	Δscore
2:162171081:C:CC	acceptor_gain	1.0000
2:162171421:T:TC	acceptor_gain	1.0000
2:162173148:CCAT:C	donor_gain	1.0000
2:162173220:TT:T	acceptor_gain	1.0000
2:162173222:C:CC	acceptor_gain	1.0000
2:162173786:CG:C	acceptor_gain	1.0000
2:162173788:C:CC	acceptor_gain	1.0000
2:162174967:C:CC	acceptor_gain	1.0000
2:162188296:T:C	acceptor_gain	1.0000
2:162189654:A:AC	donor_gain	1.0000
2:162189655:C:CC	donor_gain	1.0000
2:162189655:CTA:C	donor_gain	1.0000
2:162189670:T:TA	donor_gain	1.0000
2:162189681:AATTT:A	donor_gain	1.0000
2:162189752:TTT:T	acceptor_gain	1.0000
2:162189755:C:CC	acceptor_gain	1.0000
2:162194019:TGG:T	donor_gain	1.0000
2:162195551:G:C	donor_gain	1.0000
2:162198877:TAATT:T	acceptor_gain	1.0000
2:162198880:TT:T	acceptor_gain	1.0000
2:162198881:TCTA:T	acceptor_loss	1.0000
2:162198882:C:CC	acceptor_gain	1.0000
2:162198882:C:T	acceptor_loss	1.0000
2:162198883:T:A	acceptor_loss	1.0000
2:162200565:CCTGT:C	donor_loss	1.0000
2:162200617:AAC:A	acceptor_gain	1.0000
2:162200618:AC:A	acceptor_gain	1.0000
2:162200619:CC:C	acceptor_gain	1.0000
2:162200620:C:CC	acceptor_gain	1.0000
2:162214071:TCA:T	acceptor_gain	1.0000

AlphaMissense

5000 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:162173152:C:G	D702H	0.997
2:162200607:G:C	S412R	0.997
2:162200607:G:T	S412R	0.997
2:162200609:T:G	S412R	0.997
2:162214046:C:A	W298C	0.997
2:162214046:C:G	W298C	0.997
2:162214048:A:G	W298R	0.997
2:162214048:A:T	W298R	0.997
2:162218108:A:G	W214R	0.997
2:162218108:A:T	W214R	0.997
2:162173151:T:A	D702V	0.996
2:162173172:A:G	L695P	0.996
2:162198763:A:G	C466R	0.996
2:162198761:G:C	C466W	0.995
2:162200615:A:C	Y410D	0.995
2:162209963:A:G	W346R	0.995
2:162209963:A:T	W346R	0.995
2:162219876:A:G	W155R	0.995
2:162219876:A:T	W155R	0.995
2:162171080:A:G	W728R	0.994
2:162171080:A:T	W728R	0.994
2:162172842:A:G	L717P	0.994
2:162174900:C:G	A646P	0.994
2:162214032:C:G	R303P	0.994
2:162219075:A:G	W199R	0.994
2:162219075:A:T	W199R	0.994
2:162219086:C:T	G195E	0.994
2:162223639:C:G	A128P	0.994
2:162226530:C:A	W61C	0.994
2:162226530:C:G	W61C	0.994

dbSNP variants (sampled 300 via entrez): RS1000079893 (2:162202561 T>G), RS1000097199 (2:162226857 T>C), RS1000116460 (2:162206926 T>C,G), RS1000124096 (2:162176048 G>A), RS1000127007 (2:162226753 C>A,T), RS1000172513 (2:162207770 G>C), RS1000290201 (2:162213503 T>C), RS1000320781 (2:162213663 G>A), RS1000387405 (2:162179786 C>A), RS1000446063 (2:162213419 A>C,G), RS1000498185 (2:162237386 A>C,G), RS1000499053 (2:162226983 T>C), RS1000522353 (2:162195778 A>G,T), RS1000593673 (2:162207274 G>A), RS1000663641 (2:162215389 G>A)

Disease associations

OMIM: gene MIM:600403 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002740_53	Inflammatory skin disease	2.000000e-12
GCST005537_164	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	3.000000e-13
GCST005752_118	Systemic lupus erythematosus	5.000000e-12
GCST005984_6	Glomerular filtration rate	5.000000e-08
GCST006921_12	Regular attendance at a pub or social club	2.000000e-08
GCST007344_62	Estimated glomerular filtration rate	2.000000e-08
GCST007932_41	Medication use (thyroid preparations)	2.000000e-13
GCST010866_40	Coronary artery disease	4.000000e-08
GCST011956_69	Systemic lupus erythematosus	3.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009592	social interaction measurement
EFO:0009933	Thyroid preparation use measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4683 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

14 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 119,675 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1422	SITAGLIPTIN	4	26,582
CHEMBL142703	VILDAGLIPTIN	4	20,312
CHEMBL1486	TENOFOVIR DISOPROXIL FUMARATE	4	13,116
CHEMBL1538	TENOFOVIR DISOPROXIL	4	7,909
CHEMBL1929396	ANAGLIPTIN	4	1,091
CHEMBL237500	LINAGLIPTIN	4	5,282
CHEMBL454446	CEFDITOREN PIVOXIL	4	3,185
CHEMBL515387	GOSOGLIPTIN	4	785
CHEMBL922	ADEFOVIR DIPIVOXIL	4	27,632
CHEMBL2107486	TEBIPENEM PIVOXIL	3	345
CHEMBL3182314	SIVELESTAT SODIUM	3	35
CHEMBL4296719	DUTOGLIPTIN	3	1,373
CHEMBL67279	TALABOSTAT	3	10,259
CHEMBL76688	SIVELESTAT	3	1,769

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — S9: Prolyl oligopeptidase

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
AZD2389	Inhibition	9.44	pIC50
compound 9 [PMID: 20718420]	Inhibition	7.72	pIC50
ARI-3099	Inhibition	7.44	pIC50

Binding affinities (BindingDB)

172 measured of 404 human assays (405 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
US20250177582, Compound 28	IC50	0.03 nM	US-20250177582: HIGH-AFFINITY LIGANDS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED DELIVERY APPLICATIONS
US20250177582, Compound 26	IC50	0.075 nM	US-20250177582: HIGH-AFFINITY LIGANDS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED DELIVERY APPLICATIONS
1.3.8.1 Synthesis of Compound 11	IC50	0.156 nM	US-20250177582: HIGH-AFFINITY LIGANDS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED DELIVERY APPLICATIONS
US20250177582, Compound 14	IC50	0.353 nM	US-20250177582: HIGH-AFFINITY LIGANDS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED DELIVERY APPLICATIONS
US20250177582, Compound 9	IC50	0.439 nM	US-20250177582: HIGH-AFFINITY LIGANDS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED DELIVERY APPLICATIONS
US20250177582, Compound 17	IC50	0.697 nM	US-20250177582: HIGH-AFFINITY LIGANDS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED DELIVERY APPLICATIONS
US20250177582, Compound 19	IC50	0.991 nM	US-20250177582: HIGH-AFFINITY LIGANDS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED DELIVERY APPLICATIONS
US20250177582, Compound 27	IC50	1.02 nM	US-20250177582: HIGH-AFFINITY LIGANDS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED DELIVERY APPLICATIONS
5-[[2-chloro-4-fluoro-5-(3-fluoro-2-pyridinyl)benzoyl]amino]-1-phenyl-N-(pyridazin-3-ylmethyl)pyrazole-3-carboxamide	IC50	1.1 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
US20250177582, Compound 12	IC50	1.29 nM	US-20250177582: HIGH-AFFINITY LIGANDS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED DELIVERY APPLICATIONS
Lutetium(III) 2,2’,2″-(10-(2-(((S)-1-((5-((4-((2-((2R,4S)-2-borono-4-hydroxypyrrolidin-1-yl)-2-oxoethyl)carbamoyl)benzyl)(methyl)amino)-5-oxopentyl)amino)-5-guanidino-1-oxopentan-2-yl)amino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate	IC50	1.5 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
US20250177582, Compound 18	IC50	1.55 nM	US-20250177582: HIGH-AFFINITY LIGANDS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED DELIVERY APPLICATIONS
5-[(2-chloro-4-fluoro-5-pyridin-2-ylbenzoyl)amino]-N-[2-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl]-1-phenylpyrazole-3-carboxamide	IC50	1.6 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[[2,4-dichloro-5-(5-fluoro-2-pyridinyl)benzoyl]amino]-N-(oxetan-3-yl)-1-phenylpyrazole-3-carboxamide	IC50	1.6 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[[2,4-dichloro-5-(5-fluoro-2-pyridinyl)benzoyl]amino]-N-[(3R,4S)-3-hydroxyoxan-4-yl]-1-phenylpyrazole-3-carboxamide	IC50	1.6 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[[2-chloro-4-fluoro-5-(3-fluoro-2-pyridinyl)benzoyl]amino]-N-[(2R)-1-hydroxypropan-2-yl]-1-phenylpyrazole-3-carboxamide	IC50	1.6 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[[2-chloro-4-fluoro-5-(3-fluoro-2-pyridinyl)benzoyl]amino]-N-[(5-methyl-1H-1,2,4-triazol-3-yl)methyl]-1-phenylpyrazole-3-carboxamide	IC50	1.6 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
US20250177582, Compound 16	IC50	1.66 nM	US-20250177582: HIGH-AFFINITY LIGANDS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED DELIVERY APPLICATIONS
5-[[2,4-dichloro-5-(5-fluoro-2-pyridinyl)benzoyl]amino]-N-(3-methylpyrazolidin-4-yl)-1-phenylpyrazole-3-carboxamide	IC50	1.7 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[[2,4-dichloro-5-(5-fluoro-2-pyridinyl)benzoyl]amino]-N-(1-methylazetidin-3-yl)-1-phenylpyrazole-3-carboxamide	IC50	1.7 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[[2-chloro-4-fluoro-5-(3-fluoro-2-pyridinyl)benzoyl]amino]-N-[3-(hydroxymethyl)oxetan-3-yl]-1-phenylpyrazole-3-carboxamide	IC50	1.7 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[[2-chloro-4-fluoro-5-(3-fluoro-2-pyridinyl)benzoyl]amino]-N-(3-methyloxetan-3-yl)-1-phenylpyrazole-3-carboxamide	IC50	1.8 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
2-chloro-4-fluoro-5-(3-fluoro-2-pyridinyl)-N-[3-(3-hydroxyazetidine-1-carbonyl)-1-phenylpyrazol-5-yl]benzamide	IC50	1.8 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
N-[3-(4-acetylpiperazine-1-carbonyl)-1-phenylpyrazol-5-yl]-2-chloro-4-fluoro-5-pyridin-2-ylbenzamide	IC50	1.9 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[[2-chloro-4-fluoro-5-(3-fluoro-2-pyridinyl)benzoyl]amino]-N-(1-methylazetidin-3-yl)-1-phenylpyrazole-3-carboxamide	IC50	1.9 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[[2-chloro-4-fluoro-5-(3-fluoro-2-pyridinyl)benzoyl]amino]-N-[(1-methylpyrazol-4-yl)methyl]-1-phenylpyrazole-3-carboxamide	IC50	1.9 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[[2-chloro-4-fluoro-5-(3-fluoro-2-pyridinyl)benzoyl]amino]-N-[(3R)-oxolan-3-yl]-1-phenylpyrazole-3-carboxamide	IC50	1.9 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[[2-chloro-4-fluoro-5-(3-fluoro-2-pyridinyl)benzoyl]amino]-N-(3-hydroxycyclobutyl)-1-phenylpyrazole-3-carboxamide	IC50	2 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[(2-chloro-4-fluoro-5-pyridin-2-ylbenzoyl)amino]-N-[(1-methyl-5-oxopyrrolidin-3-yl)methyl]-1-phenylpyrazole-3-carboxamide	IC50	2.1 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[[2,4-dichloro-5-(5-fluoro-2-pyridinyl)benzoyl]amino]-N-(4-hydroxy-4-methylcyclohexyl)-1-phenylpyrazole-3-carboxamide	IC50	2.1 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[[2,4-dichloro-5-(5-fluoro-2-pyridinyl)benzoyl]amino]-N-[(3S,4R)-4-hydroxyoxolan-3-yl]-1-phenylpyrazole-3-carboxamide	IC50	2.1 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
2-chloro-N-[3-[4-(dimethylamino)piperidine-1-carbonyl]-1-phenylpyrazol-5-yl]-4-fluoro-5-pyridin-2-ylbenzamide	IC50	2.2 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
N-[3-[2,2-bis(hydroxymethyl)pyrrolidine-1-carbonyl]-1-phenylpyrazol-5-yl]-2-chloro-4-fluoro-5-pyridin-2-ylbenzamide	IC50	2.2 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[(2-chloro-4-fluoro-5-pyridin-2-ylbenzoyl)amino]-N-[4-(dimethylamino)-2-hydroxybutyl]-1-phenylpyrazole-3-carboxamide	IC50	2.2 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
N-(2-amino-2-oxoethyl)-5-[[2,4-dichloro-5-(5-fluoro-2-pyridinyl)benzoyl]amino]-1-phenylpyrazole-3-carboxamide	IC50	2.2 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[[2,4-dichloro-5-(5-fluoro-2-pyridinyl)benzoyl]amino]-N-(3-hydroxycyclobutyl)-1-phenylpyrazole-3-carboxamide	IC50	2.2 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[[2,4-dichloro-5-(5-fluoro-2-pyridinyl)benzoyl]amino]-N-(1,3-oxazol-2-ylmethyl)-1-phenylpyrazole-3-carboxamide	IC50	2.3 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[[2,4-dichloro-5-(5-fluoro-2-pyridinyl)benzoyl]amino]-N-[(2R)-1-hydroxy-3-methoxypropan-2-yl]-1-phenylpyrazole-3-carboxamide	IC50	2.3 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[[2,4-dichloro-5-(5-fluoro-2-pyridinyl)benzoyl]amino]-1-phenyl-N-(pyrimidin-2-ylmethyl)pyrazole-3-carboxamide	IC50	2.3 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[[2,4-dichloro-5-(5-fluoro-2-pyridinyl)benzoyl]amino]-N-[(2S)-2-hydroxypropyl]-1-phenylpyrazole-3-carboxamide	IC50	2.3 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[[2-chloro-4-fluoro-5-(3-fluoro-2-pyridinyl)benzoyl]amino]-1-phenyl-N-(pyridin-2-ylmethyl)pyrazole-3-carboxamide	IC50	2.3 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[[2,4-dichloro-5-(5-fluoro-2-pyridinyl)benzoyl]amino]-1-phenyl-N-(pyrazolidin-3-ylmethyl)pyrazole-3-carboxamide	IC50	2.4 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
N-cyclopropyl-5-[[2,4-dichloro-5-(5-fluoro-2-pyridinyl)benzoyl]amino]-1-phenylpyrazole-3-carboxamide	IC50	2.4 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[[2,4-dichloro-5-(5-fluoro-2-pyridinyl)benzoyl]amino]-N-[(3R,4S)-4-hydroxyoxolan-3-yl]-1-phenylpyrazole-3-carboxamide	IC50	2.4 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[[2,4-dichloro-5-(5-fluoro-2-pyridinyl)benzoyl]amino]-N-(3-hydroxypropyl)-1-phenylpyrazole-3-carboxamide	IC50	2.4 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[[2-chloro-4-fluoro-5-(3-fluoro-2-pyridinyl)benzoyl]amino]-1-phenyl-N-(pyrimidin-2-ylmethyl)pyrazole-3-carboxamide	IC50	2.4 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[[2-chloro-4-fluoro-5-(3-fluoro-2-pyridinyl)benzoyl]amino]-N-[(2S)-1-hydroxypropan-2-yl]-1-phenylpyrazole-3-carboxamide	IC50	2.4 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
N-[2-[(2S)-2-cyano-4,4-difluoropyrrolidin-1-yl]-2-oxoethyl]-6-[3-[4-[6-(dimethylamino)pyridine-3-carbonyl]piperazin-1-yl]propyl-methylamino]quinoline-4-carboxamide	IC50	2.4 nM	US-20250127937: FAP INHIBITOR
5-[(2-chloro-4-fluoro-5-pyridin-2-ylbenzoyl)amino]-N-[2-(4-methylpiperazin-1-yl)ethyl]-1-phenylpyrazole-3-carboxamide	IC50	2.5 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS
5-[(2-chloro-4-fluoro-5-pyridin-2-ylbenzoyl)amino]-N-(2-morpholin-4-yl-2-oxoethyl)-1-phenylpyrazole-3-carboxamide	IC50	2.5 nM	US-20260007787: RADIOPHARMACEUTICAL SMALL MOLECULE INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN FOR TARGETED THERAPY AND DIAGNOSTIC IMAGING OF DESMOPLASTIC TUMORS

ChEMBL bioactivities

370 potent at pChembl≥5 of 461 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.05	IC50	0.089	nM	CHEMBL4877950
9.96	Ki	0.11	nM	CHEMBL6147832
9.89	IC50	0.13	nM	CHEMBL4878759
9.74	IC50	0.18	nM	CHEMBL4864809
9.72	IC50	0.19	nM	CHEMBL4853661
9.72	Ki	0.19	nM	CHEMBL4877950
9.68	IC50	0.21	nM	CHEMBL5569730
9.66	IC50	0.22	nM	CHEMBL4850601
9.64	IC50	0.23	nM	CHEMBL4877950
9.51	IC50	0.31	nM	CHEMBL4876026
9.49	IC50	0.32	nM	CHEMBL4868869
9.49	IC50	0.32	nM	CHEMBL5566777
9.48	IC50	0.33	nM	CHEMBL4850484
9.38	IC50	0.42	nM	CHEMBL4873985
9.38	IC50	0.42	nM	CHEMBL4867484
9.37	IC50	0.43	nM	CHEMBL3233842
9.36	IC50	0.44	nM	CHEMBL4864133
9.34	IC50	0.46	nM	CHEMBL5569691
9.33	IC50	0.47	nM	CHEMBL2333025
9.30	IC50	0.5	nM	CHEMBL4854865
9.28	IC50	0.53	nM	CHEMBL4871602
9.24	IC50	0.58	nM	CHEMBL4855449
9.20	IC50	0.63	nM	CHEMBL4859756
9.20	IC50	0.63	nM	CHEMBL4863249
9.20	IC50	0.63	nM	CHEMBL4868282
9.19	IC50	0.64	nM	CHEMBL4847764
9.17	IC50	0.67	nM	CHEMBL4851238
9.11	IC50	0.77	nM	CHEMBL4855309
9.10	IC50	0.8	nM	CHEMBL5572035
9.10	IC50	0.8	nM	CHEMBL6147832
9.00	IC50	1	nM	CHEMBL4762591
8.96	IC50	1.1	nM	CHEMBL2333023
8.96	IC50	1.1	nM	CHEMBL4846405
8.96	IC50	1.1	nM	CHEMBL4870279
8.96	IC50	1.1	nM	CHEMBL4870593
8.89	Ki	1.3	nM	CHEMBL1243153
8.85	IC50	1.4	nM	CHEMBL5562853
8.82	IC50	1.5	nM	CHEMBL4871573
8.77	IC50	1.7	nM	CHEMBL4861963
8.75	IC50	1.77	nM	CHEMBL5566659
8.74	IC50	1.8	nM	CHEMBL4869146
8.70	IC50	2	nM	CHEMBL4786982
8.68	IC50	2.1	nM	CHEMBL4864489
8.64	IC50	2.3	nM	CHEMBL1243373
8.64	IC50	2.3	nM	CHEMBL3233842
8.57	IC50	2.7	nM	CHEMBL4872140
8.48	IC50	3.3	nM	CHEMBL3233842
8.47	IC50	3.4	nM	CHEMBL2333030
8.47	IC50	3.4	nM	CHEMBL4850470
8.43	IC50	3.7	nM	CHEMBL4863606

PubChem BioAssay actives

306 with measured affinity, of 818 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[2-[(2S)-2-[2-[(3,4-dimethoxyphenyl)methylamino]-2-oxoacetyl]pyrrolidin-1-yl]-2-oxoethyl]quinoline-4-carboxamide	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0001	uM
tert-butyl 2-[[2-oxo-2-[(2S)-1-[2-(quinoline-4-carbonylamino)acetyl]pyrrolidin-2-yl]acetyl]amino]acetate	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0001	uM
2-[4,7-bis(carboxymethyl)-10-[2-[4-[3-[4-[[2-[(2S)-2-cyano-4,4-difluoropyrrolidin-1-yl]-2-oxoethyl]carbamoyl]quinolin-6-yl]oxypropyl]piperazin-1-yl]-2-oxoethyl]-1,4,7,10-tetrazacyclododec-1-yl]acetic acid	2106067: Inhibition of FAP (unknown origin)	ic50	0.0002	uM
N-[2-[(2S)-2-[2-[2-(3,4-dimethoxyphenyl)ethylamino]-2-oxoacetyl]pyrrolidin-1-yl]-2-oxoethyl]quinoline-4-carboxamide	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0002	uM
N-[2-[(2S)-2-[2-[(3-methoxyphenyl)methylamino]-2-oxoacetyl]pyrrolidin-1-yl]-2-oxoethyl]quinoline-4-carboxamide	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0002	uM
N-[2-[(2S)-2-[2-[(4-methoxyphenyl)methylamino]-2-oxoacetyl]pyrrolidin-1-yl]-2-oxoethyl]quinoline-4-carboxamide	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0002	uM
methyl (2S)-5-(benzylamino)-5-oxo-2-[[2-[[2-oxo-2-[(2S)-1-[2-(quinoline-4-carbonylamino)acetyl]pyrrolidin-2-yl]acetyl]amino]acetyl]amino]pentanoate	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0003	uM
N-[2-[(2S)-2-[2-[(2-morpholin-4-yl-2-oxoethyl)amino]-2-oxoacetyl]pyrrolidin-1-yl]-2-oxoethyl]quinoline-4-carboxamide	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0003	uM
methyl (2S)-2-[[2-[[2-oxo-2-[(2S)-1-[2-(quinoline-4-carbonylamino)acetyl]pyrrolidin-2-yl]acetyl]amino]acetyl]amino]-6-(phenylmethoxycarbonylamino)hexanoate	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0003	uM
benzenesulfonate;3-[4-[[2-[(2S)-2-cyano-4,4-difluoropyrrolidin-1-yl]-2-oxoethyl]carbamoyl]quinolin-6-yl]oxypropyl-(fluoromethyl)-dimethylazanium	2106032: Inhibition of FAP (unknown origin) using Z-Gly-Pro-7-amino-4-methylcoumarine as fluorogenic substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins	ic50	0.0003	uM
ethyl 2-[[2-oxo-2-[(2S)-1-[2-(quinoline-4-carbonylamino)acetyl]pyrrolidin-2-yl]acetyl]amino]acetate	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0004	uM
N-[2-[(2S)-2-[2-[(4-fluorophenyl)methylamino]-2-oxoacetyl]pyrrolidin-1-yl]-2-oxoethyl]quinoline-4-carboxamide	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0004	uM
methyl 4-[[2-oxo-2-[(2S)-1-[2-(quinoline-4-carbonylamino)acetyl]pyrrolidin-2-yl]acetyl]amino]benzoate	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0004	uM
N-[2-[(2S)-2-cyano-4,4-difluoropyrrolidin-1-yl]-2-oxoethyl]quinoline-4-carboxamide	2106038: Inhibition of C-terminal His-tagged recombinant human FAP extracellular domain (27 to 760 residues) expressed in Sf9 cells	ic50	0.0004	uM
methyl (2S)-2-[[2-[[2-oxo-2-[(2S)-1-[2-(quinoline-4-carbonylamino)acetyl]pyrrolidin-2-yl]acetyl]amino]acetyl]amino]-3-phenylpropanoate	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0005	uM
N-[2-[(2S)-2-[2-[[2-(tert-butylamino)-2-oxoethyl]amino]-2-oxoacetyl]pyrrolidin-1-yl]-2-oxoethyl]quinoline-4-carboxamide	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0005	uM
N-[2-[(2S)-2-cyano-4,4-difluoropyrrolidin-1-yl]-2-oxoethyl]-6-[[(4S,5R)-5-(fluoromethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]quinoline-4-carboxamide	2106032: Inhibition of FAP (unknown origin) using Z-Gly-Pro-7-amino-4-methylcoumarine as fluorogenic substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins	ic50	0.0005	uM
[(2R)-1-[2-(pyridine-4-carbonylamino)acetyl]pyrrolidin-2-yl]boronic acid	736685: Inhibition of human FAP using Z-Gly-Pro-AMC as substrate preincubated for 10 mins prior to substrate addition by fluorescence assay	ic50	0.0005	uM
N-[2-[(2S)-2-[2-(cyclopropylamino)-2-oxoacetyl]pyrrolidin-1-yl]-2-oxoethyl]quinoline-4-carboxamide	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0006	uM
N-[2-oxo-2-[(2S)-2-[2-oxo-2-(pentylamino)acetyl]pyrrolidin-1-yl]ethyl]quinoline-4-carboxamide	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0006	uM
N-[2-[(2S)-2-[2-[(2,4-dimethylphenyl)methylamino]-2-oxoacetyl]pyrrolidin-1-yl]-2-oxoethyl]quinoline-4-carboxamide	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0006	uM
5-O-benzyl 1-O-methyl (2S)-2-[[2-[[2-oxo-2-[(2S)-1-[2-(quinoline-4-carbonylamino)acetyl]pyrrolidin-2-yl]acetyl]amino]acetyl]amino]pentanedioate	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0006	uM
N-[2-oxo-2-[(2S)-2-[2-oxo-2-(2-phenylethylamino)acetyl]pyrrolidin-1-yl]ethyl]quinoline-4-carboxamide	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0006	uM
N-[2-[(2S)-2-[2-[[2-(hexylamino)-2-oxoethyl]amino]-2-oxoacetyl]pyrrolidin-1-yl]-2-oxoethyl]quinoline-4-carboxamide	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0007	uM
N-[2-[(2S)-2-[2-(benzylamino)-2-oxoacetyl]pyrrolidin-1-yl]-2-oxoethyl]quinoline-4-carboxamide	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0008	uM
2-[4-(carboxymethyl)-6-[carboxymethyl(methyl)amino]-6-[4-[2-[[2-[4-[4-[[2-[(2S)-2-cyano-4,4-difluoropyrrolidin-1-yl]-2-oxoethyl]carbamoyl]quinolin-6-yl]oxybutylamino]-3,4-dioxocyclobuten-1-yl]amino]ethylamino]butyl]-1,4-diazepan-1-yl]acetic acid	2106067: Inhibition of FAP (unknown origin)	ic50	0.0008	uM
N-[2-[(2S)-2-cyano-4,4-difluoropyrrolidin-1-yl]-2-oxoethyl]-2-[(2,4-dichlorophenyl)methyl]-1,3-thiazole-4-carboxamide	1709022: Inhibition of FAP (unknown origin) using AMC substrate by fluorometric assay	ic50	0.0010	uM
methyl 2-[[2-oxo-2-[(2S)-1-[2-(quinoline-4-carbonylamino)acetyl]pyrrolidin-2-yl]acetyl]amino]acetate	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0011	uM
methyl 2-[[2-oxo-2-[(2S)-1-[2-(quinoline-4-carbonylamino)acetyl]pyrrolidin-2-yl]acetyl]amino]propanoate	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0011	uM
N-[2-oxo-2-[(2S)-2-[2-oxo-2-[[2-oxo-2-(propan-2-ylamino)ethyl]amino]acetyl]pyrrolidin-1-yl]ethyl]quinoline-4-carboxamide	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0011	uM
[(2R)-1-[2-(pyridine-3-carbonylamino)acetyl]pyrrolidin-2-yl]boronic acid	736685: Inhibition of human FAP using Z-Gly-Pro-AMC as substrate preincubated for 10 mins prior to substrate addition by fluorescence assay	ic50	0.0011	uM
(2S)-1-[(2S,4S)-4-[2-(1,3-dihydroisoindol-2-yl)-2-oxoethyl]-5-oxopyrrolidine-2-carbonyl]-4,4-difluoropyrrolidine-2-carbonitrile	509577: Competitive inhibition of human recombinant FAP expressed in Hi5 insect cells by Lineweaver-Burke plot analysis	ki	0.0013	uM
N-[2-[(2S)-2-cyano-4,4-difluoropyrrolidin-1-yl]-2-oxoethyl]-6-(3-fluoro-2-methoxypropoxy)quinoline-4-carboxamide	2106032: Inhibition of FAP (unknown origin) using Z-Gly-Pro-7-amino-4-methylcoumarine as fluorogenic substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins	ic50	0.0014	uM
N-[2-[(2S)-2-[2-(4-methoxyanilino)-2-oxoacetyl]pyrrolidin-1-yl]-2-oxoethyl]quinoline-4-carboxamide	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0015	uM
N-[2-[(2S)-2-[2-[[2-[(3,4-dimethoxyphenyl)methylamino]-2-oxoethyl]amino]-2-oxoacetyl]pyrrolidin-1-yl]-2-oxoethyl]quinoline-4-carboxamide	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0017	uM
N-[2-oxo-2-[(2S)-2-[2-oxo-2-[(2-oxo-2-pyrrolidin-1-ylethyl)amino]acetyl]pyrrolidin-1-yl]ethyl]quinoline-4-carboxamide	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0018	uM
N-[2-[(2S)-2-cyano-4,4-difluoropyrrolidin-1-yl]-2-oxoethyl]-6-[(2S,3R)-4-fluoro-2,3-dihydroxybutoxy]quinoline-4-carboxamide	2106032: Inhibition of FAP (unknown origin) using Z-Gly-Pro-7-amino-4-methylcoumarine as fluorogenic substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins	ic50	0.0018	uM
N-[2-[(2S)-2-cyano-4,4-difluoropyrrolidin-1-yl]-2-oxoethyl]-2-[(3,4-dichlorophenyl)methyl]-1,3-thiazole-4-carboxamide	1709022: Inhibition of FAP (unknown origin) using AMC substrate by fluorometric assay	ic50	0.0020	uM
(4S)-5-methoxy-5-oxo-4-[[2-[[2-oxo-2-[(2S)-1-[2-(quinoline-4-carbonylamino)acetyl]pyrrolidin-2-yl]acetyl]amino]acetyl]amino]pentanoic acid	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0021	uM
[(2R)-1-[2-(naphthalene-1-carbonylamino)acetyl]pyrrolidin-2-yl]boronic acid	736685: Inhibition of human FAP using Z-Gly-Pro-AMC as substrate preincubated for 10 mins prior to substrate addition by fluorescence assay	ic50	0.0023	uM
N-[2-[(2S)-2-[2-[[2-(cyclopropylamino)-2-oxoethyl]amino]-2-oxoacetyl]pyrrolidin-1-yl]-2-oxoethyl]quinoline-4-carboxamide	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0027	uM
N-[2-[(2S)-2-[2-(benzhydrylamino)-2-oxoacetyl]pyrrolidin-1-yl]-2-oxoethyl]quinoline-4-carboxamide	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0034	uM
[(2R)-1-[(2R)-2-[(3-chloropyridine-4-carbonyl)amino]propanoyl]pyrrolidin-2-yl]boronic acid	736685: Inhibition of human FAP using Z-Gly-Pro-AMC as substrate preincubated for 10 mins prior to substrate addition by fluorescence assay	ic50	0.0034	uM
4-O-benzyl 1-O-methyl (2S)-2-[[2-[[2-oxo-2-[(2S)-1-[2-(quinoline-4-carbonylamino)acetyl]pyrrolidin-2-yl]acetyl]amino]acetyl]amino]butanedioate	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0037	uM
N-[2-[(2S)-2-[2-[[2-(benzylamino)-2-oxoethyl]amino]-2-oxoacetyl]pyrrolidin-1-yl]-2-oxoethyl]quinoline-4-carboxamide	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0037	uM
N-[2-[(2S)-2-cyano-4,4-difluoropyrrolidin-1-yl]-2-oxoethyl]-2-[(2-naphthalen-2-ylphenyl)methyl]-1,3-thiazole-4-carboxamide	1709022: Inhibition of FAP (unknown origin) using AMC substrate by fluorometric assay	ic50	0.0040	uM
N-[2-oxo-2-[(2S)-2-[2-oxo-2-(propan-2-ylamino)acetyl]pyrrolidin-1-yl]ethyl]quinoline-4-carboxamide	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0040	uM
methyl (2S)-5-amino-5-oxo-2-[[2-[[2-oxo-2-[(2S)-1-[2-(quinoline-4-carbonylamino)acetyl]pyrrolidin-2-yl]acetyl]amino]acetyl]amino]pentanoate	1783814: Inhibition of SF-tagged FAP (unknown origin) expressed in Drosophila S2 cells using fluorogenic substrate by spectrometric analysis	ic50	0.0043	uM
N-[2-[(2S)-2-cyano-4,4-difluoropyrrolidin-1-yl]-2-oxoethyl]-6-(3-fluoro-2-hydroxypropoxy)quinoline-4-carboxamide	2106032: Inhibition of FAP (unknown origin) using Z-Gly-Pro-7-amino-4-methylcoumarine as fluorogenic substrate preincubated for 15 mins followed by substrate addition and measured after 15 mins	ic50	0.0044	uM
[(2S)-1-[2-(1-adamantylamino)acetyl]pyrrolidin-2-yl]boronic acid	255030: Inhibitory activity against human FAP using Lys-Pro-AMC in fluorometric assay	ic50	0.0046	uM

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, increases expression, decreases expression	3
sodium arsenite	decreases expression, increases expression	2
bisphenol S	increases expression, affects cotreatment	2
Air Pollutants	increases abundance, decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
bisphenol F	increases expression	1
potassium chromate(VI)	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
Roflumilast	decreases reaction, increases expression	1
bisphenol B	increases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Ursolic Acid	decreases expression	1
Benzo(a)pyrene	increases methylation, decreases methylation	1
Calcitriol	decreases expression	1
Cisplatin	decreases response to substance, increases expression	1
Dexamethasone	affects cotreatment, decreases expression, increases expression	1
Estradiol	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, decreases expression, increases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Rotenone	increases expression	1
Silicon Dioxide	increases expression	1
Tamoxifen	affects expression	1
Valproic Acid	decreases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression, increases expression	1
Serine Proteinase Inhibitors	decreases reaction, increases cleavage, decreases activity	1

ChEMBL screening assays

130 unique, capped per target: 92 binding, 37 admet, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1003614	Binding	Binding affinity to human FAP assessed as enzyme mediated drug cleavage by measuring Pyro fluorescence	Photodynamic molecular beacon triggered by fibroblast activation protein on cancer-associated fibroblasts for diagnosis and treatment of epithelial cancers. — J Med Chem
CHEMBL3091135	ADMET	Stability of the compound assessed as recombinant human FAPalpha-mediated compound degradation measuring intact level at 0.1 mM after 48 hrs by reverse-phase HPLC/MS analysis	A general method for making peptide therapeutics resistant to serine protease degradation: application to dipeptidyl peptidase IV substrates. — J Med Chem
CHEMBL5723527	Functional	Affinity On-target Cellular interaction: (Competitive radioligand binding assay with unlabelled inhibitor, HT-1080-FAP cells) EUB0002573a FAP	Affinity On-target Cellular Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

7 cell lines: 5 cancer cell line, 1 transformed cell line, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8FS	Abcam HCT 116 FAP KO	Cancer cell line	Male
CVCL_B9HZ	Abcam A-549 FAP KO	Cancer cell line	Male
CVCL_D2F4	Abcam MCF-7 FAP KO	Cancer cell line	Female
CVCL_E1EF	Ubigene U-87 MG FAP KO	Cancer cell line	Male
CVCL_E6AD	HEK293-FAP	Transformed cell line	Female
CVCL_E6QC	Genomeditech CHO-K1 H_FAP	Spontaneously immortalized cell line	Female
CVCL_E8JG	HT1080 human FAP	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.