Plant Name: Xanthium sibiricum
Collective Molecular Activities at 10μM Activity Cutoff
List of Human Proteins Collectively Targeted by the Plant
Click Gene ID to Access Activity Profile of Individual Target
| TSHR; | |
| FFAR1; FFAR4; HCAR2; | |
| PTPN1; | |
| GAA; | |
| TDP1; PKM; HPGD; AKR1B1; HSD17B10; AKR1B10; ALOX15; POLB; | |
| CA2; CA1; CA12; CA9; CA7; CA14; CA3; CA5B; CA5A; CA4; CA6; | |
| PPARA; PPARD; PPARG; | |
| KDM4E; | |
| MMP9; MMP1; MMP2; | |
| TLR2; | |
| HIF1A; NFKB1; | |
| RAB9A; LMNA; FABP3; FABP5; FABP2; FABP4; MAPT; APP; | |
| L3MBTL1; |
List of Human Cytochrome P450 Enzymes Affected by the Plant
Click Gene ID to Access Activity Profile of Individual Enzyme
| Cytochrome P450 Enzymes: |
|---|
Detailed Information of Human Protein Targets
| Protein Class | Gene ID | Protein Name | Uniprot ID | Target ChEMBL ID |
|---|---|---|---|---|
| Enzyme_unclassified | POLB | DNA polymerase beta | P06746 | CHEMBL2392 |
| Enzyme_unclassified | TDP1 | Tyrosyl-DNA phosphodiesterase 1 | Q9NUW8 | CHEMBL1075138 |
| Enzyme_unclassified | PKM | Pyruvate kinase isozymes M1/M2 | P14618 | CHEMBL1075189 |
| Enzyme_unclassified | HPGD | 15-hydroxyprostaglandin dehydrogenase [NAD+] | P15428 | CHEMBL1293255 |
| Enzyme_unclassified | AKR1B1 | Aldose reductase | P15121 | CHEMBL1900 |
| Enzyme_unclassified | HSD17B10 | Endoplasmic reticulum-associated amyloid beta-peptide-binding protein | Q99714 | CHEMBL4159 |
| Enzyme_unclassified | AKR1B10 | Aldo-keto reductase family 1 member B10 | O60218 | CHEMBL5983 |
| Enzyme_unclassified | ALOX15 | Arachidonate 15-lipoxygenase | P16050 | CHEMBL2903 |
| Hydrolase | GAA | Lysosomal alpha-glucosidase | P10253 | CHEMBL2608 |
| Lyase | CA2 | Carbonic anhydrase II | P00918 | CHEMBL205 |
| Lyase | CA1 | Carbonic anhydrase I | P00915 | CHEMBL261 |
| Lyase | CA12 | Carbonic anhydrase XII | O43570 | CHEMBL3242 |
| Lyase | CA9 | Carbonic anhydrase IX | Q16790 | CHEMBL3594 |
| Lyase | CA7 | Carbonic anhydrase VII | P43166 | CHEMBL2326 |
| Lyase | CA14 | Carbonic anhydrase XIV | Q9ULX7 | CHEMBL3510 |
| Lyase | CA3 | Carbonic anhydrase III | P07451 | CHEMBL2885 |
| Lyase | CA5B | Carbonic anhydrase VB | Q9Y2D0 | CHEMBL3969 |
| Lyase | CA5A | Carbonic anhydrase VA | P35218 | CHEMBL4789 |
| Lyase | CA4 | Carbonic anhydrase IV | P22748 | CHEMBL3729 |
| Lyase | CA6 | Carbonic anhydrase VI | P23280 | CHEMBL3025 |
| Lysine demethylase | KDM4E | Lysine-specific demethylase 4D-like | B2RXH2 | CHEMBL1293226 |
| Metallo protease | MMP9 | Matrix metalloproteinase 9 | P14780 | CHEMBL321 |
| Metallo protease | MMP1 | Matrix metalloproteinase-1 | P03956 | CHEMBL332 |
| Metallo protease | MMP2 | Matrix metalloproteinase-2 | P08253 | CHEMBL333 |
| Methyl-lysine/arginine binding protein | L3MBTL1 | Lethal(3)malignant brain tumor-like protein 1 | Q9Y468 | CHEMBL1287622 |
| Nuclear hormone receptor subfamily 1 group C | PPARA | Peroxisome proliferator-activated receptor alpha | Q07869 | CHEMBL239 |
| Nuclear hormone receptor subfamily 1 group C | PPARD | Peroxisome proliferator-activated receptor delta | Q03181 | CHEMBL3979 |
| Nuclear hormone receptor subfamily 1 group C | PPARG | Peroxisome proliferator-activated receptor gamma | P37231 | CHEMBL235 |
| Peptide receptor (family A GPCR) | TSHR | Thyroid stimulating hormone receptor | P16473 | CHEMBL1963 |
| Protein Phosphatase | PTPN1 | Protein-tyrosine phosphatase 1B | P18031 | CHEMBL335 |
| Small molecule receptor (family A GPCR) | FFAR1 | Free fatty acid receptor 1 | O14842 | CHEMBL4422 |
| Small molecule receptor (family A GPCR) | FFAR4 | G-protein coupled receptor 120 | Q5NUL3 | CHEMBL5339 |
| Small molecule receptor (family A GPCR) | HCAR2 | Hydroxycarboxylic acid receptor 2 | Q8TDS4 | CHEMBL3785 |
| Toll-like and Il-1 receptors | TLR2 | Toll-like receptor 2 | O60603 | CHEMBL4163 |
| Transcription Factor | HIF1A | Hypoxia-inducible factor 1 alpha | Q16665 | CHEMBL4261 |
| Transcription Factor | NFKB1 | Nuclear factor NF-kappa-B p105 subunit | P19838 | CHEMBL3251 |
| Unclassified | RAB9A | Ras-related protein Rab-9A | P51151 | CHEMBL1293294 |
| Unclassified | LMNA | Prelamin-A/C | P02545 | CHEMBL1293235 |
| Unclassified | FABP3 | Fatty acid binding protein muscle | P05413 | CHEMBL3344 |
| Unclassified | FABP5 | Fatty acid binding protein epidermal | Q01469 | CHEMBL3674 |
| Unclassified | FABP2 | Fatty acid binding protein intestinal | P12104 | CHEMBL4879 |
| Unclassified | FABP4 | Fatty acid binding protein adipocyte | P15090 | CHEMBL2083 |
| Unclassified | MAPT | Microtubule-associated protein tau | P10636 | CHEMBL1293224 |
| Unclassified | APP | Beta amyloid A4 protein | P05067 | CHEMBL2487 |
Enrichment of Gene Ontology of Target Proteins (Activity≤10μM)
Detailed Information of Enriched Gene Ontolgy
| GO Type | GO Category | Enriched GO Terms | p-Value | Adjusted p-Value | Enriched Genes |
|---|---|---|---|---|---|
| MF | GO:0005488; binding | GO:0008270; zinc ion binding | 5.245E-14 | 1.142E-10 | CA1, CA12, CA2, CA3, CA4, CA5A, CA5B, CA6, CA7, CA9, L3MBTL1, MMP1, MMP2, MMP9, PPARA, PPARD, PPARG, PTPN1 |
| BP | GO:0008152; metabolic process | GO:0019433; triglyceride catabolic process | 2.860E-07 | 1.946E-04 | FABP2, FABP3, FABP4, FABP5 |
| BP | GO:0050896; response to stimulus | GO:0001666; response to hypoxia | 1.803E-06 | 9.130E-04 | HIF1A, LMNA, MMP2, PKM, PPARA, PPARD, TLR2 |
| MF | GO:0003824; catalytic activity | GO:0004089; carbonate dehydratase activity | 2.982E-27 | 6.493E-23 | CA1, CA12, CA14, CA2, CA3, CA4, CA5A, CA5B, CA6, CA7, CA9 |
| BP | GO:0009987; cellular process | GO:0033554; cellular response to stress | 4.292E-06 | 1.797E-03 | AKR1B1, ALOX15, CA2, CA9, HIF1A, LMNA, MAPT, MMP9, NFKB1, POLB, PPARD, PPARG, PTPN1, TDP1 |
| BP | GO:0050896; response to stimulus | GO:0050728; negative regulation of inflammatory response | 6.184E-06 | 2.448E-03 | FFAR4, NFKB1, PPARA, PPARD, PPARG |
| BP | GO:0050896; response to stimulus | GO:1901653; cellular response to peptide | 7.280E-06 | 2.831E-03 | AKR1B1, APP, NFKB1, PKM, PPARG, TSHR |
| BP | GO:0032501; multicellular organismal process | GO:0014005; microglia development | 1.519E-05 | 4.865E-03 | APP, TLR2 |
| BP | GO:0009987; cellular process | GO:0032849; positive regulation of cellular pH reduction | 1.519E-05 | 4.865E-03 | CA2, CA7 |
| BP | GO:0050896; response to stimulus | GO:0032868; response to insulin | 1.556E-05 | 4.910E-03 | FABP3, PKM, PPARA, PPARG, TLR2 |
| BP | GO:0051179; localization | GO:0015908; fatty acid transport | 1.617E-05 | 5.029E-03 | FABP3, PPARA, PPARD, PPARG |
| BP | GO:0008283; cell proliferation | GO:1904707; positive regulation of vascular smooth muscle cell proliferation | 1.648E-05 | 5.053E-03 | HPGD, MMP2, MMP9 |
| BP | GO:0008152; metabolic process | GO:0055114; oxidation-reduction process | 2.632E-05 | 7.539E-03 | AKR1B1, AKR1B10, ALOX15, GAA, HPGD, HSD17B10, KDM4E, PKM, PPARD, PPARG |
| BP | GO:0032501; multicellular organismal process | GO:0032640; tumor necrosis factor production | 3.034E-05 | 8.056E-03 | APP, TLR2 |
| BP | GO:0050896; response to stimulus | GO:0070542; response to fatty acid | 3.265E-05 | 8.463E-03 | FABP3, FFAR1, PPARG, TLR2 |
| BP | GO:0008152; metabolic process | GO:0032963; collagen metabolic process | 3.429E-05 | 8.724E-03 | HIF1A, MMP1, MMP2, MMP9 |
| BP | GO:0008152; metabolic process | GO:0046320; regulation of fatty acid oxidation | 3.472E-05 | 8.724E-03 | FABP3, PPARA, PPARG |
| BP | GO:0050896; response to stimulus | GO:0042493; response to drug | 3.486E-05 | 8.724E-03 | AKR1B1, CA3, CA9, FABP3, HPGD, NFKB1, POLB, PPARG, TLR2 |
| BP | GO:0065007; biological regulation | GO:0048878; chemical homeostasis | 4.141E-05 | 9.909E-03 | AKR1B1, APP, CA12, CA2, CA7, FABP3, FABP4, FFAR1, HIF1A, PPARG |
| BP | GO:0051179; localization | GO:0015701; bicarbonate transport | 1.601E-20 | 1.743E-16 | CA1, CA12, CA14, CA2, CA3, CA4, CA5A, CA5B, CA6, CA7, CA9 |
| BP | GO:0008152; metabolic process | GO:0006730; one-carbon metabolic process | 3.043E-19 | 1.325E-15 | CA1, CA12, CA2, CA3, CA4, CA5A, CA5B, CA6, CA7, CA9 |
Enriched KEGG Pathways of Target Proteins (Activity≤10μM)
Top 10, ordered by adjusted p-value
Detailed Information of Enriched KEGG Pathways
| Pathway ID | Pathway Name | p-Value | Adjusted p-Value | Enriched Genes |
|---|---|---|---|---|
| hsa00910 | Nitrogen metabolism_Homo sapiens_hsa00910 | 1.838E-26 | 1.967E-24 | CA12; CA1; CA3; CA5B; CA2; CA5A; CA4; CA7; CA6; CA9; CA14 |
| hsa03320 | PPAR signaling pathway_Homo sapiens_hsa03320 | 2.120E-12 | 1.134E-10 | FABP2; FABP3; FABP4; FABP5; MMP1; PPARG; PPARA; PPARD |
| hsa05200 | Pathways in cancer_Homo sapiens_hsa05200 | 2.343E-05 | 8.355E-04 | MMP1; MMP2; PPARG; HIF1A; MMP9; NFKB1; PPARD |
| hsa05219 | Bladder cancer_Homo sapiens_hsa05219 | 9.989E-05 | 2.138E-03 | MMP1; MMP2; MMP9 |
| hsa00052 | Galactose metabolism_Homo sapiens_hsa00052 | 3.869E-05 | 1.035E-03 | AKR1B10; GAA; AKR1B1 |
| hsa05205 | Proteoglycans in cancer_Homo sapiens_hsa05205 | 1.018E-03 | 1.362E-02 | MMP2; HIF1A; MMP9; TLR2 |
| hsa04024 | cAMP signaling pathway_Homo sapiens_hsa04024 | 9.456E-04 | 1.362E-02 | HCAR2; PPARA; NFKB1; TSHR |
| hsa05202 | Transcriptional misregulation in cancer_Homo sapiens_hsa05202 | 6.503E-04 | 1.160E-02 | HPGD; PPARG; MMP9; NFKB1 |
| hsa04931 | Insulin resistance_Homo sapiens_hsa04931 | 1.773E-03 | 1.897E-02 | PTPN1; PPARA; NFKB1 |
| hsa05162 | Measles_Homo sapiens_hsa05162 | 3.322E-03 | 2.735E-02 | RAB9A; NFKB1; TLR2 |
| hsa05161 | Hepatitis B_Homo sapiens_hsa05161 | 4.055E-03 | 3.099E-02 | MMP9; NFKB1; TLR2 |
| hsa05010 | Alzheimer's disease_Homo sapiens_hsa05010 | 5.990E-03 | 4.156E-02 | APP; MAPT; HSD17B10 |
| hsa00040 | Pentose and glucuronate interconversions_Homo sapiens_hsa00040 | 2.842E-03 | 2.534E-02 | AKR1B10; AKR1B1 |
| hsa04964 | Proximal tubule bicarbonate reclamation_Homo sapiens_hsa04964 | 1.162E-03 | 1.382E-02 | CA2; CA4 |
| hsa05221 | Acute myeloid leukemia_Homo sapiens_hsa05221 | 6.992E-03 | 4.156E-02 | NFKB1; PPARD |
| hsa05203 | Viral carcinogenesis_Homo sapiens_hsa05203 | 1.032E-02 | 4.834E-02 | POLB; PKM; NFKB1 |
| hsa04923 | Regulation of lipolysis in adipocytes_Homo sapiens_hsa04923 | 6.756E-03 | 4.156E-02 | FABP4; TSHR |
| hsa05134 | Legionellosis_Homo sapiens_hsa05134 | 6.523E-03 | 4.156E-02 | NFKB1; TLR2 |
| hsa00051 | Fructose and mannose metabolism_Homo sapiens_hsa00051 | 2.250E-03 | 2.188E-02 | AKR1B10; AKR1B1 |
| hsa00561 | Glycerolipid metabolism_Homo sapiens_hsa00561 | 7.475E-03 | 4.209E-02 | AKR1B10; AKR1B1 |
| hsa05321 | Inflammatory bowel disease (IBD)_Homo sapiens_hsa05321 | 9.011E-03 | 4.821E-02 | NFKB1; TLR2 |
| hsa05230 | Central carbon metabolism in cancer_Homo sapiens_hsa05230 | 9.552E-03 | 4.834E-02 | PKM; HIF1A |
| hsa04920 | Adipocytokine signaling pathway_Homo sapiens_hsa04920 | 1.039E-02 | 4.834E-02 | PPARA; NFKB1 |
Human Diseases Associated with the Target Proteins of the Plant (Activity≤10μM)
Detailed Information of Human Diseases
| ICD10 Disease Category | Disease Name | ICD10 Code | Linked Targets |
|---|---|---|---|
| G00-G99: Diseases of the nervous system G00-G99 | Neurodegenerative disease | G30-G32 | MAPT |
| E00-E89: Endocrine, nutritional and metabolic diseases | Autoimmune diabetes | E08-E13 | TLR2 |
| A00-B99: Certain infectious and parasitic diseases | Fungal infections | B35-B49 | RAB9A |
| C00-D49: Neoplasms | Colorectal cancer | C18-C21 | MMP9 |
| C00-D49: Neoplasms | Renal cancer | C64 | CA9 |
| I00-I99: Diseases of the circulatory system | High blood pressure | I10-I16 | CA2 |
| I00-I99: Diseases of the circulatory system | Stroke | I61-I63, I80-I82 | MMP9 |
| NA: NA | Colour dead tissues | NA | PTPN1 |
| C00-D49: Neoplasms | Thyroid cancer diagnosis | C73 | TSHR |
| C00-D49: Neoplasms | Thyroid cancer | C73 | TSHR |
| E00-E89: Endocrine, nutritional and metabolic diseases | Pompe's disease | E74.02 | GAA |
| E00-E89: Endocrine, nutritional and metabolic diseases | Hyperlipidaemia | E78 | PPARD; HCAR2 |
| G00-G99: Diseases of the nervous system G00-G99 | Mild to moderate alzheimer disease | G30 | APP |
| E00-E89: Endocrine, nutritional and metabolic diseases | Non-insulin dependent diabetes | E11.9 | FFAR1 |
| E00-E89: Endocrine, nutritional and metabolic diseases | Diabetic neuropathy | E11.40 | AKR1B1 |
| E00-E89: Endocrine, nutritional and metabolic diseases | Diabetic nephropathy | E11.21 | MMP1 |
| E00-E89: Endocrine, nutritional and metabolic diseases | Diabetic cataract | E10.36, E11.36 | AKR1B1 |
| E00-E89: Endocrine, nutritional and metabolic diseases | Diabetic complication | E08-E13 | AKR1B1 |
| G00-G99: Diseases of the nervous system G00-G99 | Diagnostic imaging | G30, I73.9 | APP |
| M00-M99: Diseases of the musculoskeletal system and connective tissue | Gout | M10 | AKR1B1; PPARG |
| H00-H59: Diseases of the eye and adnexa | Glaucoma | H40-H42 | CA1; CA1; AKR1B1 |
| NA: NA | Geographic retinal atrophy | NA | APP |
| C00-D49: Neoplasms | Glioma | C71 | APP |
| G00-G99: Diseases of the nervous system G00-G99 | Pain | G64, G90.0, R52, G89 | PKM |
| C00-D49: Neoplasms | Pancreatic cancer | C25 | TLR2; MMP2 |
| M00-M99: Diseases of the musculoskeletal system and connective tissue | Osteoarthritis | M15-M19, M47 | MMP2 |
| E00-E89: Endocrine, nutritional and metabolic diseases | Dyslipidaemias | E78 | PPARD; PPARD |
| NA: NA | Dyslipidemia | NA | PPARD |
| W85-W99: Exposure to electric current, radiation and extreme ambient air temperature and pressure | Diagnostic test to differentiate primary and secondary hypothyroidism | W88 | TSHR |
| F01-F99: Mental, Behavioral and Neurodevelopmental disorders | Drug abuse | F10-F19 | PPARG |
| C00-D49: Neoplasms | Ovarian cancer | C56 | MMP2 |
| C00-D49: Neoplasms | Head and neck cancer | C07-C14, C32-C33 | AKR1B1 |
| E00-E89: Endocrine, nutritional and metabolic diseases | Diabetes | E23.2, N25.1 | PTPN1; FFAR1; AKR1B1; PPARG |
| I00-I99: Diseases of the circulatory system | Acute ischemic stroke | I61-I63 | HCAR2 |
| H00-H59: Diseases of the eye and adnexa | Open-angle glaucoma | H40-H42 | CA2; CA4 |
| H00-H59: Diseases of the eye and adnexa | Ocular inflammation | H16.229 | PPARG |
| H00-H59: Diseases of the eye and adnexa | Ocular hypertension | H40.0 | CA4; CA4 |
| E00-E89: Endocrine, nutritional and metabolic diseases | Amyloidosis | E85 | APP |
| F01-F99: Mental, Behavioral and Neurodevelopmental disorders | Major depressive disorder | F32, F33, M32 | HCAR2 |
| K00-K95: Diseases of the digestive system | Non-alcoholic fatty liver disease | K76.0 | PPARD; PPARG |
| C00-D49: Neoplasms | Solid tumours | C00-D48 | HIF1A; CA9; MMP9; TLR2; MMP2; PKM |
| C00-D49: Neoplasms | Melanoma | C43 | TLR2 |
| I00-I99: Diseases of the circulatory system | Neurological disease | I21, I22, R52, R52.1-R52.2, R60.9, G89 | APP |
| G00-G99: Diseases of the nervous system G00-G99 | Alzheimer disease | G30 | MAPT; APP; PPARG; PPARG |
| H00-H59: Diseases of the eye and adnexa | Age related macular degeneration | H35.3 | APP |
| M00-M99: Diseases of the musculoskeletal system and connective tissue | Rheumatoid arthritis | M05-M06 | MMP1; AKR1B1 |
| K00-K95: Diseases of the digestive system | Duodenal ulcers | K25-K27 | CA2; CA1 |
| E00-E89: Endocrine, nutritional and metabolic diseases | Metabolic disorders | E70-E89 | PPARD |
| I00-I99: Diseases of the circulatory system | Edema associated with congestive heart failure | I50, R60.9 | CA2 |
| NA: NA | Edema | NA | CA2 |
| N00-N99: Diseases of the genitourinary system | Endometriosis | N80 | PPARG |
| F01-F99: Mental, Behavioral and Neurodevelopmental disorders | Mild cognitive impairment | F06.7 | APP |
| C00-D49: Neoplasms | Myelodysplastic syndrome | D46 | TLR2 |
| I00-I99: Diseases of the circulatory system | Cardiovascular disorder | I00-I99 | HCAR2 |
| S00-T88: Injury, poisoning and certain other consequences of external causes | Radiation sickness | T66 | TLR2 |
| C00-D49: Neoplasms | Refractory renal cell carcinoma | C64 | PKM |
| K00-K95: Diseases of the digestive system | Ulcerative colitis | K51 | MMP9 |
| F01-F99: Mental, Behavioral and Neurodevelopmental disorders | Insomnia | F51.0, G47.0 | CA2 |
| K00-K95: Diseases of the digestive system | Inflammatory bowel disease | K50, K51 | PPARG |
| C00-D49: Neoplasms | Cancer | C00-C96 | HIF1A; CA1; CA9; MMP9; NFKB1; TLR2; MMP2; APP |
| C00-D49: Neoplasms | Renal cell carcinoma | NA | MMP2 |
| E00-E89: Endocrine, nutritional and metabolic diseases | Type 1 diabetes | E10 | PPARD; PPARG |
| E00-E89: Endocrine, nutritional and metabolic diseases | Type 2 diabetes | E11 | PTPN1; PTPN1; FFAR1; PPARD; NFKB1; HCAR2; PPARG; PPARG |
| S00-T88: Injury, poisoning and certain other consequences of external causes | Brain injury | S09.90 | APP |
| C00-D49: Neoplasms | Breast cancer | C50 | CA9 |
| C00-D49: Neoplasms | Prostate cancer | C61 | TLR2 |
| C00-D49: Neoplasms | Lymphoma | C81-C86 | HIF1A; CA9 |
| L00-L99: Diseases of the skin and subcutaneous tissue | Acne vulgaris | L70.0 | MMP2 |
| I00-I99: Diseases of the circulatory system | Pulmonary arterial hypertension | I27.0, I27.2 | HIF1A |
| C00-D49: Neoplasms | Lung cancer | C33-C34 | MMP2 |
| H00-H59: Diseases of the eye and adnexa | Macular degeneration | H35.3 | APP |
| C00-D49: Neoplasms | Clear cell renal cell carcinoma | C64 | CA9 |
| F01-F99: Mental, Behavioral and Neurodevelopmental disorders | Cognitive disorders | F01-F07, F04, F05, R41.3 | MAPT |
| E00-E89: Endocrine, nutritional and metabolic diseases | Obesity | E66 | PTPN1; PPARD; PPARD; PPARG |
| C00-D49: Neoplasms | Non-small-cell lung cancer | NA | MMP2 |
| F01-F99: Mental, Behavioral and Neurodevelopmental disorders | Nicotine dependence | F17 | PPARG |
| H00-H59: Diseases of the eye and adnexa | Chronic glaucoma | H40-H42 | CA1 |
| A00-B99: Certain infectious and parasitic diseases | Infections | A00-B99 | PTPN1 |
| G00-G99: Diseases of the nervous system G00-G99 | Central nervous system disease | G00-G99 | PPARD; MAPT |
| I00-I99: Diseases of the circulatory system | Cerebral amyloid angiopathy | I68.0 | APP |
| I00-I99: Diseases of the circulatory system | Arteriosclerosis | I70 | HCAR2 |
| M00-M99: Diseases of the musculoskeletal system and connective tissue | Arthritis | M00-M25 | MMP1 |
| I00-I99: Diseases of the circulatory system | Atherosclerosis | I70 | PPARD; HCAR2 |