NPASS Compound

Natural Product: NPC514143

Natural Product ID	NPC514143
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Tricin 7-O-glucuronide
IUPAC Name	(2~{S},3~{S},4~{S},5~{R},6~{S})-3,4,5-trihydroxy-6-[5-hydroxy-2-(4-hydroxy-3,5-dimethoxy-phenyl)-4-oxo-chromen-7-yl]oxy-tetrahydropyran-2-carboxylic acid
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 58 61 0 0 0 0 0 0 0 0999 V2000 -4.8754 -1.5908 1.8878 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6405 -1.4171 0.7055 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1972 -0.8461 -0.4597 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8991 -0.4510 -0.6450 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4742 0.1189 -1.8385 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0311 0.4076 -2.0126 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5124 0.8701 -3.1938 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1671 1.1018 -3.3139 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3282 1.5303 -4.4004 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6584 0.8673 -2.2387 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0381 1.0584 -2.2795 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5433 1.5268 -3.5055 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8574 0.8116 -1.2097 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2846 0.3482 -0.0156 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1163 0.0933 1.0547 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7454 -0.0729 2.3904 C 0 0 2 0 0 0 0 0 0 0 0 0 3.3517 0.8987 3.1834 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5697 0.5808 3.7022 C 0 0 2 0 0 0 0 0 0 0 0 0 5.4124 1.8197 3.6861 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5782 1.7169 4.1484 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9981 3.0313 3.2077 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2886 -0.4270 2.8431 C 0 0 1 0 0 0 0 0 0 0 0 0 6.5942 -0.5576 3.3315 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5337 -1.7305 2.9178 C 0 0 2 0 0 0 0 0 0 0 0 0 4.9089 -2.5752 1.8872 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0366 -1.4676 2.9114 C 0 0 1 0 0 0 0 0 0 0 0 0 2.4561 -1.6440 4.1429 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9199 0.1625 0.0137 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0844 0.4069 -1.0747 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2026 0.2014 -1.0076 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3931 0.2886 -2.8384 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7316 -0.1088 -2.6627 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6508 0.0586 -3.6521 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4545 0.6105 -4.9256 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1386 -0.6756 -1.4811 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4594 -1.0661 -1.3184 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5522 -2.1077 2.6175 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9929 -2.2281 1.7599 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6074 -0.6134 2.3466 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1565 -0.5820 0.1480 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1428 1.0529 -4.0208 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3360 2.4924 -3.7304 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9172 0.9755 -1.2925 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6570 0.0843 2.4783 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4555 0.2400 4.7484 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5929 3.8579 3.3367 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2717 -0.0360 1.8008 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1675 0.0019 2.7223 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7682 -2.2333 3.8755 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5042 -3.2730 2.2091 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5850 -2.1835 2.1996 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3061 -0.7915 4.6243 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4556 -0.1916 0.9222 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0889 0.7320 -3.7681 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2152 1.6902 -4.8031 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5653 0.1926 -5.4581 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3812 0.5629 -5.5495 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7912 -1.5224 -0.4708 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 8 10 1 0 10 11 2 0 11 12 1 0 11 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 2 0 19 21 1 0 18 22 1 0 22 23 1 0 22 24 1 0 24 25 1 0 24 26 1 0 26 27 1 0 14 28 1 0 28 29 2 0 29 30 1 0 5 31 2 0 31 32 1 0 32 33 1 0 33 34 1 0 32 35 2 0 35 36 1 0 35 3 1 0 30 6 1 0 29 10 1 0 26 16 1 0 1 37 1 0 1 38 1 0 1 39 1 0 4 40 1 0 7 41 1 0 12 42 1 0 13 43 1 0 16 44 1 6 18 45 1 1 21 46 1 0 22 47 1 6 23 48 1 0 24 49 1 1 25 50 1 0 26 51 1 6 27 52 1 0 28 53 1 0 31 54 1 0 34 55 1 0 34 56 1 0 34 57 1 0 36 58 1 0 M END

Standard InCHIKey	HJWFFBNADKDQPV-KHYDEXNFSA-N
Standard InCHI	InChI=1S/C23H22O13/c1-32-14-3-8(4-15(33-2)17(14)26)12-7-11(25)16-10(24)5-9(6-13(16)35-12)34-23-20(29)18(27)19(28)21(36-23)22(30)31/h3-7,18-21,23-24,26-29H,1-2H3,(H,30,31)/t18-,19-,20+,21-,23+/m0/s1
SMILES	COC1=CC(C2=CC(=O)C3=C(O)C=C(O[C@@H]4O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]4O)C=C3O2)=CC(OC)=C1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	506.11	Volume:	462.683 ? Van der Waals volume.
Dense:	1.094	LogP:	1.19 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.387 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.156 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	25.0
TPSA:	205.58 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	6.0	Rings:	4.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.264	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.025	Fsp³:	0.304
MCE-18:	93.333 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.388	Fluc inhibitor:	0.227 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.955 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.907 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.098	Promiscuous compounds:	0.443

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.057	MDCK Permeability:	-5.472
Pgp-inhibitor:	0.0	Pgp-substrate:	0.458
PAMPA:	0.998 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.426
20% Bioavailability (F20%):	0.019	30% Bioavailability (F30%):	0.159
50% Bioavailability (F50%):	0.935

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.99
Plasma Protein Binding (PPB):	83.383%	Volume Distribution (VD):	-0.356
Fu:	13.817% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.977
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.946
BSEP inhibitor:	0.031

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.005	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.005	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.03
HLM stability:	0.018 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

1.601

Half-life (T1/2):

4.443

ADMET: Toxicity

hERG Blockers:	0.014	hERG Blockers (10um):	0.062
Human Hepatotoxicity (H-HT):	0.54	Drug-induced Liver Injury (DILI):	0.992
AMES Toxicity:	0.613	Rat Oral Acute Toxicity:	0.062
Maximum Recommended Daily Dose:	0.073	Skin Sensitization:	0.933
Carcinogencity:	0.204	Eye Corrosion:	0.0
Eye Irritation:	0.784	Respiratory Toxicity:	0.115
Drug-induced Neurotoxicity:	0.002	Ototoxicity:	0.743
Hematotoxicity:	0.19	Drug-induced Nephrotoxicity:	0.607
Genotoxicity:	0.907	RPMI-8226 Immunitoxicity:	0.087
A549 Cytotoxicity:	0.05	Hek293 Cytotoxicity:	0.116
BCF:	0.22 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	2.928 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.154 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.382 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO18321	Medicago sativa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1104/pp.84.1.73]
NPO18321	Medicago sativa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12232319]
NPO18321	Medicago sativa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22208890]
NPO18321	Medicago sativa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO63016	Stipa lemmonii	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18321	Medicago sativa	Species	Fabaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO18321	Medicago sativa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO18321	Medicago sativa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18321	Medicago sativa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO18321	Medicago sativa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC514143 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	25743
0.1-0.2	21576
0.2-0.3	1909
0.3-0.4	454
0.4-0.5	130
0.5-0.6	37
0.6-0.7	5
0.7-0.8	0
0.8-0.85	3
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.84	Intermediate Similarity	NPC608742
0.8026	Intermediate Similarity	NPC282169
0.8026	Intermediate Similarity	NPC20505
0.6506	Remote Similarity	NPC237435
0.6429	Remote Similarity	NPC48479
0.6429	Remote Similarity	NPC43211
0.6207	Remote Similarity	NPC600989
0.6047	Remote Similarity	NPC115760
0.5978	Remote Similarity	NPC46202
0.5938	Remote Similarity	NPC253685
0.5814	Remote Similarity	NPC101191
0.5795	Remote Similarity	NPC311830
0.5747	Remote Similarity	NPC135277
0.5747	Remote Similarity	NPC210094
0.5684	Remote Similarity	NPC229409
0.5682	Remote Similarity	NPC601144
0.5682	Remote Similarity	NPC610187
0.5638	Remote Similarity	NPC64051
0.5581	Remote Similarity	NPC95090
0.5581	Remote Similarity	NPC27408
0.5529	Remote Similarity	NPC473043
0.5517	Remote Similarity	NPC181712
0.5506	Remote Similarity	NPC22832
0.5506	Remote Similarity	NPC243930
0.5465	Remote Similarity	NPC19709
0.5402	Remote Similarity	NPC189142
0.5402	Remote Similarity	NPC77660
0.5349	Remote Similarity	NPC331652
0.5333	Remote Similarity	NPC33265
0.5287	Remote Similarity	NPC261866
0.5287	Remote Similarity	NPC39360
0.5287	Remote Similarity	NPC29763
0.5287	Remote Similarity	NPC210003
0.5281	Remote Similarity	NPC27942
0.5275	Remote Similarity	NPC607707
0.5256	Remote Similarity	NPC137062
0.5253	Remote Similarity	NPC479765
0.5165	Remote Similarity	NPC264735
0.5152	Remote Similarity	NPC479766
0.5128	Remote Similarity	NPC177298
0.5111	Remote Similarity	NPC138927
0.5065	Remote Similarity	NPC108406
0.5055	Remote Similarity	NPC235260
0.5055	Remote Similarity	NPC155763
0.5054	Remote Similarity	NPC190003

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC514143 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4537
0.1-0.2	4545
0.2-0.3	58
0.3-0.4	8
0.4-0.5	1
0.5-0.6	0
0.6-0.7	1
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.6506	Remote Similarity	NPD4338	Clinical (unspecified phase)

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data