ALPG

Summary

ALPG (alkaline phosphatase, germ cell, HGNC:441) is a protein-coding gene on chromosome 2q37.1, encoding Alkaline phosphatase, germ cell type (P10696). Alkaline phosphatase that can hydrolyze various phosphate compounds.

There are at least four distinct but related alkaline phosphatases: intestinal, placental, placental-like, and liver/bone/kidney (tissue non-specific). The product of this gene is a membrane bound glycosylated enzyme, localized to testis, thymus and certain germ cell tumors, that is closely related to both the placental and intestinal forms of alkaline phosphatase.

Source: NCBI Gene 251 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 138 total — 3 pathogenic, 1 likely-pathogenic
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_031313

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:441
Approved symbol	ALPG
Name	alkaline phosphatase, germ cell
Location	2q37.1
Locus type	gene with protein product
Status	Approved
Aliases	GCAP
Ensembl gene	ENSG00000163286
Ensembl biotype	protein_coding
OMIM	171810
Entrez	251

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000295453

RefSeq mRNA: 1 — MANE Select: NM_031313 NM_031313

CCDS: CCDS2491

Canonical transcript exons

ENST00000295453 — 11 exons

Exon	Start	End
ENSE00001073014	232407845	232408017
ENSE00001073029	232406844	232406961
ENSE00001145357	232409574	232410714
ENSE00002440603	232408267	232408401
ENSE00002446124	232408921	232409112
ENSE00002450233	232407057	232407173
ENSE00002453649	232407286	232407401
ENSE00002469057	232408501	232408573
ENSE00002518742	232409332	232409448
ENSE00002520059	232407594	232407768
ENSE00002527695	232408704	232408838

Expression profiles

Bgee: expression breadth broad, 29 present calls, max score 85.93.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.3179 / max 3163.9009, expressed in 109 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
25966	2.3179	109

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
triceps brachii	UBERON:0001509	85.93	gold quality
gluteal muscle	UBERON:0002000	84.37	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	79.84	gold quality
inferior olivary complex	UBERON:0002127	78.63	gold quality
vena cava	UBERON:0004087	78.08	gold quality
vastus lateralis	UBERON:0001379	77.97	gold quality
diaphragm	UBERON:0001103	76.52	gold quality
quadriceps femoris	UBERON:0001377	76.42	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.15	gold quality
biceps brachii	UBERON:0001507	75.84	gold quality
cervix squamous epithelium	UBERON:0006922	75.51	gold quality
heart right ventricle	UBERON:0002080	74.96	gold quality
cerebellar vermis	UBERON:0004720	74.84	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	73.40	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	72.21	gold quality
myocardium	UBERON:0002349	71.45	gold quality
oocyte	CL:0000023	70.66	gold quality
pons	UBERON:0000988	70.44	silver quality
cardia of stomach	UBERON:0001162	70.27	gold quality
body of tongue	UBERON:0011876	70.07	gold quality
parotid gland	UBERON:0001831	70.02	gold quality
secondary oocyte	CL:0000655	69.82	gold quality
medulla oblongata	UBERON:0001896	69.81	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	69.52	gold quality
thymus	UBERON:0002370	69.49	silver quality
paraflocculus	UBERON:0005351	69.29	gold quality
frontal pole	UBERON:0002795	68.94	gold quality
tongue	UBERON:0001723	68.87	gold quality
dorsal plus ventral thalamus	UBERON:0001897	68.68	gold quality
middle frontal gyrus	UBERON:0002702	68.49	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-10018	yes	1266.79
E-ANND-3	no	0.49

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR

miRNA regulators (miRDB)

31 targeting ALPG, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-502-5P	98.77	66.51	906
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-296-5P	97.61	64.02	851
HSA-MIR-4308	97.56	67.13	1385
HSA-MIR-335-5P	97.10	68.12	1022
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-6762-5P	96.55	64.62	972
HSA-MIR-6845-5P	96.55	64.65	969
HSA-MIR-1343-5P	96.48	66.06	1506
HSA-MIR-3657	96.33	66.29	608

Literature-anchored findings (GeneRIF, showing 8)

• the structural differences in human AP isoforms are demonstrated through models (PMID:12372831)
• These results indicate that IAP is strongly involved in chylomicron formation and fatty acid metabolism might change among ABO blood type. (PMID:16412386)
• Premature induction of hypertrophy-related molecules (type X collagen and matrix metalloproteinase 13) occurred before production of type II collagen and was followed by up-regulation of alkaline phosphatase activity. (PMID:17009260)
• aptamer-mediated identification of ALPPL-2 on the cell surface and cell secretions of pancreatic cancer cells supports its potential use in the serum- and membrane-based diagnosis of PDAC (PMID:23467613)
• Our results indicated that the expression of ALPPL2 was significantly increased in gastric adenocarcinoma and was an independent factor that could provide reliable prognostic information on gastric adenocarcinoma patients (PMID:30496798)
• GWAS identified a novel gene encoding an anastrozole transporter, SLC38A7, as well as epistatic interaction between SNPs in that gene and SNPs near ALPPL2 that influenced both the expression of the transporter and anastrozole plasma concentrations (PMID:30648747)
• Identification of ALPPL2 as a Naive Pluripotent State-Specific Surface Protein Essential for Human Naive Pluripotency Regulation. (PMID:32187559)
• ALPPL2 Is a Highly Specific and Targetable Tumor Cell Surface Antigen. (PMID:32868383)

Cross-species orthologs

21 orthologs

Organism	Symbol	Gene ID
danio_rerio	alpi.2	ENSDARG00000053774
mus_musculus	Alppl2	ENSMUSG00000026246
mus_musculus	Akp3	ENSMUSG00000036500
mus_musculus	Alpi	ENSMUSG00000079440
rattus_norvegicus	Alpi	ENSRNOG00000030020
rattus_norvegicus	Alpp	ENSRNOG00000033672
rattus_norvegicus	Alpg	ENSRNOG00000042889
rattus_norvegicus	Akp3	ENSRNOG00000058652
drosophila_melanogaster	Alp4	FBGN0016123
drosophila_melanogaster	Alp11	FBGN0030661
drosophila_melanogaster	Alp12	FBGN0032779
drosophila_melanogaster	Alp6	FBGN0033423
drosophila_melanogaster	Alp7	FBGN0034710
drosophila_melanogaster	Alp8	FBGN0034712
drosophila_melanogaster	Alp10	FBGN0035619
drosophila_melanogaster	Alp9	FBGN0035620
drosophila_melanogaster	Alp13	FBGN0037786
drosophila_melanogaster	Alp5	FBGN0038845
drosophila_melanogaster	phu	FBGN0043791
drosophila_melanogaster	Alp1	FBGN0283479
drosophila_melanogaster	Alp2	FBGN0283480

Paralogs (3): ALPL (ENSG00000162551), ALPP (ENSG00000163283), ALPI (ENSG00000163295)

Protein

Protein identifiers

Alkaline phosphatase, germ cell type — P10696 (reviewed: P10696)

Alternative names: ALP-1, Alkaline phosphatase Nagao isozyme, Alkaline phosphatase, placental-like, Germ cell alkaline phosphatase, Placental alkaline phosphatase-like

All UniProt accessions (1): P10696

UniProt curated annotations — full annotation on UniProt →

Function. Alkaline phosphatase that can hydrolyze various phosphate compounds.

Subunit / interactions. Homodimer.

Subcellular location. Cell membrane.

Tissue specificity. Trace amounts in the testis and thymus, and in elevated amounts in germ cell tumors.

Activity regulation. Inhibited by L-leucine, EDTA and heat.

Cofactor. Binds 1 Mg(2+) ion. Binds 2 Zn(2+) ions.

Miscellaneous. In most mammals there are four different isozymes: placental (ALPP), germ cell (ALPG), intestinal (ALPI) and tissue non-specific (liver/bone/kidney) (ALPL/TNAP).

Similarity. Belongs to the alkaline phosphatase family.

RefSeq proteins (1): NP_112603* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001952	Alkaline_phosphatase	Family
IPR017850	Alkaline_phosphatase_core_sf	Homologous_superfamily
IPR018299	Alkaline_phosphatase_AS	Active_site

Pfam: PF00245

Catalyzed reactions (Rhea), 1 shown:

• a phosphate monoester + H2O = an alcohol + phosphate (RHEA:15017)

UniProt features (36 total): binding site 14, sequence conflict 8, sequence variant 3, glycosylation site 2, disulfide bond 2, signal peptide 1, chain 1, propeptide 1, lipid moiety-binding region 1, region of interest 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10696-F1	93.31	0.90

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 (1): 111 (phosphoserine intermediate)

Ligand- & substrate-binding residues (14): 235; 288; 289; 304; 330; 335; 339; 376; 377; 451; 61; 61 …

Post-translational modifications (1): 503

Disulfide bonds (2): 140–202, 486–493

Glycosylation sites (2): 141, 268

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-163125	Post-translational modification: synthesis of GPI-anchored proteins

MSigDB gene sets: 71 (showing top): MODULE_571, TGACCTY_ERR1_Q2, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, MORF_PDPK1, WONG_ENDMETRIUM_CANCER_UP, GOCC_SIDE_OF_MEMBRANE, MODULE_55, ER_Q6_02, MODULE_13, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_PHOSPHORIC_ESTER_HYDROLASE_ACTIVITY, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, KEGG_FOLATE_BIOSYNTHESIS, MODULE_41, GOMF_PHOSPHATASE_ACTIVITY

GO Biological Process (0):

GO Molecular Function (4): alkaline phosphatase activity (GO:0004035), metal ion binding (GO:0046872), hydrolase activity (GO:0016787), phosphatase activity (GO:0016791)

GO Cellular Component (4): extracellular region (GO:0005576), plasma membrane (GO:0005886), side of membrane (GO:0098552), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Post-translational protein modification	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
membrane	2
phosphatase activity	1
cation binding	1
catalytic activity	1
phosphoric ester hydrolase activity	1
cell periphery	1
leaflet of membrane bilayer	1

Protein interactions and networks

STRING

1102 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ALPG	GGT6	Q6P531	772
ALPG	GGT7	Q9UJ14	767
ALPG	GOT1L1	Q8NHS2	740
ALPG	GGT2P	P36268	723
ALPG	GGT5	P36269	698
ALPG	GOT1	P17174	673
ALPG	GGT1	P19440	633
ALPG	LDHAL6B	Q9BYZ2	627
ALPG	LDHAL6A	Q6ZMR3	618
ALPG	F2RL3	Q96RI0	591
ALPG	LDHC	P07864	575
ALPG	ZC3H11B	A0A1B0GTU1	571
ALPG	GOT2	P00505	546
ALPG	NPEPPS	P55786	521
ALPG	INO80	Q9ULG1	512

IntAct

10 interactions, top by confidence:

A	B	Type	Score
ALPG	ALPP	psi-mi:“MI:0914”(association)	0.530
Erh	BCLAF3	psi-mi:“MI:0915”(physical association)	0.400
Cep76	DCTN2	psi-mi:“MI:0915”(physical association)	0.400
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
TEX101	PSMD12	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
ALPG	POTEF	psi-mi:“MI:0914”(association)	0.350
ALPP	MAN2B1	psi-mi:“MI:0914”(association)	0.350

BioGRID (45): ALPP (Affinity Capture-MS), USP16 (Affinity Capture-MS), ALPI (Affinity Capture-MS), PCOLCE2 (Affinity Capture-MS), B3GALTL (Affinity Capture-MS), GALNS (Affinity Capture-MS), AHNAK (Affinity Capture-MS), ALPPL2 (Affinity Capture-MS), ALPPL2 (Affinity Capture-MS), ALPPL2 (Affinity Capture-MS), ALPPL2 (Affinity Capture-MS), ALPPL2 (Affinity Capture-MS), ALPPL2 (Affinity Capture-MS), ALPPL2 (Affinity Capture-MS), ALPI (Affinity Capture-MS)

ESM2 similar proteins: F1NZI4, O00754, O09008, O35082, O35795, O46432, O55026, O89023, O97583, P04062, P10696, P11117, P16301, P17405, P17439, P18424, P20611, P21139, P24638, P24823, P52849, P52850, P53761, P58242, Q04519, Q0P5F0, Q0V8B6, Q0VD19, Q2KHZ8, Q4R5N9, Q5NVF6, Q5R8E3, Q5RFU0, Q6XPZ3, Q6YGZ1, Q6ZNF0, Q70KH2, Q71RP1, Q8BP56, Q8BX37

Diamond homologs: O60109, P00634, P05186, P05187, P08289, P09242, P09487, P09923, P10696, P11491, P15693, P19111, P21948, P24822, P24823, P29523, P51740, P83456, Q24238, Q29486, Q92058, P19405, P19147, P35483, Q02QC9, P09401, P19406

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	105
Likely benign	14
Benign	10

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
144230	GRCh38/hg38 2q37.1(chr2:231892041-232652305)x1	Pathogenic
147843	GRCh38/hg38 2q36.3-37.2(chr2:228014149-234976424)x3	Pathogenic
1526959	GRCh37/hg19 2q36.3-37.1(chr2:228807574-235475892)	Pathogenic
1526962	GRCh37/hg19 2q37.1(chr2:232215111-235593473)	Likely pathogenic

SpliceAI

909 predictions. Top by Δscore:

Variant	Effect	Δscore
2:232406957:CCCAG:C	donor_loss	1.0000
2:232406958:CCAG:C	donor_loss	1.0000
2:232406959:CAGG:C	donor_loss	1.0000
2:232406960:AGG:A	donor_loss	1.0000
2:232406961:GGT:G	donor_loss	1.0000
2:232406962:G:C	donor_loss	1.0000
2:232406963:T:G	donor_loss	1.0000
2:232407050:T:A	acceptor_gain	1.0000
2:232407051:G:A	acceptor_gain	1.0000
2:232407052:GCCA:G	acceptor_loss	1.0000
2:232407053:CCA:C	acceptor_loss	1.0000
2:232407054:CAGTT:C	acceptor_loss	1.0000
2:232407055:A:AC	acceptor_loss	1.0000
2:232407055:A:AG	acceptor_gain	1.0000
2:232407055:AGTT:A	acceptor_gain	1.0000
2:232407056:G:GA	acceptor_gain	1.0000
2:232407056:GT:G	acceptor_gain	1.0000
2:232407056:GTT:G	acceptor_gain	1.0000
2:232407056:GTTG:G	acceptor_gain	1.0000
2:232407056:GTTGA:G	acceptor_gain	1.0000
2:232407170:GACG:G	donor_gain	1.0000
2:232407174:G:GG	donor_gain	1.0000
2:232407174:GT:G	donor_loss	1.0000
2:232407175:T:G	donor_loss	1.0000
2:232407176:GAGT:G	donor_loss	1.0000
2:232407178:G:GG	donor_gain	1.0000
2:232407283:CAGG:C	acceptor_loss	1.0000
2:232407284:A:AG	acceptor_gain	1.0000
2:232407284:AGG:A	acceptor_gain	1.0000
2:232407285:G:GG	acceptor_gain	1.0000

AlphaMissense

3442 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:232407624:A:C	S111R	0.992
2:232407626:T:A	S111R	0.992
2:232407626:T:G	S111R	0.992
2:232407171:A:T	D61V	0.991
2:232407662:G:C	K123N	0.991
2:232407662:G:T	K123N	0.991
2:232409636:G:C	D455H	0.991
2:232409056:A:T	D376V	0.990
2:232407173:G:T	G62W	0.989
2:232408820:T:C	F325L	0.989
2:232408822:C:A	F325L	0.989
2:232408822:C:G	F325L	0.989
2:232408933:A:T	D335V	0.989
2:232407979:G:C	D204H	0.988
2:232408286:G:C	R223P	0.988
2:232408934:C:A	D335E	0.987
2:232408934:C:G	D335E	0.987
2:232407316:G:T	R72M	0.986
2:232407654:G:T	G121W	0.986
2:232409059:A:C	H377P	0.986
2:232409055:G:C	D376H	0.985
2:232407995:T:C	L209P	0.984
2:232408836:A:T	E330V	0.984
2:232409053:C:A	A375D	0.984
2:232407286:G:T	G62V	0.983
2:232409057:C:A	D376E	0.983
2:232409057:C:G	D376E	0.983
2:232407170:G:C	D61H	0.982
2:232407171:A:C	D61A	0.982
2:232407863:T:A	V165E	0.982

dbSNP variants (sampled 300 via entrez): RS1001565605 (2:232409079 G>A,C,T), RS1002575086 (2:232410421 C>G), RS1002723586 (2:232405481 G>A), RS1003794478 (2:232406650 G>T), RS1003854496 (2:232411109 T>C,G), RS1003889152 (2:232405850 G>A), RS1004125813 (2:232406500 C>T), RS1004451848 (2:232410766 G>T), RS1005851484 (2:232407557 T>C,G), RS1006383711 (2:232407717 A>G), RS1006833477 (2:232407287 G>A), RS1007465401 (2:232406101 C>T), RS1008764432 (2:232405113 T>C), RS1009934 (2:232410170 C>G), RS1010185687 (2:232405464 A>G)

Disease associations

OMIM: gene MIM:171810 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006585_1075	Blood protein levels	1.000000e-13
GCST006585_1717	Blood protein levels	2.000000e-10
GCST010002_411	Refractive error	1.000000e-123
GCST012226_602	Waist circumference adjusted for body mass index	1.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3402 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 118,080 (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
CHEMBL140	CURCUMIN	3	93,882
CHEMBL442687	TIOXOLONE	2	4,031
CHEMBL583912	(-)-EPICATECHIN	2	20,167

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

Binding affinities (BindingDB)

533 measured of 824 human assays (866 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[2-[(3’R,3’aS,4aR,6’S,6aR,6bS,7’aR,9S,12aS,12bS)-3’,6’,11,12b-tetramethyl-3-oxospiro[2,4,4a,5,6,6a,6b,7,8,10,12,12a-dodecahydro-1H-naphtho[2,1-a]azulene-9,2’-3,3a,5,6,7,7a-hexahydrofuro[3,2-b]pyridine]-4’-yl]ethyl]acetamide	EC50	60 nM	US-10314827: Methods of use of cyclopamine analogs
benzyl (3R,3’R,3’aS,4aR,6’S,6aR,6bS,7’aR,9S,12aS,12bS)-3-hydroxy-3’,6’,11,12b-tetramethylspiro[1,2,3,4,4a,5,6,6a,6b,7,8,10,12,12a-tetradecahydronaphtho[2,1-a]azulene-9,2’-3,3a,5,6,7,7a-hexahydrofuro[3,2-b]pyridine]-4’-carboxylate	EC50	60 nM	US-10314827: Methods of use of cyclopamine analogs
benzyl (3S,3’R,3’aS,4aR,6’S,6aR,6bS,7’aR,9S,12aS,12bS)-3-hydroxy-3’,6’,11,12b-tetramethylspiro[1,2,3,4,4a,5,6,6a,6b,7,8,10,12,12a-tetradecahydronaphtho[2,1-a]azulene-9,2’-3,3a,5,6,7,7a-hexahydrofuro[3,2-b]pyridine]-4’-carboxylate	EC50	60 nM	US-10314827: Methods of use of cyclopamine analogs
(3R,3’R,3’aS,4aR,6’S,6aR,6bS,7’aR,9S,12aS,12bS)-3-methoxy-3’,6’,11,12b-tetramethylspiro[1,2,3,4,4a,5,6,6a,6b,7,8,10,12,12a-tetradecahydronaphtho[2,1-a]azulene-9,2’-3a,4,5,6,7,7a-hexahydro-3H-furo[3,2-b]pyridine]	EC50	60 nM	US-10314827: Methods of use of cyclopamine analogs
benzyl (3R,3’R,3’aS,4aR,6’S,6aR,6bS,7’aR,9S,12aS,12bS)-3-[2-(benzylamino)acetyl]oxy-3’,6’,11,12b-tetramethylspiro[1,2,3,4,4a,5,6,6a,6b,7,8,10,12,12a-tetradecahydronaphtho[2,1-a]azulene-9,2’-3,3a,5,6,7,7a-hexahydrofuro[3,2-b]pyridine]-4’-carboxylate	EC50	60 nM	US-10314827: Methods of use of cyclopamine analogs
2-(5-Phenyl-2H-[1,2,4]triazol-3-yl)-3a,4,7,7a-tetrahydro-isoindole-1,3-dione	IC50	110 nM
4-chloranyl-N-(3,4-dihydro-2H-thiochromen-4-yl)-3-sulfamoyl-benzamide	IC50	121 nM
(3E)-3-[[2-(3,4-dihydroxyphenyl)ethylamino]methylene]oxindole	IC50	374 nM
3-[2-(3,4-dihydroxyphenyl)ethyl]-8-fluoro-5H-pyrimid[5,4-b]indol-4-one	IC50	1040 nM
2-[2-oxidanylidene-2-[2-[(Z)-(3-oxidanyl-4-oxidanylidene-cyclohexa-2,5-dien-1-ylidene)methyl]hydrazinyl]ethoxy]-N’’-[(Z)-(3-oxidanyl-4-oxidanylidene-cyclohexa-2,5-dien-1-ylidene)methyl]benzohydrazide	IC50	1070 nM
1-(3,4-dihydroxyphenyl)-2-(1-(4-methoxyphenyl)-1H-tetrazol-5-ylthio)ethanone	IC50	1130 nM
1-(3,4-dihydroxyphenyl)-2-(4,6-dimethylpyrimidin-2-ylthio)ethanone	IC50	1210 nM
2-[5-[(Z)-(3-bromanyl-8-oxidanylidene-[1,3]thiazolo[4,5]imidazo[1,2-b]pyridin-7-ylidene)methyl]furan-2-yl]benzoic acid	IC50	1250 nM
1-(3,4-dihydroxyphenyl)-2-[(5-ethyl-1H-1,2,4-triazol-3-yl)sulfanyl]ethanone	IC50	1270 nM
Cephalochromin	IC50	1490 nM
2-[[5-(1,3-benzothiazol-2-ylsulfanylmethyl)-4-ethyl-1,2,4-triazol-3-yl]sulfanyl]-1-(3,4-dihydroxyphenyl)ethanone	IC50	1520 nM
(5Z)-3-[[(E)-(6-keto-3-nitro-cyclohexa-2,4-dien-1-ylidene)methyl]amino]-5-[(5-methyl-2-furyl)methylene]-2-thioxo-thiazolidin-4-one	IC50	1530 nM
(2Z)-2-(3,4-dihydroxybenzylidene)-6-hydroxy-coumaran-3-one	IC50	1530 nM
1-(3,4-dihydroxyphenyl)-2-[[5-(2-methoxyphenyl)-4-prop-2-enyl-1,2,4-triazol-3-yl]sulfanyl]ethanone	IC50	1550 nM
2-[2-(3,4-dihydroxyphenyl)-2-oxoethyl]sulfanyl-4,6-dimethylpyridine-3-carbonitrile	IC50	1560 nM
1-(3,4-dihydroxyphenyl)-2-[1-(4-methylphenyl)tetrazol-5-yl]sulfanylethanone	IC50	1580 nM
3-[6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-5-phenyl-pentanoic acid	IC50	1610 nM
(5Z)-5-[(E)-3-(2-furanyl)prop-2-enylidene]-3-(4-hydroxyphenyl)-2-sulfanylidene-4-thiazolidinone	IC50	1720 nM
4-[5-[2-(3,4-dihydroxyphenyl)-2-oxoethyl]sulfanyltetrazol-1-yl]benzamide	IC50	1760 nM
3-(2-(3,4-dihydroxyphenyl)-2-oxoethyl)-6,7-dimethoxyisobenzofuran-1(3H)-one	IC50	1830 nM
4-[5-[(Z)-[3-(1,1-diketothiolan-3-yl)-4-keto-2-thioxo-thiazolidin-5-ylidene]methyl]-2-furyl]benzenesulfonamide	IC50	1850 nM
SMR000039131	IC50	1880 nM
1-(3,4-dihydroxyphenyl)-2-[1-(4-fluorophenyl)tetrazol-5-yl]sulfanylethanone	IC50	1890 nM
MLS000102658	EC50	1910 nM
4-(2-benzylsulfanylethyl)pyridine;phosphoric acid	IC50	2010 nM
2-(3-benzyl-1H-1,2,4-triazol-5-yl)-3a,4,7,7a-tetrahydro-1H-isoindole-1,3(2H)-dione	IC50	2040 nM
2-[5-(2-furanyl)-1H-1,2,4-triazol-3-yl]-1,3-dioxo-5-isoindolecarboxylic acid	IC50	2060 nM
MLS001224314	IC50	2080 nM
1-(3,4-dihydroxyphenyl)-2-(4-methyl-1H-pyrazol-1-yl)ethanone	IC50	2130 nM
2-(2-(3,4-dihydroxyphenyl)-2-oxoethylthio)-4-(methoxymethyl)-6-methylnicotinonitrile	IC50	2160 nM
SMR000369921	IC50	2350 nM
1-(3,4-dihydroxyphenyl)-2-(2-methyl-1-imidazolyl)ethanone;hydrochloride	IC50	2370 nM
MLS000778637	IC50	2420 nM
1-(3,4-dihydroxyphenyl)-2-(2-methyl-1-benzimidazolyl)ethanone;hydrochloride	IC50	2510 nM
(1S)-1,5-anhydro-1-(1,3,6,7-tetrahydroxy-9-oxo-9H-xanthen-2-yl)-D-glucitol	IC50	2710 nM
5,6-Dimethyl-2-[1-(1-thiophen-2-ylmethyl-1H-tetrazol-5-ylmethyl)-piperidin-4-yl]-1H-benzoimidazole	IC50	2730 nM
MLS000720395	IC50	2820 nM
3-[5-(methylamino)-1,3,4-thiadiazol-2-yl]-1-benzopyran-2-one	IC50	2850 nM
2-(2,4-dichlorostyryl)-1H-1,3-benzimidazole	IC50	2850 nM
1-(3,4-dihydroxyphenyl)-2-[(4-prop-2-enyl-5-pyridin-3-yl-1,2,4-triazol-3-yl)sulfanyl]ethanone	IC50	2920 nM
2-(3,4-dihydroxyphenyl)-7,8-dihydroxy-2,3-dihydrochromen-4-one	IC50	2990 nM
2-amino-3-hydroxy-N’-(2,3,4-trihydroxybenzyl)propionohydrazide;hydrochloride	IC50	3050 nM
2-(Benzooxazol-2-ylsulfanyl)-1-(3,4-dihydroxy-phenyl)-ethanone	IC50	3060 nM
MLS000778639	IC50	3100 nM
5-amino-6-[(Z)-(3-hydroxy-4-keto-cyclohexa-2,5-dien-1-ylidene)methyl]-3-phenyl-thiazolo[3,2-a]pyrimidin-7-one	IC50	3100 nM

ChEMBL bioactivities

136 potent at pChembl≥5 of 464 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.22	EC50	60	nM	CHEMBL5820397
7.22	EC50	60	nM	CHEMBL6055533
7.22	EC50	60	nM	CHEMBL5893768
7.22	EC50	60	nM	CHEMBL559431
7.22	EC50	60	nM	CHEMBL5874649
6.69	EC50	203	nM	CHEMBL1302272
6.43	IC50	374	nM	CHEMBL1734721
6.34	EC50	457	nM	CHEMBL1336276
6.26	EC50	550	nM	CHEMBL1300370
6.22	IC50	600	nM	CHEMBL592869
6.18	EC50	663	nM	CHEMBL6195777
6.14	EC50	718	nM	CHEMBL1505198
5.98	IC50	1040	nM	CHEMBL1732263
5.96	EC50	1090	nM	CHEMBL1302946
5.95	IC50	1130	nM	CHEMBL254255
5.92	IC50	1200	nM	CHEMBL349641
5.92	IC50	1210	nM	CHEMBL592869
5.85	IC50	1420	nM	CHEMBL254255
5.82	IC50	1520	nM	CHEMBL1526624
5.82	IC50	1530	nM	CHEMBL1715095
5.81	IC50	1550	nM	CHEMBL1323944
5.81	IC50	1560	nM	CHEMBL1705147
5.80	IC50	1580	nM	CHEMBL1706513
5.77	IC50	1700	nM	CHEMBL607856
5.75	IC50	1760	nM	CHEMBL1439735
5.74	IC50	1830	nM	CHEMBL610508
5.73	IC50	1880	nM	CHEMBL1302459
5.72	EC50	1910	nM	CHEMBL1375639
5.72	IC50	1890	nM	CHEMBL1375393
5.70	IC50	2010	nM	CHEMBL1499077
5.69	IC50	2040	nM	CHEMBL1372823
5.68	IC50	2110	nM	CHEMBL1312616
5.68	IC50	2110	nM	CHEMBL1715345
5.67	IC50	2130	nM	CHEMBL610781
5.67	IC50	2160	nM	CHEMBL598663
5.63	IC50	2350	nM	CHEMBL3194421
5.62	IC50	2370	nM	CHEMBL1699194
5.60	IC50	2530	nM	CHEMBL1727550
5.60	IC50	2510	nM	CHEMBL1412999
5.60	IC50	2490	nM	CHEMBL592869
5.58	EC50	2650	nM	CHEMBL1572262
5.58	IC50	2600	nM	CHEMBL1323944
5.57	IC50	2700	nM	CHEMBL608723
5.57	IC50	2710	nM	CHEMBL1329826
5.56	IC50	2730	nM	CHEMBL1489864
5.55	IC50	2790	nM	CHEMBL1323944
5.54	IC50	2850	nM	CHEMBL1529932
5.54	IC50	2850	nM	CHEMBL1371339
5.54	IC50	2920	nM	CHEMBL1576140
5.53	IC50	2950	nM	CHEMBL610508

PubChem BioAssay actives

10 with measured affinity, of 56 total; 10 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-(1,3-benzothiazol-2-yl)-6-hydroxy-2-oxo-1H-quinoline-4-carboxamide	1929444: Inhibition of human germ cell alkaline phosphatase	ic50	0.0750	uM
N-(1,3-benzothiazol-2-yl)-7-chloro-6-methoxy-2-oxo-1H-quinoline-4-carboxamide	1929444: Inhibition of human germ cell alkaline phosphatase	ic50	0.0750	uM
N-(1,3-benzothiazol-2-yl)-7-chloro-6-methyl-2-oxo-1H-quinoline-4-carboxamide	1929444: Inhibition of human germ cell alkaline phosphatase	ic50	0.0750	uM
N-(1,3-benzothiazol-2-yl)-6,7-dimethyl-2-oxo-1H-quinoline-4-carboxamide	1929444: Inhibition of human germ cell alkaline phosphatase	ic50	0.0750	uM
1-(3,4-dihydroxyphenyl)-2-(4,6-dimethylpyrimidin-2-yl)sulfanylethanone	459068: Inhibition of GCAP by analogous luminescence assay	ic50	0.6000	uM
1-(3,4-dihydroxyphenyl)-2-imidazol-1-ylethanone	459068: Inhibition of GCAP by analogous luminescence assay	ic50	1.2000	uM
1-(3,4-dihydroxyphenyl)-2-(2-ethylimidazol-1-yl)ethanone	459068: Inhibition of GCAP by analogous luminescence assay	ic50	1.7000	uM
2-(benzimidazol-1-yl)-1-(3,4-dihydroxyphenyl)ethanone	459068: Inhibition of GCAP by analogous luminescence assay	ic50	2.7000	uM
2-(1H-benzimidazol-2-ylamino)-1-(3,4-dihydroxyphenyl)ethanone	459068: Inhibition of GCAP by analogous luminescence assay	ic50	6.2000	uM
1-(3,4-dihydroxyphenyl)-2-(2-methylbenzimidazol-1-yl)ethanone	459068: Inhibition of GCAP by analogous luminescence assay	ic50	9.4000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	4
Genistein	increases expression	4
bisphenol A	decreases expression, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Diethylstilbestrol	increases expression	2
Estradiol	increases activity, increases expression	2
sotorasib	increases expression, affects cotreatment	1
dicrotophos	increases expression	1
daidzein	increases expression	1
4-hydroxyestradiol	increases activity	1
sulforaphane	decreases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
ICG 001	increases expression	1
trametinib	increases expression, affects cotreatment	1
NVP-BKM120	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases expression	1
Diethylnitrosamine	decreases expression	1
Succimer	affects cotreatment, increases expression	1
Ethinyl Estradiol	increases expression	1
Etoposide	affects response to substance	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases methylation	1
Zearalenone	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Lithium Chloride	increases expression	1

ChEMBL screening assays

17 unique, capped per target: 10 binding, 7 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1074491	Binding	Inhibition of GCAP by analogous luminescence assay	Design and synthesis of selective inhibitors of placental alkaline phosphatase. — Bioorg Med Chem
CHEMBL1614344	Functional	PUBCHEM_BIOASSAY: Luminescent assay for HTS discovery of chemical inhibitors of placental alkaline phosphatase. (Class of assay: confirmatory) [Related pubchem assays: 1512, 518 ]	PubChem BioAssay data set

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery