LIPC

Summary

LIPC (lipase C, hepatic type, HGNC:6619) is a protein-coding gene on chromosome 15q21.3, encoding Hepatic triacylglycerol lipase (P11150). Catalyzes the hydrolysis of triglycerides and phospholipids present in circulating plasma lipoproteins, including chylomicrons, intermediate density lipoproteins (IDL), low density lipoproteins (LDL) of large size and high density lipoproteins (HDL), releasing free fatty acids (….

Enables phospholipase A1 activity and triacylglycerol lipase activity. Involved in several processes, including cholesterol homeostasis; plasma lipoprotein particle remodeling; and triglyceride catabolic process. Located in extracellular space. Implicated in several diseases, including Alzheimer’s disease; coronary artery disease; familial combined hyperlipidemia; peripheral vascular disease; and type 2 diabetes mellitus. Biomarker of hyperinsulinism; obesity; and type 1 diabetes mellitus.

Source: NCBI Gene 3990 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hyperlipidemia due to hepatic triglyceride lipase deficiency (Strong, GenCC)
• GWAS associations: 336
• Clinical variants (ClinVar): 355 total — 3 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 13
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000236

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6619
Approved symbol	LIPC
Name	lipase C, hepatic type
Location	15q21.3
Locus type	gene with protein product
Status	Approved
Aliases	HL, HTGL
Ensembl gene	ENSG00000166035
Ensembl biotype	protein_coding
OMIM	151670
Entrez	3990

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 23 protein_coding, 3 retained_intron

ENST00000299022, ENST00000356113, ENST00000414170, ENST00000433326, ENST00000559845, ENST00000560257, ENST00000560664, ENST00000901639, ENST00000901640, ENST00000901641, ENST00000901642, ENST00000901643, ENST00000901644, ENST00000901645, ENST00000901646, ENST00000901647, ENST00000901648, ENST00000901649, ENST00000901650, ENST00000901651, ENST00000901652, ENST00000901653, ENST00000901654, ENST00000901655, ENST00000901656, ENST00000901657

RefSeq mRNA: 1 — MANE Select: NM_000236 NM_000236

CCDS: CCDS10166

Canonical transcript exons

ENST00000299022 — 9 exons

Exon	Start	End
ENSE00001099170	58563505	58563723
ENSE00001141787	58538333	58538517
ENSE00001930067	58568716	58569844
ENSE00003468798	58541785	58541967
ENSE00003471180	58542534	58542651
ENSE00003548373	58560864	58560981
ENSE00003549295	58545742	58545975
ENSE00003583777	58431991	58432120
ENSE00003606177	58548330	58548572

Expression profiles

Bgee: expression breadth ubiquitous, 158 present calls, max score 96.29.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3025 / max 190.4220, expressed in 280 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146937	0.6502	232
146939	0.4430	41
146938	0.1984	42
207540	0.0109	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	96.29	gold quality
liver	UBERON:0002107	95.89	gold quality
colonic epithelium	UBERON:0000397	93.92	gold quality
tibial nerve	UBERON:0001323	77.77	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.95	silver quality
metanephros cortex	UBERON:0010533	75.33	gold quality
monocyte	CL:0000576	74.47	gold quality
mononuclear cell	CL:0000842	74.24	gold quality
sural nerve	UBERON:0015488	73.84	gold quality
leukocyte	CL:0000738	73.64	gold quality
adult mammalian kidney	UBERON:0000082	69.84	gold quality
kidney	UBERON:0002113	67.33	gold quality
cortex of kidney	UBERON:0001225	67.11	gold quality
islet of Langerhans	UBERON:0000006	65.94	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	65.70	gold quality
mucosa of transverse colon	UBERON:0004991	65.58	gold quality
calcaneal tendon	UBERON:0003701	65.47	gold quality
metanephros	UBERON:0000081	64.41	gold quality
granulocyte	CL:0000094	64.10	gold quality
stromal cell of endometrium	CL:0002255	63.60	gold quality
spinal cord	UBERON:0002240	63.12	gold quality
renal glomerulus	UBERON:0000074	62.62	silver quality
right atrium auricular region	UBERON:0006631	62.62	gold quality
cardiac atrium	UBERON:0002081	61.53	gold quality
pancreas	UBERON:0001264	61.36	gold quality
gall bladder	UBERON:0002110	60.99	gold quality
prefrontal cortex	UBERON:0000451	60.84	gold quality
rectum	UBERON:0001052	60.83	gold quality
metanephric glomerulus	UBERON:0004736	60.80	gold quality
bone marrow cell	CL:0002092	60.78	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	608.81
E-ANND-3	no	4.31

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, CNBP, ESR1, HNF1A, HNF4A, NR2F2, PITX2, SREBF1, SREBF2, USF1, USF2

Literature-anchored findings (GeneRIF, showing 40)

• The -514C/T polymorphism of the HL gene was found to be associated with variations in hepatic lipase activity and serum HDL-C levels. (PMID:11947893)
• synthesized in peritoneal macrophages (PMID:11971936)
• The T allele of the hepatic lipase-514 C/T polymorphism is related to changes in plasma lipids. The superficially paradoxical predisposition to CHD in males is attributable to impairment of TG rich lipoprotein metabolism and reverse cholesterol transport. (PMID:12006918)
• REVIEW: role in coronary artery disease (PMID:12235167)
• LIPC promoter is associated with a lowered HL activity and that this variation may contribute to the increased plasma HDL-C concentration (PMID:12364543)
• Results suggest that a T right curved arrow C substitution at -2 of the HL promoter may be associated with th e variation of HDL-cholesterol concentration and therefore affect the risk of CAD in Chinese. (PMID:12417924)
• REVIEW: potential impact of genetic determinants of hepatic lipase activity in modulating both the development of coronary and carotid atherosclerosis will be discussed based on hepatic lipase proposed roles in lipoprotein metabolism (PMID:12642787)
• Hepatic lipase C514T polymorphism and its relationship with coronary artery disease in Koreans. (PMID:12689525)
• the determinants of cell surface binding exist within the carboxyl terminal 70 amino acids of hepatic lipase, of which the last five residues play an important role (PMID:12700335)
• HL enzyme activities in 28 healthy subjects with well-controlled Type 1 diabetes, and their relationship with Lp(A-I) and Lp(A-I,A-II) (PMID:12777470)
• A174T and T383M mutations in exon 8 of the HL gene resulted in HL deficiency among the three related compound heterozygotes and was associated with a marked TG enrichment of LDL and HDL particles (PMID:12777476)
• Hepatic lipase promoter SNPs are associated with increased HDL cholesterol and, paradoxically, an increased risk of IHD after adjustment for HDL cholesterol, and particularly in individuals with apolipoprotein E epsilon43 genotype. (PMID:12798568)
• The HL gene may play an important role in the regulation of HDL-C levels from childhood to adulthood, especially in white males. (PMID:12860265)
• The TT genotype of HL mutation may serve as a protective factor against vascular disease by increasing HDL cholesterol levels in hemodialysis patients with higher CETP levels. (PMID:14531818)
• -514C>T polymorphism associates with plasma lipids according to dietary intake and ethnic background (PMID:14608050)
• Hepatic lipase has a direct role in regulating total plasma LDL concentrations as well as in the production of smaller, denser LDL from larger, more buoyant precursors. (PMID:14615390)
• white American men had higher hepatic lipase activity than black American and Japanese American men, related to ethnic differences in central adiposity but not LIPC allele frequency (PMID:14657196)
• hepatic lipase clears plasma cholesterol in LDL receptor-deficient “apoB-48-only” and “apoB-100-only” mice (PMID:14679168)
• ApoA-II appears to increase Hepatic Lipase association with HDL and inhibits lipid hydrolysis (PMID:14967812)
• role of C-480T polymorphism and serum HDL-cholesterol on risk of acute myocardial infarction in men (PMID:14985399)
• the -250G/A polymorphism in the HL gene is associated with significant variations in high-density lipoprotein C levels and coronary artery disease risk in males. (PMID:15099346)
• G-250G genotype of LIPC gene is risk factor for type 2 diabetes. Genes regulating lipid and lipoprotein metabolism may be potential candidate genes for type 2 diabetes. (PMID:15126514)
• -514C–>T gene polymorphism correlates with elevated fasting insulin concentrations in a German population. (PMID:15156410)
• High levels of catalytically active human hepatic lipase (HL) reduce atherosclerosis, whereas high levels of a catalytically inactive HL do not affect atherosclerosis in mice genetically deficient in low-density lipoprotein receptor and mouse HL. (PMID:15205216)
• hepatic lipase binds to heparan sulfate proteoglycans and has a profound HDL-lowering effect (PMID:15292235)
• This meta-analysis demonstrates the importance of the -514C–>T single nucleotide polymorphism in determining hepatic lipase activity and plasma HDL concentration and helps quantify the role that hepatic lipase plays in the metabolism of HDL cholesterol. (PMID:15292318)
• an anti-atherogenic role of the ligand-binding function of Hepatic lipase in vivo. (PMID:15304509)
• apoE increases the rate of HL-mediated phospholipid and triacylglycerol hydrolysis in rHDL (PMID:15379569)
• the opposite regulation of HL expression by fatty acids and statins is mediated via SREBP, possibly through interaction with upstream stimulatory factors (PMID:15721010)
• Effect of long-term hormone replacement therapy (HRT) on the progression of atherosclerosis in a 5-yr follow-up observational study of 88 postmenopausal women with different hepatic lipase genotypes. (PMID:15755868)
• Results show an improvement in insulin sensitivity in men with the -514T allele of the hepatic lipase promoter polymorphism, when monounsaturated fatty acids and carbohydrates are consumed instead of saturated fat. (PMID:15821100)
• The LIPC -514C allele was associated with higher hepatic lipase activity in sedentary and physically active states. (PMID:15983229)
• Polymorphic genotypes might increase the risk of developing diabetic nephropathy by slowing clearance of triglyceride-rich remnant lipoproteins (PMID:15983323)
• The LIPC promoter -514 C-T polymorphism is associated with a significantly reduced development of neointima after surgery. (PMID:16005462)
• Resuslts suggest that HL gene might be one of the important susceptibility genes of type 2 diabetes and the high incidence of type 2 diabetes could be explained by high frequency of -514T allele in the Japanese population. (PMID:16077949)
• HL activity was positively related with body mass index (P < 0.02) and waist/hip ratio (P < 0.05, multiple r = 0.74), but not with plasma adiponectin. (PMID:16122151)
• hepatic lipase (LIPC)-514TT genotype and overweight status, when occurring together, were associated with a 3-fold increase in risk of preeclampsia among Peruvian women (PMID:16316842)
• The influence of hepatic lipase C-480T polymorphism on coronary flow reserve in young men is independent of the plasma cholesterol level. (PMID:16330034)
• The -514C–>T polymorphism modulates the lipid-lowering response to bezafibrate, with a better effect in homozygous hyperlipemic subjects. (PMID:16338252)
• Plasma adiponectin levels are associated with increased hepatic lipase activity in Japanese hyperlipidemic men. (PMID:16419358)

Cross-species orthologs

19 orthologs

Organism	Symbol	Gene ID
danio_rerio	lipca	ENSDARG00000053476
danio_rerio	lipcb	ENSDARG00000090486
mus_musculus	Lipc	ENSMUSG00000032207
rattus_norvegicus	Lipc	ENSRNOG00000060338
drosophila_melanogaster	CG5162	FBGN0030828
drosophila_melanogaster	CG6675	FBGN0032973
drosophila_melanogaster	CG6472	FBGN0034166
drosophila_melanogaster	CG5665	FBGN0036977
drosophila_melanogaster	sxe2	FBGN0038398
drosophila_melanogaster	CG4582	FBGN0039344
drosophila_melanogaster	CG6296	FBGN0039470
drosophila_melanogaster	CG6295	FBGN0039471
drosophila_melanogaster	CG17192	FBGN0039472
drosophila_melanogaster	CG17191	FBGN0039473
drosophila_melanogaster	CG6283	FBGN0039474
drosophila_melanogaster	CG6277	FBGN0039475
drosophila_melanogaster	CG6271	FBGN0039476
drosophila_melanogaster	CG4267	FBGN0264979
drosophila_melanogaster	CG18258	FBGN0265267

Paralogs (9): LIPG (ENSG00000101670), PLA1A (ENSG00000144837), LIPH (ENSG00000163898), LPL (ENSG00000175445), PNLIP (ENSG00000175535), PNLIPRP1 (ENSG00000187021), LIPI (ENSG00000188992), PNLIPRP3 (ENSG00000203837), PNLIPRP2 (ENSG00000266200)

Protein

Protein identifiers

Hepatic triacylglycerol lipase — P11150 (reviewed: P11150)

Alternative names: Lipase member C, Lysophospholipase, Phospholipase A1

All UniProt accessions (3): E7EUJ1, E7EUK6, P11150

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of triglycerides and phospholipids present in circulating plasma lipoproteins, including chylomicrons, intermediate density lipoproteins (IDL), low density lipoproteins (LDL) of large size and high density lipoproteins (HDL), releasing free fatty acids (FFA) and smaller lipoprotein particles. Also exhibits lysophospholipase activity. Can hydrolyze both neutral lipid and phospholipid substrates but shows a greater binding affinity for neutral lipid substrates than phospholipid substrates. In native LDL, preferentially hydrolyzes the phosphatidylcholine species containing polyunsaturated fatty acids at sn-2 position.

Subunit / interactions. Homodimer.

Subcellular location. Secreted.

Disease relevance. Hepatic lipase deficiency (HL deficiency) [MIM:614025] A disorder characterized by elevated levels of beta-migrating very low density lipoproteins, and abnormally triglyceride-rich low and high density lipoproteins. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Phospholipase A1 and triacylglycerol lipase are inhibited by sphingomyelin.

Polymorphism. Genetic variations in LIPC define the high density lipoprotein cholesterol level quantitative trait locus 12 (HDLCQ12) [MIM:612797]. Genetic variations in LIPC are associated with susceptibility to type 2 diabetes mellitus (T2D) [MIM:125853].

Similarity. Belongs to the AB hydrolase superfamily. Lipase family.

RefSeq proteins (1): NP_000227* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000734	TAG_lipase	Family
IPR001024	PLAT/LH2_dom	Domain
IPR002333	Lipase_hep	Family
IPR013818	Lipase	Domain
IPR016272	Lipase_LIPH	Family
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR033906	Lipase_N	Domain
IPR036392	PLAT/LH2_dom_sf	Homologous_superfamily

Pfam: PF00151, PF01477

Catalyzed reactions (Rhea), 12 shown:

• a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H(+) (RHEA:12044)
• a 1-acyl-sn-glycero-3-phosphocholine + H2O = sn-glycerol 3-phosphocholine + a fatty acid + H(+) (RHEA:15177)
• a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 2-acyl-sn-glycero-3-phosphocholine + a fatty acid + H(+) (RHEA:18689)
• 1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = 2,3-di-(9Z)-octadecenoyl-sn-glycerol + (9Z)-octadecenoate + H(+) (RHEA:38391)
• 1,2-di-(9Z-octadecenoyl)-sn-glycerol + H2O = 2-(9Z-octadecenoyl)-glycerol + (9Z)-octadecenoate + H(+) (RHEA:38511)
• 1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = di-(9Z)-octadecenoylglycerol + (9Z)-octadecenoate + H(+) (RHEA:38575)
• 1,3-di-(9Z-octadecenoyl)-glycerol + H2O = 3-(9Z-octadecenoyl)-sn-glycerol + (9Z)-octadecenoate + H(+) (RHEA:38651)
• 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = (9Z-octadecenoyl)-sn-glycero-3-phosphocholine + (9Z)-octadecenoate + H(+) (RHEA:38699)
• 1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = sn-glycerol 3-phosphocholine + hexadecanoate + H(+) (RHEA:40435)
• 1,2,3-tributanoylglycerol + H2O = dibutanoylglycerol + butanoate + H(+) (RHEA:40475)
• 1-(9Z-octadecenoyl)-sn-glycero-3-phospho-L-serine + H2O = sn-glycero-3-phospho-L-serine + (9Z)-octadecenoate + H(+) (RHEA:40499)
• 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = hexadecanoyl-sn-glycero-3-phosphocholine + hexadecanoate + H(+) (RHEA:41384)

UniProt features (23 total): sequence variant 9, glycosylation site 4, active site 3, mutagenesis site 2, signal peptide 1, chain 1, domain 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11150-F1	82.03	0.61

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 (3): 168 (nucleophile); 194 (charge relay system); 279 (charge relay system)

Glycosylation sites (4): 397, 42, 78, 362

Mutagenesis-validated functional residues (2):

Position	Phenotype
255–276	loss of triglyceride hydrolase and phospholipase activity.
255–275	increased triglyceride hydrolase and reduced phospholipase activity.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-8963889	Assembly of active LPL and LIPC lipase complexes
R-HSA-8964026	Chylomicron clearance
R-HSA-174824	Plasma lipoprotein assembly, remodeling, and clearance
R-HSA-382551	Transport of small molecules
R-HSA-8963899	Plasma lipoprotein remodeling
R-HSA-8964043	Plasma lipoprotein clearance

MSigDB gene sets: 215 (showing top): MODULE_172, GOBP_ACYLGLYCEROL_HOMEOSTASIS, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, GOBP_STEROL_HOMEOSTASIS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, HNF1_Q6, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_LIPID_HOMEOSTASIS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_PLASMA_LIPOPROTEIN_PARTICLE_CLEARANCE, RGTTAMWNATT_HNF1_01

GO Biological Process (15): fatty acid biosynthetic process (GO:0006633), cholesterol metabolic process (GO:0008203), triglyceride catabolic process (GO:0019433), very-low-density lipoprotein particle remodeling (GO:0034372), intermediate-density lipoprotein particle remodeling (GO:0034373), low-density lipoprotein particle remodeling (GO:0034374), high-density lipoprotein particle remodeling (GO:0034375), chylomicron remnant clearance (GO:0034382), phosphatidylcholine catabolic process (GO:0034638), cholesterol homeostasis (GO:0042632), reverse cholesterol transport (GO:0043691), triglyceride homeostasis (GO:0070328), lipid metabolic process (GO:0006629), lipid catabolic process (GO:0016042), cholesterol transport (GO:0030301)

GO Molecular Function (13): lipoprotein lipase activity (GO:0004465), glycerophospholipase activity (GO:0004620), phosphatidylcholine lysophospholipase A1 activity (GO:0004622), triacylglycerol lipase activity (GO:0004806), heparin binding (GO:0008201), glycerophospholipid phospholipase A1 activity (GO:0008970), low-density lipoprotein particle binding (GO:0030169), apolipoprotein binding (GO:0034185), protein binding (GO:0005515), lipase activity (GO:0016298), hydrolase activity (GO:0016787), metal ion binding (GO:0046872), carboxylic ester hydrolase activity (GO:0052689)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), high-density lipoprotein particle (GO:0034364)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Plasma lipoprotein assembly, remodeling, and clearance	2
Plasma lipoprotein remodeling	1
Plasma lipoprotein clearance	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
triglyceride-rich lipoprotein particle remodeling	2
plasma lipoprotein particle remodeling	2
hydrolase activity, acting on ester bonds	2
fatty acid metabolic process	1
lipid biosynthetic process	1
monocarboxylic acid biosynthetic process	1
sterol metabolic process	1
secondary alcohol metabolic process	1
triglyceride metabolic process	1
acylglycerol catabolic process	1
triglyceride-rich lipoprotein particle clearance	1
phosphatidylcholine metabolic process	1
glycerophospholipid catabolic process	1
sterol homeostasis	1
cholesterol transport	1
acylglycerol homeostasis	1
primary metabolic process	1
lipid metabolic process	1
catabolic process	1
sterol transport	1
triacylglycerol lipase activity	1
phospholipase activity	1
lysophospholipase A1 activity	1
lipase activity	1
carboxylic ester hydrolase activity	1
glycosaminoglycan binding	1
sulfur compound binding	1
A1-type glycerophospholipase activity	1
lipoprotein particle binding	1
protein binding	1
binding	1
catalytic activity	1
cation binding	1
cellular anatomical structure	1
endoplasmic reticulum	1
intracellular organelle lumen	1
plasma lipoprotein particle	1

Protein interactions and networks

STRING

1588 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIPC	APOB	P04114	940
LIPC	LMF1	Q96S06	903
LIPC	CETP	P11597	891
LIPC	APOE	P02649	883
LIPC	APOA1	P02647	864
LIPC	PLTP	P55058	853
LIPC	LIPF	P07098	809
LIPC	APOC2	P02655	799
LIPC	LCAT	P04180	778
LIPC	APOC3	P02656	772
LIPC	GPIHBP1	Q8IV16	771
LIPC	APOA5	Q6Q788	768
LIPC	SCGB1D2	O95969	761
LIPC	ABCA1	O95477	737
LIPC	ARMS2	P0C7Q2	720

IntAct

5 interactions, top by confidence:

A	B	Type	Score
LIPC	ATP4A	psi-mi:“MI:0914”(association)	0.530
ZNF517	GGPS1	psi-mi:“MI:0914”(association)	0.530
ADHFE1	LIPC	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (10): ATP4A (Affinity Capture-MS), MTMR1 (Affinity Capture-MS), LIPC (Reconstituted Complex), LIPC (Reconstituted Complex), LIPC (Affinity Capture-MS), MTMR1 (Affinity Capture-MS), TTC7A (Affinity Capture-MS), ATP4A (Affinity Capture-MS), LMF1 (Affinity Capture-Western), LIPC (Two-hybrid)

ESM2 similar proteins: A1A4K5, A2BGL3, J3RZ81, O46559, O46647, P06858, P07867, P11150, P11151, P11152, P11153, P11602, P13612, P22413, P27656, P28825, P49060, P49923, P55031, P97535, Q06000, Q08761, Q13219, Q16819, Q29524, Q2TBF2, Q32PY2, Q3SZ79, Q53H76, Q5E9H0, Q5NDE3, Q5NDE4, Q5NDE5, Q5NDE8, Q5RBQ5, Q5XGE9, Q641F6, Q64230, Q64610, Q6DBU8

Diamond homologs: A0A0M3KKW3, A2VBC4, C0HLL3, O46559, P06857, P07867, P0CH47, P0CH86, P0CH87, P0DMB4, P0DMB5, P0DMB7, P0DMB8, P0DPT0, P0DSI2, P11150, P11602, P27656, P29183, P49369, P51528, P53357, P54315, P54316, P81139, Q02157, Q06478, Q3SZ79, Q3ZU95, Q5BKQ4, Q5XGE9, Q68KK0, Q6NYZ4, Q6Q249, Q6Q250, Q6Q251, Q6Q252, Q6XZB0, Q7M3V3, Q7M3V4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	192
Likely benign	74
Benign	52

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1174131	NM_000236.3(LIPC):c.1068= (p.Phe356=)	Pathogenic
1705275	NM_000236.3(LIPC):c.1052-1G>C	Pathogenic
29776	NM_000236.3(LIPC):c.583G>A (p.Ala195Thr)	Pathogenic
1705274	NM_000236.3(LIPC):c.748T>C (p.Phe250Leu)	Likely pathogenic

SpliceAI

2098 predictions. Top by Δscore:

Variant	Effect	Δscore
15:58538463:GGA:G	donor_gain	1.0000
15:58538464:GAG:G	donor_gain	1.0000
15:58538465:A:T	donor_gain	1.0000
15:58541780:CTCA:C	acceptor_loss	1.0000
15:58541781:TCAG:T	acceptor_loss	1.0000
15:58541782:CAGGT:C	acceptor_loss	1.0000
15:58541783:A:G	acceptor_loss	1.0000
15:58541783:AGGT:A	acceptor_gain	1.0000
15:58541784:G:GC	acceptor_loss	1.0000
15:58541784:GGTG:G	acceptor_gain	1.0000
15:58541938:G:GT	donor_gain	1.0000
15:58541965:G:GT	donor_gain	1.0000
15:58541966:AGGTA:A	donor_loss	1.0000
15:58541968:G:GA	donor_loss	1.0000
15:58548326:CCA:C	acceptor_loss	1.0000
15:58548327:CA:C	acceptor_loss	1.0000
15:58548328:A:AC	acceptor_loss	1.0000
15:58548328:A:AG	acceptor_gain	1.0000
15:58548329:G:A	acceptor_loss	1.0000
15:58548329:G:GG	acceptor_gain	1.0000
15:58548329:GCC:G	acceptor_gain	1.0000
15:58548569:AAAGG:A	donor_loss	1.0000
15:58548570:AAGG:A	donor_loss	1.0000
15:58548571:AGGTG:A	donor_loss	1.0000
15:58548572:GGTG:G	donor_loss	1.0000
15:58548574:T:A	donor_loss	1.0000
15:58556539:GA:G	donor_gain	1.0000
15:58556540:A:AG	donor_gain	1.0000
15:58556540:A:G	donor_gain	1.0000
15:58560859:TCTA:T	acceptor_loss	1.0000

AlphaMissense

3285 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:58545927:T:A	C254S	0.992
15:58545928:G:C	C254S	0.992
15:58548366:C:G	S282W	0.992
15:58548363:G:C	R281P	0.991
15:58545765:T:C	F200L	0.990
15:58545767:T:A	F200L	0.990
15:58545767:T:G	F200L	0.990
15:58545828:C:G	H221D	0.989
15:58548350:T:A	C277S	0.989
15:58548351:G:C	C277S	0.989
15:58542579:A:C	S168R	0.988
15:58542581:C:A	S168R	0.988
15:58542581:C:G	S168R	0.988
15:58541877:G:C	W122C	0.987
15:58541877:G:T	W122C	0.987
15:58542607:C:A	A177D	0.987
15:58548375:T:C	L285P	0.987
15:58541875:T:A	W122R	0.986
15:58541875:T:C	W122R	0.986
15:58542580:G:T	S168I	0.986
15:58545745:T:C	L193P	0.986
15:58545748:A:T	D194V	0.986
15:58545807:G:C	A214P	0.986
15:58542586:G:T	G170V	0.984
15:58545834:T:C	F223L	0.984
15:58545836:T:A	F223L	0.984
15:58545836:T:G	F223L	0.984
15:58545927:T:C	C254R	0.984
15:58545766:T:G	F200C	0.983
15:58548356:C:G	H279D	0.983

dbSNP variants (sampled 300 via entrez): RS1000008233 (15:58563831 C>T), RS1000012772 (15:58454008 A>G), RS1000030749 (15:58483163 T>A), RS1000034968 (15:58496085 T>C), RS1000062980 (15:58524797 T>C), RS1000097011 (15:58563687 A>G), RS1000100820 (15:58461606 T>C), RS1000172271 (15:58553517 T>G), RS1000177079 (15:58417665 T>C), RS1000179595 (15:58483551 C>T), RS1000208222 (15:58417417 A>T), RS1000227008 (15:58511848 C>A,T), RS1000240614 (15:58525179 C>A), RS1000279221 (15:58490695 T>C), RS1000291884 (15:58514261 A>G)

Disease associations

OMIM: gene MIM:151670 | disease phenotypes: MIM:614025, MIM:125853, MIM:125852

GenCC curated gene-disease

Disease	Classification	Inheritance
hyperlipidemia due to hepatic triglyceride lipase deficiency	Strong	Autosomal recessive

Mondo (3): hyperlipidemia due to hepatic triglyceride lipase deficiency (MONDO:0013533), type 2 diabetes mellitus (MONDO:0005148), type 1 diabetes mellitus 2 (MONDO:0007454)

Orphanet (1): Hyperlipidemia due to hepatic triacylglycerol lipase deficiency (Orphanet:140905)

HPO phenotypes

13 total (13 of 13 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000855	Insulin resistance
HP:0001013	Eruptive xanthomas
HP:0001084	Corneal arcus
HP:0001681	Angina pectoris
HP:0002155	Hypertriglyceridemia
HP:0003124	Hypercholesterolemia
HP:0003584	Late onset
HP:0005181	Premature coronary artery atherosclerosis
HP:0005978	Type II diabetes mellitus
HP:0012184	Increased HDL cholesterol concentration
HP:0031819	Increased waist to hip ratio

GWAS associations

336 associations (top):

Study	Trait	p-value
GCST000127_2	Amyotrophic lateral sclerosis	9.000000e-06
GCST000133_6	HDL cholesterol	2.000000e-32
GCST000135_5	HDL cholesterol	3.000000e-20
GCST000139_7	Triglycerides	2.000000e-08
GCST000274_3	Metabolite levels	1.000000e-07
GCST000284_5	HDL cholesterol	2.000000e-10
GCST000285_4	Cholesterol, total	4.000000e-07
GCST000288_2	HDL cholesterol	1.000000e-35
GCST000290_11	HDL cholesterol	8.000000e-23
GCST000533_30	Lipid metabolism phenotypes	9.000000e-15
GCST000533_4	Lipid metabolism phenotypes	1.000000e-19
GCST000533_5	Lipid metabolism phenotypes	4.000000e-16
GCST000579_10	Cognitive performance	2.000000e-06
GCST000583_28	Hematological and biochemical traits	1.000000e-14
GCST000653_10	Age-related macular degeneration	1.000000e-08
GCST000755_28	HDL cholesterol	3.000000e-96
GCST000758_11	Triglycerides	2.000000e-13
GCST000760_27	Cholesterol, total	9.000000e-20
GCST000805_1	HDL cholesterol	5.000000e-22
GCST000974_14	HDL cholesterol	1.000000e-09
GCST001007_16	Metabolic syndrome (bivariate traits)	6.000000e-08
GCST001007_9	Metabolic syndrome (bivariate traits)	1.000000e-08
GCST001100_1	Age-related macular degeneration	3.000000e-12
GCST001247_11	Cardiovascular disease risk factors	3.000000e-12
GCST001356_32	Gout	1.000000e-07
GCST001392_9	Lipid metabolism phenotypes	7.000000e-76
GCST001414_20	Phospholipid levels (plasma)	7.000000e-43
GCST001436_1	Metabolic syndrome	5.000000e-24
GCST001639_3	Metabolite levels	9.000000e-104
GCST001734_2	Non-small cell lung cancer	8.000000e-06

EFO canonical traits (28, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004574	total cholesterol measurement
EFO:0004529	lipid measurement
EFO:0003926	neuropsychological test
EFO:0000195	metabolic syndrome
EFO:0004723	coronary artery calcification
EFO:0004338	body weight
EFO:0004509	hemoglobin measurement
EFO:0004725	metabolite measurement
EFO:1001492	atrophic macular degeneration
EFO:0004458	C-reactive protein measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0009132	cholesterol efflux capacity measurement
EFO:0004329	alcohol drinking
EFO:0010225	lysophosphatidylethanolamine measurement
EFO:0010366	lysophosphatidylethanolamine 16:0 measurement
EFO:0007805	HDL cholesterol change measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004615	apolipoprotein B measurement
EFO:0007874	gut microbiome measurement
EFO:0004842	eosinophil count
EFO:0004348	hematocrit
EFO:0004587	lymphocyte count
EFO:0004305	erythrocyte count
EFO:0004736	aspartate aminotransferase measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003924	Diabetes Mellitus, Type 2	C18.452.394.750.149; C19.246.300
C565100	Diabetes Mellitus, Insulin-Dependent, 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2127 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 38,186 (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
CHEMBL175247	ORLISTAT	4	38,186

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1800588	Efficacy	3	fluvastatin;simvastatin
rs1800588	Efficacy	3	pravastatin

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1800588	LIPC	3	5.50	2	fluvastatin;simvastatin;pravastatin

Binding affinities (BindingDB)

226 measured of 340 human assays (340 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-[6-[4-(methoxymethyl)phenyl]-1,3-benzothiazol-2-yl]-2-methylsulfonyl-N-(2-sulfamoylethyl)acetamide	IC50	0.5 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-methoxyethyl N-[4-[2-[1-methylsulfonyl-2-oxo-2-(2-sulfamoylethylamino)ethyl]-1,3-benzothiazol-6-yl]phenyl]carbamate	IC50	0.5 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-[5-(6-methoxy-3-pyridinyl)-1,3-benzothiazol-2-yl]-2-methylsulfonyl-N-(2-sulfamoylethyl)acetamide	IC50	0.5 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-[5-(2-methoxy-4-pyridinyl)-1,3-benzothiazol-2-yl]-2-methylsulfonyl-N-(2-sulfamoylethyl)acetamide	IC50	0.5 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
N-(2-methoxyethyl)-4-[2-[1-methylsulfonyl-2-oxo-2-(2-sulfamoylethylamino)ethyl]-1,3-benzothiazol-5-yl]benzamide	IC50	0.5 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-[6-(3-fluoro-2-oxo-1H-pyridin-4-yl)-1,3-benzothiazol-2-yl]-2-methylsulfonyl-N-(2-sulfamoylethyl)acetamide	IC50	0.5 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
N-cyclopropyl-4-[2-[2-oxo-2-(2-sulfamoylethylamino)-1-[[4-(trifluoromethoxy)phenyl]methylsulfonyl]ethyl]-1,3-benzothiazol-6-yl]benzamide	IC50	0.5 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
4-[2-[2-oxo-2-(2-sulfamoylethylamino)-1-[[4-(trifluoromethoxy)phenyl]methylsulfonyl]ethyl]-1,3-benzothiazol-6-yl]benzamide	IC50	0.5 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-[5-(6-fluoro-3-pyridinyl)-1,3-benzothiazol-2-yl]-N-(2-sulfamoylethyl)-2-[[4-(trifluoromethoxy)phenyl]methylsulfonyl]acetamide	IC50	0.5 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-[5-(3-acetamidophenyl)-1,3-benzothiazol-2-yl]-2-methylsulfonyl-N-(2-sulfamoylethyl)acetamide	IC50	0.5 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-methylsulfonyl-2-[6-(3-phenoxyphenyl)-1,3-benzothiazol-2-yl]-N-(2-sulfamoylethyl)acetamide	IC50	0.6 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-[5-[4-(3,3-difluoroazetidine-1-carbonyl)phenyl]-1,3-benzothiazol-2-yl]-2-methylsulfonyl-N-(2-sulfamoylethyl)acetamide	IC50	0.6 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
N-(2-methoxyethyl)-4-[2-[2-oxo-2-(2-sulfamoylethylamino)-1-[[4-(trifluoromethoxy)phenyl]methylsulfonyl]ethyl]-1,3-benzothiazol-6-yl]benzamide	IC50	0.7 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
N-(3-hydroxypropyl)-4-[2-[1-methylsulfonyl-2-oxo-2-(2-sulfamoylethylamino)ethyl]-1,3-benzothiazol-6-yl]benzamide	IC50	0.7 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
4-[2-[1-(cyclopropylmethylsulfonyl)-2-oxo-2-(2-sulfamoylethylamino)ethyl]-1,3-benzothiazol-6-yl]-N-(2-methoxyethyl)-N-methylbenzamide	IC50	0.7 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-[6-[4-[(3S)-3-methoxypyrrolidine-1-carbonyl]phenyl]-1,3-benzothiazol-2-yl]-N-(2-sulfamoylethyl)-2-(3,3,3-trifluoropropylsulfonyl)acetamide	IC50	0.7 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-[6-[4-(3-fluoroazetidine-1-carbonyl)phenyl]-1,3-benzothiazol-2-yl]-2-methylsulfonyl-N-(2-sulfamoylethyl)acetamide	IC50	0.7 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-[5-[4-(methoxymethyl)phenyl]-1,3-benzothiazol-2-yl]-2-methylsulfonyl-N-(2-sulfamoylethyl)acetamide	IC50	0.7 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-[5-(2-fluoro-3-pyridinyl)-1,3-benzothiazol-2-yl]-2-methylsulfonyl-N-(2-sulfamoylethyl)acetamide	IC50	0.7 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-[6-(4-acetamidophenyl)-1,3-benzothiazol-2-yl]-N-(2-sulfamoylethyl)-2-(3,3,3-trifluoropropylsulfonyl)acetamide	IC50	0.8 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
4-[2-[1-(cyclopropylmethylsulfonyl)-2-oxo-2-(2-sulfamoylethylamino)ethyl]-1,3-benzothiazol-6-yl]-N-(2-methoxyethyl)benzamide	IC50	0.8 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-[6-(3-chlorophenyl)-1,3-benzothiazol-2-yl]-2-methylsulfonyl-N-(2-sulfamoylethyl)acetamide	IC50	0.8 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
N-(2-methoxyethyl)-N-methyl-4-[2-[2-oxo-2-(2-sulfamoylethylamino)-1-[[4-(trifluoromethyl)phenyl]methylsulfonyl]ethyl]-1,3-benzothiazol-6-yl]benzamide	IC50	0.8 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-[5-(2-fluorophenyl)-1,3-benzothiazol-2-yl]-2-methylsulfonyl-N-(2-sulfamoylethyl)acetamide	IC50	0.8 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-methylsulfonyl-2-(5-pyrimidin-2-yl-1,3-benzothiazol-2-yl)-N-(2-sulfamoylethyl)acetamide	IC50	0.8 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
4-[2-[1-(cyclopropylmethylsulfonyl)-2-oxo-2-(2-sulfamoylethylamino)ethyl]-1,3-benzothiazol-6-yl]-N-(2-methoxy-2-methylpropyl)benzamide	IC50	0.9 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-methylsulfonyl-2-[5-(6-oxo-1H-pyridin-3-yl)-1,3-benzothiazol-2-yl]-N-(2-sulfamoylethyl)acetamide	IC50	1 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-[(4-fluorophenyl)methylsulfonyl]-2-[5-(6-fluoro-3-pyridinyl)-1,3-benzothiazol-2-yl]-N-(2-sulfamoylethyl)acetamide	IC50	1 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
N-(2-hydroxy-2-methylpropyl)-3-[2-[2-oxo-2-(2-sulfamoylethylamino)-1-(3,3,3-trifluoropropylsulfonyl)ethyl]-1,3-benzothiazol-6-yl]benzamide	IC50	1 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-benzylsulfonyl-2-[5-methyl-6-[4-(piperidine-1-carbonyl)phenyl]-1,3-benzothiazol-2-yl]-N-(2-sulfamoylethyl)acetamide	IC50	1 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-[6-[1-(2-hydroxy-2-methylpropyl)-6-oxo-3-pyridinyl]-1,3-benzothiazol-2-yl]-2-methylsulfonyl-N-(2-sulfamoylethyl)acetamide	IC50	1.1 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
tert-butyl 4-[2-[1-benzylsulfonyl-2-oxo-2-(2-sulfamoylethylamino)ethyl]-1,3-benzothiazol-6-yl]benzoate	IC50	1.1 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-[5-(3-fluoro-4-pyridinyl)-1,3-benzothiazol-2-yl]-2-methylsulfonyl-N-(2-sulfamoylethyl)acetamide	IC50	1.1 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-methylsulfonyl-2-[6-(3-pyrrolidin-1-ylphenyl)-1,3-benzothiazol-2-yl]-N-(2-sulfamoylethyl)acetamide	IC50	1.2 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
4-[2-[1-[(3-cyanophenyl)methylsulfonyl]-2-oxo-2-(2-sulfamoylethylamino)ethyl]-1,3-benzothiazol-6-yl]-N-(2-methoxyethyl)benzamide	IC50	1.2 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-fluoro-N,N-dimethyl-4-[2-[1-methylsulfonyl-2-oxo-2-(2-sulfamoylethylamino)ethyl]-1,3-benzothiazol-6-yl]benzamide	IC50	1.2 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-[6-[4-(5-amino-1,3,4-thiadiazol-2-yl)phenyl]-1,3-benzothiazol-2-yl]-2-methylsulfonyl-N-(2-sulfamoylethyl)acetamide	IC50	1.2 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
4-[2-[1-benzylsulfonyl-2-oxo-2-(2-sulfamoylethylamino)ethyl]-5-methyl-1,3-benzothiazol-6-yl]benzoic acid	IC50	1.2 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-[5-(6-fluoro-3-pyridinyl)-1,3-benzothiazol-2-yl]-2-(2-methoxyethylsulfonyl)-N-(2-sulfamoylethyl)acetamide	IC50	1.3 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-[6-(4-chlorophenyl)-1,3-benzothiazol-2-yl]-2-methylsulfonyl-N-(2-sulfamoylethyl)acetamide	IC50	1.4 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
tert-butyl 4-[2-[1-benzylsulfonyl-2-oxo-2-(2-sulfamoylethylamino)ethyl]-5-methyl-1,3-benzothiazol-6-yl]benzoate	IC50	1.4 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
BDBM151558	IC50	1.5 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-[6-[3-(4-hydroxypiperidine-1-carbonyl)phenyl]-1,3-benzothiazol-2-yl]-N-(2-sulfamoylethyl)-2-(3,3,3-trifluoropropylsulfonyl)acetamide	IC50	1.5 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
4-[2-[1-methylsulfonyl-2-oxo-2-(2-sulfamoylethylamino)ethyl]-1,3-benzothiazol-6-yl]benzamide	IC50	1.6 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
4-[5-methyl-2-[1-methylsulfonyl-2-oxo-2-(2-sulfamoylethylamino)ethyl]-1,3-benzothiazol-6-yl]benzoic acid	IC50	1.6 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-[6-(3,5-difluoro-4-methoxyphenyl)-1,3-benzothiazol-2-yl]-2-methylsulfonyl-N-(2-sulfamoylethyl)acetamide	IC50	1.7 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
tert-butyl 4-[5-methyl-2-[1-methylsulfonyl-2-oxo-2-(2-sulfamoylethylamino)ethyl]-1,3-benzothiazol-6-yl]benzoate	IC50	1.7 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-[6-[4-(3-hydroxy-3-methylazetidine-1-carbonyl)phenyl]-1,3-benzothiazol-2-yl]-2-methylsulfonyl-N-(2-sulfamoylethyl)acetamide	IC50	1.8 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-[6-[4-[(3R)-3-hydroxypyrrolidine-1-carbonyl]phenyl]-1,3-benzothiazol-2-yl]-2-methylsulfonyl-N-(2-sulfamoylethyl)acetamide	IC50	1.8 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase
2-[5-[4-(2-methoxyethoxy)phenyl]-1,3-benzothiazol-2-yl]-2-methylsulfonyl-N-(2-sulfamoylethyl)acetamide	IC50	1.8 nM	US-8987314: Amide, urea or sulfone amide linked benzothiazole inhibitors of endothelial lipase

ChEMBL bioactivities

376 potent at pChembl≥5 of 386 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.30	IC50	0.5	nM	CHEMBL3677564
9.10	IC50	0.8	nM	CHEMBL3677604
9.10	IC50	0.8	nM	CHEMBL3677538
9.10	IC50	0.8	nM	CHEMBL3677562
9.10	IC50	0.8	nM	CHEMBL4460999
9.00	IC50	1	nM	CHEMBL3677630
9.00	IC50	1	nM	CHEMBL3672652
8.85	IC50	1.4	nM	CHEMBL3677580
8.82	IC50	1.5	nM	CHEMBL3677632
8.72	IC50	1.9	nM	CHEMBL3672654
8.72	IC50	1.9	nM	CHEMBL3677540
8.70	IC50	2	nM	CHEMBL4463265
8.68	IC50	2.1	nM	CHEMBL3682478
8.66	IC50	2.2	nM	CHEMBL3677434
8.62	IC50	2.4	nM	CHEMBL3677571
8.59	IC50	2.6	nM	CHEMBL3677610
8.59	IC50	2.6	nM	CHEMBL3672653
8.59	IC50	2.6	nM	CHEMBL3677433
8.55	IC50	2.8	nM	CHEMBL3677607
8.55	IC50	2.8	nM	CHEMBL3677537
8.55	IC50	2.8	nM	CHEMBL3677550
8.54	IC50	2.9	nM	CHEMBL3677608
8.52	IC50	3	nM	CHEMBL3677543
8.52	IC50	3	nM	CHEMBL3677601
8.52	IC50	3	nM	CHEMBL3890635
8.52	IC50	3	nM	ORLISTAT
8.44	IC50	3.6	nM	CHEMBL3677563
8.44	IC50	3.6	nM	CHEMBL3677545
8.44	IC50	3.6	nM	CHEMBL3677547
8.40	IC50	4	nM	CHEMBL4465833
8.40	IC50	4	nM	CHEMBL4460376
8.30	IC50	5	nM	CHEMBL3905549
8.29	IC50	5.1	nM	CHEMBL3677602
8.28	IC50	5.2	nM	CHEMBL3677548
8.27	IC50	5.4	nM	CHEMBL4587475
8.17	IC50	6.7	nM	CHEMBL3682490
8.15	IC50	7.1	nM	CHEMBL3677439
8.15	IC50	7	nM	CHEMBL4437751
8.14	IC50	7.3	nM	CHEMBL3677567
8.11	IC50	7.7	nM	CHEMBL3677553
8.05	IC50	9	nM	CHEMBL4471611
8.03	IC50	9.4	nM	CHEMBL3677581
8.00	IC50	10	nM	CHEMBL3677462
8.00	IC50	10	nM	CHEMBL3672632
8.00	IC50	10	nM	CHEMBL3677554
8.00	IC50	10	nM	CHEMBL3982030
8.00	IC50	10	nM	CHEMBL4446812
8.00	IC50	10	nM	CHEMBL4440746
7.96	IC50	11	nM	CHEMBL3677480
7.96	IC50	11	nM	CHEMBL3677465

PubChem BioAssay actives

63 with measured affinity, of 90 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
benzyl N-[4-[2-[1-cyano-2-[[2-(cyclopropylamino)-2-oxoethyl]amino]-2-oxoethyl]-1,3-benzothiazol-6-yl]phenyl]carbamate	1601381: Inhibition of hepatic lipase (unknown origin)	ic50	0.0008	uM
2-(6-phenyl-1,3-benzothiazole-2-carbonyl)-5-[(sulfamoylamino)methyl]-1,3,4-oxadiazole	1529150: Inhibition of human HL expressed in human COS7 cells using A10070 as substrate preincubated for 20 min followed by DMPG vesicle doped substrate addition and measured at 20 secs interval for 10 mins by fluorescence assay	ic50	0.0020	uM
2-[[methyl(sulfamoyl)amino]methyl]-5-(6-phenyl-1,3-benzothiazole-2-carbonyl)-1,3,4-oxadiazole	1529150: Inhibition of human HL expressed in human COS7 cells using A10070 as substrate preincubated for 20 min followed by DMPG vesicle doped substrate addition and measured at 20 secs interval for 10 mins by fluorescence assay	ic50	0.0030	uM
Orlistat	1586814: Inhibition of recombinant human HL expressed in COS7 cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins by fluorescence assay	ic50	0.0030	uM
4-[6-fluoro-2-[5-[(sulfamoylamino)methyl]-1,3,4-oxadiazole-2-carbonyl]-1,3-benzothiazol-5-yl]-N-(2,2,2-trifluoroethyl)benzamide	1529150: Inhibition of human HL expressed in human COS7 cells using A10070 as substrate preincubated for 20 min followed by DMPG vesicle doped substrate addition and measured at 20 secs interval for 10 mins by fluorescence assay	ic50	0.0040	uM
5-fluoro-2-[5-[(sulfamoylamino)methyl]-1,3,4-oxadiazole-2-carbonyl]-N-(2,2,2-trifluoroethyl)-1,3-benzothiazole-6-carboxamide	1529150: Inhibition of human HL expressed in human COS7 cells using A10070 as substrate preincubated for 20 min followed by DMPG vesicle doped substrate addition and measured at 20 secs interval for 10 mins by fluorescence assay	ic50	0.0040	uM
methyl N-[4-[2-[5-[(sulfamoylamino)methyl]-1,3,4-oxadiazole-2-carbonyl]-1,3-benzothiazol-6-yl]phenyl]carbamate	1529150: Inhibition of human HL expressed in human COS7 cells using A10070 as substrate preincubated for 20 min followed by DMPG vesicle doped substrate addition and measured at 20 secs interval for 10 mins by fluorescence assay	ic50	0.0050	uM
2-cyano-N-[2-(cyclopropylamino)-2-oxoethyl]-2-(6-phenyl-1,3-benzothiazol-2-yl)acetamide	1601381: Inhibition of hepatic lipase (unknown origin)	ic50	0.0054	uM
2-benzylsulfonyl-N-[2-(cyclopropylamino)-2-oxoethyl]-2-[6-(6-fluoro-3-pyridinyl)-1,3-benzothiazol-2-yl]acetamide	1591500: Inhibition of human hepatic lipase expressed in African green monkey COS7 cells using PED-A1 as substrate incubated for 20 mins and measured every 20 secs for 10 mins by FRET assay	ic50	0.0070	uM
2-[5-fluoro-6-(6-fluoro-3-pyridinyl)-1,3-benzothiazole-2-carbonyl]-5-[(sulfamoylamino)methyl]-1,3,4-oxadiazole	1529150: Inhibition of human HL expressed in human COS7 cells using A10070 as substrate preincubated for 20 min followed by DMPG vesicle doped substrate addition and measured at 20 secs interval for 10 mins by fluorescence assay	ic50	0.0090	uM
[5-[(methylsulfamoylamino)methyl]-1,3,4-oxadiazol-2-yl]-(6-phenyl-1,3-benzothiazol-2-yl)methanone	1529150: Inhibition of human HL expressed in human COS7 cells using A10070 as substrate preincubated for 20 min followed by DMPG vesicle doped substrate addition and measured at 20 secs interval for 10 mins by fluorescence assay	ic50	0.0100	uM
2-[6-(4-fluorophenyl)-1,3-benzothiazole-2-carbonyl]-5-[(sulfamoylamino)methyl]-1,3,4-oxadiazole	1529150: Inhibition of human HL expressed in human COS7 cells using A10070 as substrate preincubated for 20 min followed by DMPG vesicle doped substrate addition and measured at 20 secs interval for 10 mins by fluorescence assay	ic50	0.0100	uM
2-[(6-phenyl-1,3-benzothiazol-2-yl)-(3,3,3-trifluoropropylsulfonyl)methyl]-5-[(sulfamoylamino)methyl]-1,3,4-oxadiazole	1586814: Inhibition of recombinant human HL expressed in COS7 cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins by fluorescence assay	ic50	0.0100	uM
2-[benzylsulfonyl-[6-(3-chlorophenyl)-1,3-benzothiazol-2-yl]methyl]-5-[(sulfamoylamino)methyl]-1,3,4-oxadiazole	1586814: Inhibition of recombinant human HL expressed in COS7 cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins by fluorescence assay	ic50	0.0100	uM
2-[(6-phenyl-1,3-benzothiazol-2-yl)-propan-2-ylsulfonylmethyl]-5-[(sulfamoylamino)methyl]-1,3,4-oxadiazole	1586814: Inhibition of recombinant human HL expressed in COS7 cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins by fluorescence assay	ic50	0.0100	uM
2-[benzylsulfonyl-[6-(3,4-dichlorophenyl)-1,3-benzothiazol-2-yl]methyl]-5-[(sulfamoylamino)methyl]-1,3,4-oxadiazole	1586814: Inhibition of recombinant human HL expressed in COS7 cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins by fluorescence assay	ic50	0.0100	uM
5-[[5-[methylsulfonyl-(6-phenyl-1,3-benzothiazol-2-yl)methyl]-1,3,4-oxadiazol-2-yl]methyl]-1,3-thiazolidine-2,4-dione	1586814: Inhibition of recombinant human HL expressed in COS7 cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins by fluorescence assay	ic50	0.0100	uM
2-[2-methoxyethylsulfonyl-(6-phenyl-1,3-benzothiazol-2-yl)methyl]-5-[(sulfamoylamino)methyl]-1,3,4-oxadiazole	1586814: Inhibition of recombinant human HL expressed in COS7 cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins by fluorescence assay	ic50	0.0100	uM
2-methylsulfonyl-2-(6-phenyl-1,3-benzothiazol-2-yl)-N-(2-sulfamoylethyl)acetamide	1591500: Inhibition of human hepatic lipase expressed in African green monkey COS7 cells using PED-A1 as substrate incubated for 20 mins and measured every 20 secs for 10 mins by FRET assay	ic50	0.0150	uM
N-[3-(3,4-dichlorophenyl)propyl]-3-hydroxy-1-methyl-2-oxopyridine-4-carboxamide	1384995: Inhibition of recombinant human HL expressed in African green monkey COS7 cells using HDL as substrate pretreated for 10 mins followed by substrate addition and measured after 30 mins by LC/MS/MS analysis	ic50	0.0160	uM
2-[5-fluoro-6-(1-oxo-2,3-dihydroisoindol-5-yl)-1,3-benzothiazole-2-carbonyl]-5-[(sulfamoylamino)methyl]-1,3,4-oxadiazole	1529150: Inhibition of human HL expressed in human COS7 cells using A10070 as substrate preincubated for 20 min followed by DMPG vesicle doped substrate addition and measured at 20 secs interval for 10 mins by fluorescence assay	ic50	0.0200	uM
2-[6-(6-fluoro-3-pyridinyl)-1,3-benzothiazole-2-carbonyl]-5-[(sulfamoylamino)methyl]-1,3,4-oxadiazole	1529150: Inhibition of human HL expressed in human COS7 cells using A10070 as substrate preincubated for 20 min followed by DMPG vesicle doped substrate addition and measured at 20 secs interval for 10 mins by fluorescence assay	ic50	0.0200	uM
2-[6-fluoro-5-(1-oxo-2,3-dihydroisoindol-5-yl)-1,3-benzothiazole-2-carbonyl]-5-[(sulfamoylamino)methyl]-1,3,4-oxadiazole	1529150: Inhibition of human HL expressed in human COS7 cells using A10070 as substrate preincubated for 20 min followed by DMPG vesicle doped substrate addition and measured at 20 secs interval for 10 mins by fluorescence assay	ic50	0.0200	uM
2-[benzylsulfonyl-(6-phenyl-1,3-benzothiazol-2-yl)methyl]-5-[(sulfamoylamino)methyl]-1,3,4-oxadiazole	1586814: Inhibition of recombinant human HL expressed in COS7 cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins by fluorescence assay	ic50	0.0210	uM
2-(6-phenyl-1,3-benzothiazole-2-carbonyl)-5-[(1S)-1-(sulfamoylamino)ethyl]-1,3,4-oxadiazole	1529150: Inhibition of human HL expressed in human COS7 cells using A10070 as substrate preincubated for 20 min followed by DMPG vesicle doped substrate addition and measured at 20 secs interval for 10 mins by fluorescence assay	ic50	0.0300	uM
2-[6-(3-oxo-1,2-dihydroisoindol-5-yl)-1,3-benzothiazole-2-carbonyl]-5-[(sulfamoylamino)methyl]-1,3,4-oxadiazole	1529150: Inhibition of human HL expressed in human COS7 cells using A10070 as substrate preincubated for 20 min followed by DMPG vesicle doped substrate addition and measured at 20 secs interval for 10 mins by fluorescence assay	ic50	0.0300	uM
2-cyano-N-[2-(cyclopropylamino)-2-oxoethyl]-2-[6-[3-(piperidine-1-carbonyl)phenyl]-1,3-benzothiazol-2-yl]acetamide	1601381: Inhibition of hepatic lipase (unknown origin)	ic50	0.0350	uM
4-[2-fluoro-4-[5-fluoro-2-[5-[(sulfamoylamino)methyl]-1,3,4-oxadiazole-2-carbonyl]-1,3-benzothiazol-6-yl]benzoyl]morpholine	1529150: Inhibition of human HL expressed in human COS7 cells using A10070 as substrate preincubated for 20 min followed by DMPG vesicle doped substrate addition and measured at 20 secs interval for 10 mins by fluorescence assay	ic50	0.0400	uM
N-[2-(cyclopropylamino)-2-oxoethyl]-2-methylsulfonyl-2-(6-phenyl-1,3-benzothiazol-2-yl)acetamide	1591500: Inhibition of human hepatic lipase expressed in African green monkey COS7 cells using PED-A1 as substrate incubated for 20 mins and measured every 20 secs for 10 mins by FRET assay	ic50	0.0470	uM
2-methylsulfonyl-2-(6-phenyl-1,3-benzothiazol-2-yl)-N-(3-sulfamoylpropyl)acetamide	1591500: Inhibition of human hepatic lipase expressed in African green monkey COS7 cells using PED-A1 as substrate incubated for 20 mins and measured every 20 secs for 10 mins by FRET assay	ic50	0.0520	uM
5-methyl-5-[[5-[methylsulfonyl-(6-phenyl-1,3-benzothiazol-2-yl)methyl]-1,3,4-oxadiazol-2-yl]methyl]imidazolidine-2,4-dione	1586814: Inhibition of recombinant human HL expressed in COS7 cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins by fluorescence assay	ic50	0.0530	uM
2-[methylsulfonyl-(6-phenyl-1,3-benzothiazol-2-yl)methyl]-5-[(sulfamoylamino)methyl]-1,3,4-oxadiazole	1586814: Inhibition of recombinant human HL expressed in COS7 cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins by fluorescence assay	ic50	0.0530	uM
2-(6-phenyl-1,3-benzothiazole-2-carbonyl)-5-[(1R)-1-(sulfamoylamino)ethyl]-1,3,4-oxadiazole	1529150: Inhibition of human HL expressed in human COS7 cells using A10070 as substrate preincubated for 20 min followed by DMPG vesicle doped substrate addition and measured at 20 secs interval for 10 mins by fluorescence assay	ic50	0.0600	uM
2-cyano-N-[2-(cyclopropylamino)-2-oxoethyl]-2-[6-(1-oxo-2,3-dihydroisoindol-5-yl)-1,3-benzothiazol-2-yl]acetamide	1601381: Inhibition of hepatic lipase (unknown origin)	ic50	0.0700	uM
N-[3-(3,4-dichlorophenyl)propyl]-4-hydroxy-1-methyl-5-oxo-2H-pyrrole-3-carboxamide	1384995: Inhibition of recombinant human HL expressed in African green monkey COS7 cells using HDL as substrate pretreated for 10 mins followed by substrate addition and measured after 30 mins by LC/MS/MS analysis	ic50	0.0760	uM
N-[2-(cyclopropylamino)-2-oxoethyl]-2-[6-(6-fluoro-3-pyridinyl)-1,3-benzothiazol-2-yl]-2-(3,3,3-trifluoropropylsulfonyl)acetamide	1591500: Inhibition of human hepatic lipase expressed in African green monkey COS7 cells using PED-A1 as substrate incubated for 20 mins and measured every 20 secs for 10 mins by FRET assay	ic50	0.0790	uM
2-methylsulfonyl-2-(6-phenyl-1,3-benzothiazol-2-yl)-N-[2-(sulfamoylamino)ethyl]acetamide	1591500: Inhibition of human hepatic lipase expressed in African green monkey COS7 cells using PED-A1 as substrate incubated for 20 mins and measured every 20 secs for 10 mins by FRET assay	ic50	0.0810	uM
methyl N-[4-[2-[benzylsulfonyl-[5-[(sulfamoylamino)methyl]-1,3,4-oxadiazol-2-yl]methyl]-1,3-benzothiazol-6-yl]phenyl]carbamate	1586814: Inhibition of recombinant human HL expressed in COS7 cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins by fluorescence assay	ic50	0.0900	uM
4-[4-[2-[benzylsulfonyl-[5-[(sulfamoylamino)methyl]-1,3,4-oxadiazol-2-yl]methyl]-1,3-benzothiazol-6-yl]-2-chlorobenzoyl]morpholine	1586814: Inhibition of recombinant human HL expressed in COS7 cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins by fluorescence assay	ic50	0.1210	uM
N-[2-(cyclopropylamino)-2-oxoethyl]-2-[6-(6-fluoro-3-pyridinyl)-1,3-benzothiazol-2-yl]-2-methylsulfonylacetamide	1591500: Inhibition of human hepatic lipase expressed in African green monkey COS7 cells using PED-A1 as substrate incubated for 20 mins and measured every 20 secs for 10 mins by FRET assay	ic50	0.1300	uM
2-[6-[4-(azetidine-1-carbonyl)phenyl]-1,3-benzothiazol-2-yl]-2-cyano-N-[2-(cyclopropylamino)-2-oxoethyl]acetamide	1601381: Inhibition of hepatic lipase (unknown origin)	ic50	0.1700	uM
2-cyano-2-[6-(6-fluoro-3-pyridinyl)-1,3-benzothiazol-2-yl]-N-[2-(oxetan-3-ylamino)-2-oxoethyl]acetamide	1601381: Inhibition of hepatic lipase (unknown origin)	ic50	0.1900	uM
N-[2-(cyclopropylamino)-2-oxoethyl]-2-[6-(6-fluoro-3-pyridinyl)-1,3-benzothiazol-2-yl]-2-(2-methoxyethylsulfonyl)acetamide	1591500: Inhibition of human hepatic lipase expressed in African green monkey COS7 cells using PED-A1 as substrate incubated for 20 mins and measured every 20 secs for 10 mins by FRET assay	ic50	0.2300	uM
2-cyano-N-(2-oxo-2-pyrrolidin-1-ylethyl)-2-(6-phenyl-1,3-benzothiazol-2-yl)acetamide	1601381: Inhibition of hepatic lipase (unknown origin)	ic50	0.2500	uM
2-methylsulfonyl-2-[6-[4-(morpholine-4-carbonyl)phenyl]-1,3-benzothiazol-2-yl]-N-(2-sulfamoylethyl)acetamide	1591500: Inhibition of human hepatic lipase expressed in African green monkey COS7 cells using PED-A1 as substrate incubated for 20 mins and measured every 20 secs for 10 mins by FRET assay	ic50	0.2800	uM
2-cyano-N-[2-(cyclopropylamino)-2-oxoethyl]-2-[6-[4-(morpholine-4-carbonyl)phenyl]-1,3-benzothiazol-2-yl]acetamide	1601381: Inhibition of hepatic lipase (unknown origin)	ic50	0.3000	uM
2-methylsulfonyl-2-[6-[1-(2-morpholin-4-ylethyl)pyrazol-4-yl]-1,3-benzothiazol-2-yl]-N-(2-sulfamoylethyl)acetamide	1591500: Inhibition of human hepatic lipase expressed in African green monkey COS7 cells using PED-A1 as substrate incubated for 20 mins and measured every 20 secs for 10 mins by FRET assay	ic50	0.3100	uM
4-[2-[benzylsulfonyl-[5-[(sulfamoylamino)methyl]-1,3,4-oxadiazol-2-yl]methyl]-1,3-benzothiazol-6-yl]-2-chloro-N,N-dimethylbenzamide	1586814: Inhibition of recombinant human HL expressed in COS7 cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins by fluorescence assay	ic50	0.3910	uM
2-cyano-N-[2-(cyclopropylamino)-2-oxoethyl]-2-[6-(3-oxo-1,2-dihydroisoindol-5-yl)-1,3-benzothiazol-2-yl]acetamide	1601381: Inhibition of hepatic lipase (unknown origin)	ic50	0.4200	uM
5-[[5-[methylsulfonyl-[6-[4-(morpholine-4-carbonyl)phenyl]-1,3-benzothiazol-2-yl]methyl]-1,3,4-oxadiazol-2-yl]methyl]-1,3-thiazolidine-2,4-dione	1586814: Inhibition of recombinant human HL expressed in COS7 cells using PED-A1 containing DMPG vesicles as substrate pretreated for 20 mins followed by substrate addition and measured every 20 secs for 10 mins by fluorescence assay	ic50	0.4500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, decreases expression	4
Cyclosporine	decreases expression, increases expression, affects cotreatment	4
bisphenol A	affects cotreatment, affects expression, increases expression	3
Tetrachlorodibenzodioxin	increases expression	3
Acetaminophen	decreases expression, affects cotreatment	2
Cholesterol, HDL	affects abundance, affects reaction	2
Valproic Acid	increases expression, increases methylation, decreases expression	2
Oleic Acid	affects cotreatment, increases expression, decreases expression, decreases reaction	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
bisphenol F	affects cotreatment, increases expression	1
methyleugenol	decreases expression	1
pirinixic acid	increases expression, affects binding, increases activity	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
ciglitazone	increases expression, affects binding	1
nefazodone	affects cotreatment, decreases expression	1
GW 4064	decreases expression, affects cotreatment	1
GW 501516	affects binding, increases expression	1
bazedoxifene	increases expression	1
obeticholic acid	decreases expression	1
6-(4-chlorophenyl)imidazo(2,1-b)(1,3)thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime	affects cotreatment, increases expression	1
chiglitazar	increases expression	1
3-hydroxy-4-prenyl-5-methoxystilbene-2-carboxylic acid	increases expression	1
(+)-JQ1 compound	decreases expression	1
Atazanavir Sulfate	decreases expression, affects cotreatment	1
Rosiglitazone	increases expression	1
Sorafenib	decreases expression, decreases reaction	1

ChEMBL screening assays

12 unique, capped per target: 11 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1015041	Binding	Inhibition of hepatic lipase activity assessed as release of free fatty acid from hydrolysis of VLDL by cell based assay	Design, synthesis, and biological evaluation of (2R,alphaS)-3,4-dihydro-2-[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-5-[3-(trifluoromethoxy)-phenyl]-alpha-(trifluoromethyl)-1(2H)-quinolineethanol as potent and orally active cholesteryl ester transfer protein inhibitor. — J Med Chem
CHEMBL4400383	ADMET	Inhibition of hepatic lipase (unknown origin)	Benzothiazole-based compounds as potent endothelial lipase inhibitors. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00006163	PHASE4	COMPLETED	Computer-assisted Diabetes Self-management Interventions
NCT00036504	PHASE4	COMPLETED	Efficacy and Safety of Twice-Daily Insulin Lispro Low Mixture Compared to a Once-Daily Long Acting Insulin Comparator in Patients Who Have Been Using One or More Oral Antihyperglycemic Agents Without Insulin
NCT00044460	PHASE4	COMPLETED	Efficacy and Safety In Poorly Controlled Type 2 Diabetics
NCT00095446	PHASE4	COMPLETED	NovoLog Observation Trial in Subjects With Type 1 and Type 2 Diabetes
NCT00101751	PHASE4	COMPLETED	INITIATE Plus (INITiation of Insulin to Reach A1c TargEt) Study
NCT00110370	PHASE4	COMPLETED	Comparing Pre-Mixed Insulin With Insulin Glargine Combined With Rapid-Acting Insulin in Patients With Type 2 Diabetes
NCT00110448	PHASE4	COMPLETED	Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial
NCT00118950	PHASE4	COMPLETED	Effect of Metformin Versus Repaglinide Treatment in Non-Obese Type 2 Diabetic Patients Uncontrolled by Diet
NCT00118963	PHASE4	COMPLETED	Effect of Repaglinide Versus Metformin Treatment in Non-Obese Patients With Type-2-Diabetes
NCT00121966	PHASE4	COMPLETED	South Danish Diabetes Study: Evaluation of the Antidiabetic Treatment of Type 2 Diabetes Mellitus
NCT00123604	PHASE4	COMPLETED	Vascular Effects of Carvedilol Versus Metoprolol in Hypertensive Patients With Type 2 Diabetes
NCT00123643	PHASE4	COMPLETED	Vascular Effects of Rosiglitazone Versus Glyburide in Type 2 Diabetic Patients
NCT00124397	PHASE4	COMPLETED	Atorvastatin and Endothelial Function in Type 2 Diabetes Mellitus (ATTEND-Study)
NCT00129233	PHASE4	COMPLETED	Comparison of Valsartan With Amlodipine in Hypertensive Patients With Glucose Intolerance
NCT00133718	PHASE4	COMPLETED	A 2 Year Trial of Patients With Type 2 Diabetes Focusing on Cardiovascular Diagnostics and Metabolic Control
NCT00135070	PHASE4	TERMINATED	Hospital In-Patient Insulin Study
NCT00141232	PHASE4	COMPLETED	Evaluating Atorvastatin With Omega-3 Fatty Acids in Cardiovascular Risk Reduction in Patients With Type 2 Diabetes
NCT00144144	PHASE4	UNKNOWN	A Study on Ca Blocker Versus AII Antagonists in Hypertension With Type 2 Diabetes
NCT00149331	PHASE4	COMPLETED	The Effects of Two Education Strategies About Insulin on Patient Preferences and Perceptions About Insulin Therapy
NCT00162357	PHASE4	COMPLETED	Post-PCI:Cardiac Imaging in Patients With Diabetes to Detect Coronary Artery Blockages Previously Opened by Angioplasty
NCT00174681	PHASE4	COMPLETED	Tulip Study: Testing the Usefulness of Lantus When Initiated Prematurely In Patients With Type 2 Diabetes
NCT00174824	PHASE4	COMPLETED	Comparison of Insulin Glargine and NPH Human Insulin in Progression of Diabetic Retinopathy in Type 2 Diabetic Patients
NCT00177398	PHASE4	COMPLETED	Effect of Glargine Insulin on Glucose Control in Hospitalized Patients Who Receive Tube Feedings
NCT00179400	PHASE4	COMPLETED	The Role of Acute Combined PPAR Alpha and Gamma Stimulation on Insulin Action in Humans
NCT00184561	PHASE4	COMPLETED	Effectiveness and Safety of Biphasic Insulin Aspart 70/30 in Subjects With Type 2 Diabetes
NCT00184626	PHASE4	COMPLETED	Comparison of Insulin Glargine Versus Biphasic Insulin Aspart 30/70 or Biphasic Insulin Aspart 30/70 in Combination With Metformin in Subjects With Type 2 Diabetes.
NCT00191178	PHASE4	COMPLETED	Effects of Insulin in Perceived Mood Symptoms in Patients With Type 2 Diabetes
NCT00191282	PHASE4	COMPLETED	Hyperglycemia and Cardiovascular Outcomes With Type 2 Diabetes
NCT00191464	PHASE4	COMPLETED	Long-Term Effects of Insulin Plus Metformin Regimens on the Overall and Postprandial Glycemic Control of Patients With Type 2 Diabetes
NCT00192803	PHASE4	UNKNOWN	Non-Insulin Dependent Diabetes Mellitus (NIDDM) and Angiotensin Converting Enzyme 2 (ACE2): Diabetic Patients Treated With Antihypertensive Drugs
NCT00202033	PHASE4	COMPLETED	Impact of Self-Monitoring Blood Glucose Frequency on Glycemic Control in Patients With Type 2 Diabetes
NCT00205660	PHASE4	COMPLETED	Changes in Adiposity, Metabolic Measures From Atypicals to Aripiprazole
NCT00212290	PHASE4	COMPLETED	Insulin Resistance and Central Nervous System (CNS) Function in Type 2 Diabetes
NCT00212303	PHASE4	COMPLETED	Exercise Training in Type 2 Diabetes and Hypertension
NCT00225342	PHASE4	WITHDRAWN	Study Protocol for Rosiglitazone Versus Gliclazide in Diabetics With Angina
NCT00238472	PHASE4	COMPLETED	A Pilot Study to Evaluate the Effects of Nateglinide vs. Glibenclamide on Renal Hemodynamics and Albumin Excretion
NCT00239538	PHASE4	COMPLETED	SMOOTH - Blood Pressure Control in Diabetic/Obese Patients
NCT00240253	PHASE4	COMPLETED	A Study Evaluating the Efficacy and Safety of Adding Symlin® to Lantus® (Insulin Glargine) in Subjects With Type 2 Diabetes
NCT00240422	PHASE4	COMPLETED	Trial to Compare the Effects of Either Telmisartan (40-80 mg PO Once Daily) or Ramipril (5-10 mg PO Once Daily) on Renal Endothelial Dysfunction in Hypertensive Patients With Type 2 Diabetes
NCT00241085	PHASE4	COMPLETED	Effect of Valsartan on Proteinuria in Patients With Hypertension and Diabetes Mellitus