NPASS Compound

Natural Product: NPC514637

Natural Product ID	NPC514637
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{S},3~{S},4~{S},5~{S},6~{S})-6-[2-(3,4-dihydroxy-5-methoxy-phenyl)-5-hydroxy-4-oxo-chromen-7-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid
IUPAC Name	(2~{S},3~{S},4~{S},5~{S},6~{S})-6-[2-(3,4-dihydroxy-5-methoxy-phenyl)-5-hydroxy-4-oxo-chromen-7-yl]oxy-3,4,5-trihydroxy-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 55 58 0 0 0 0 0 0 0 0999 V2000 4.0612 -1.9170 -3.0945 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3463 -1.4610 -2.6799 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4243 -0.6015 -1.5930 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3104 -0.1755 -0.9045 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3871 0.6823 0.1804 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1462 1.1003 0.8752 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1473 1.9471 1.9568 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0030 2.3461 2.6147 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9832 3.1076 3.5899 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8030 1.8449 2.1300 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3990 2.1781 2.7114 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3473 3.0492 3.8174 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5674 1.6838 2.2314 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5711 0.8215 1.1304 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7883 0.3714 0.7132 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0902 -0.4927 -0.3512 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.7668 0.2356 -1.2953 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1198 0.1295 -1.3301 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.8404 0.6900 -0.1843 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2647 1.2497 0.7885 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.2260 0.6312 -0.1111 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4772 -1.3008 -1.6534 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.0918 -1.5083 -2.9893 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8212 -2.2904 -0.7599 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.8404 -2.8765 0.0316 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7258 -1.7714 0.0861 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.2071 -1.5964 1.3909 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3622 0.5026 0.5664 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8562 1.0003 1.0443 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9833 0.6596 0.4630 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6352 1.1063 0.5593 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7893 0.6954 -0.1152 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0448 1.1280 0.2737 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6738 -0.1578 -1.1891 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7941 -0.6016 -1.9012 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3265 -1.0877 -3.1547 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7047 -2.6155 -2.3089 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1291 -2.4921 -4.0359 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3246 -0.5071 -1.1994 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0937 2.3279 2.3205 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2470 2.5555 4.7181 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4837 1.9662 2.7109 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1238 -0.7732 -0.8343 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4521 0.7158 -2.2412 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7431 0.6601 0.7587 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5782 -1.3821 -1.6423 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8159 -1.2796 -3.6247 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4698 -3.1410 -1.4089 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4752 -3.5804 0.6232 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9559 -2.5946 0.1824 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5745 -1.8949 2.0767 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3173 -0.1587 -0.2841 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7624 1.7677 1.3869 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3354 1.2619 1.2164 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6784 -0.1577 -1.6908 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 32 34 2 0 34 35 1 0 34 3 1 0 30 6 1 0 29 10 1 0 26 16 1 0 1 36 1 0 1 37 1 0 1 38 1 0 4 39 1 0 7 40 1 0 12 41 1 0 13 42 1 0 16 43 1 6 18 44 1 6 21 45 1 0 22 46 1 6 23 47 1 0 24 48 1 6 25 49 1 0 26 50 1 1 27 51 1 0 28 52 1 0 31 53 1 0 33 54 1 0 35 55 1 0 M END

Standard InCHIKey	VIYRBNJECSXYSN-SPNOPHAYSA-N
Standard InCHI	InChI=1S/C22H20O13/c1-32-14-3-7(2-11(25)16(14)26)12-6-10(24)15-9(23)4-8(5-13(15)34-12)33-22-19(29)17(27)18(28)20(35-22)21(30)31/h2-6,17-20,22-23,25-29H,1H3,(H,30,31)/t17-,18-,19-,20-,22+/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(O)=C1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	492.09	Volume:	445.387 ? Van der Waals volume.
Dense:	1.105	LogP:	0.844 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.146 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.815 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	25.0
TPSA:	216.58 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	7.0	Rings:	4.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.231	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.086	Fsp³:	0.273
MCE-18:	94.0 ? 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:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.442	Fluc inhibitor:	0.233 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.975 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.927 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.125	Promiscuous compounds:	0.489

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.195	MDCK Permeability:	-5.392
Pgp-inhibitor:	0.0	Pgp-substrate:	0.664
PAMPA:	1.0 ? 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):	0.802
20% Bioavailability (F20%):	0.891	30% Bioavailability (F30%):	0.97
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.996
Plasma Protein Binding (PPB):	78.779%	Volume Distribution (VD):	-0.251
Fu:	17.456% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.295
OATP1B3 inhibitor:	0.952	BCRP inhibitor:	0.466
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.265	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:	0.385
HLM stability:	0.001 ? 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):

1.728

Half-life (T1/2):

4.189

ADMET: Toxicity

hERG Blockers:	0.011	hERG Blockers (10um):	0.064
Human Hepatotoxicity (H-HT):	0.564	Drug-induced Liver Injury (DILI):	0.99
AMES Toxicity:	0.81	Rat Oral Acute Toxicity:	0.119
Maximum Recommended Daily Dose:	0.151	Skin Sensitization:	0.996
Carcinogencity:	0.211	Eye Corrosion:	0.0
Eye Irritation:	0.861	Respiratory Toxicity:	0.284
Drug-induced Neurotoxicity:	0.003	Ototoxicity:	0.766
Hematotoxicity:	0.316	Drug-induced Nephrotoxicity:	0.688
Genotoxicity:	0.954	RPMI-8226 Immunitoxicity:	0.066
A549 Cytotoxicity:	0.563	Hek293 Cytotoxicity:	0.173
BCF:	0.221 ? 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:	2.848 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.27 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.374 ? 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]
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 NPC514637 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	25923
0.1-0.2	21485
0.2-0.3	1819
0.3-0.4	467
0.4-0.5	117
0.5-0.6	38
0.6-0.7	5
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8182	Intermediate Similarity	NPC20505
0.8077	Intermediate Similarity	NPC608742
0.7722	Intermediate Similarity	NPC282169
0.6471	Remote Similarity	NPC237435
0.6395	Remote Similarity	NPC43211
0.618	Remote Similarity	NPC600989
0.6082	Remote Similarity	NPC253685
0.6023	Remote Similarity	NPC115760
0.5909	Remote Similarity	NPC135277
0.5833	Remote Similarity	NPC229409
0.5789	Remote Similarity	NPC46202
0.5698	Remote Similarity	NPC473043
0.5632	Remote Similarity	NPC19709
0.5618	Remote Similarity	NPC101191
0.5604	Remote Similarity	NPC311830
0.5568	Remote Similarity	NPC189142
0.5568	Remote Similarity	NPC77660
0.5556	Remote Similarity	NPC210094
0.5526	Remote Similarity	NPC48479
0.5495	Remote Similarity	NPC22832
0.5495	Remote Similarity	NPC601144
0.5495	Remote Similarity	NPC610187
0.5464	Remote Similarity	NPC64051
0.5393	Remote Similarity	NPC95090
0.5393	Remote Similarity	NPC27408
0.5333	Remote Similarity	NPC181712
0.5326	Remote Similarity	NPC243930
0.5316	Remote Similarity	NPC177298
0.5281	Remote Similarity	NPC261866
0.5275	Remote Similarity	NPC138927
0.5256	Remote Similarity	NPC108406
0.5217	Remote Similarity	NPC235260
0.5217	Remote Similarity	NPC49344
0.5217	Remote Similarity	NPC155763
0.5213	Remote Similarity	NPC190003
0.5169	Remote Similarity	NPC331652
0.5128	Remote Similarity	NPC33265
0.5125	Remote Similarity	NPC58382
0.5111	Remote Similarity	NPC39360
0.5111	Remote Similarity	NPC29763
0.5111	Remote Similarity	NPC210003
0.5109	Remote Similarity	NPC27942
0.5106	Remote Similarity	NPC607707
0.5104	Remote Similarity	NPC606546
0.5098	Remote Similarity	NPC479765
0.5062	Remote Similarity	NPC137062

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC514637 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4713
0.1-0.2	4371
0.2-0.3	58
0.3-0.4	6
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
0.6471	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