NPASS Compound

Natural Product: NPC511899

Natural Product ID	NPC511899
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5,7-dihydroxy-3-(4-hydroxyphenyl)-8-[(2~{S},3~{R},4~{R},5~{S},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]chromen-4-one
IUPAC Name	5,7-dihydroxy-3-(4-hydroxyphenyl)-8-[(2~{S},3~{R},4~{R},5~{S},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]chromen-4-one
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 51 54 0 0 0 0 0 0 0 0999 V2000 3.4917 -0.1202 -1.9391 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5896 -0.1463 -1.0614 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9163 -0.3690 0.2612 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2716 -0.5799 0.7105 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7249 0.0670 1.8300 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0291 -0.1104 2.2970 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8690 -0.9710 1.5894 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1857 -1.1646 2.0413 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4300 -1.6275 0.4647 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1153 -1.4193 0.0336 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8349 -0.3778 1.1540 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6062 -0.1849 0.7351 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3075 0.0250 -0.5191 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0206 0.2142 -0.8355 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0543 0.1754 0.2308 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.1446 -0.4798 -0.2545 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3725 0.0507 -0.0231 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.4521 -0.9649 -0.2803 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4818 -1.4498 -1.5607 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4337 0.3666 1.4795 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.7567 -0.6486 2.1187 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5889 1.6248 1.6070 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.3595 2.6709 1.0936 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3044 1.5108 0.8474 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.2807 1.8110 1.7611 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3194 0.4363 -2.1755 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6562 0.6260 -2.4893 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3405 0.4667 -3.1427 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9606 0.2764 -2.7975 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9874 0.2965 -3.7277 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3005 0.0525 -1.4762 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1189 0.7468 2.4201 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4043 0.3901 3.1765 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8291 -0.3977 2.0086 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1135 -2.2809 -0.0478 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7820 -1.9455 -0.8579 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0401 -0.5492 2.2076 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6258 -0.4785 1.0494 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5566 1.0075 -0.5430 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3967 -1.8209 0.4210 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4416 -0.4679 -0.0815 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5972 -2.4310 -1.6181 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4531 0.5367 1.8216 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2924 -1.1452 2.7822 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4638 1.8131 2.6868 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7404 3.3622 0.7040 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2688 2.2774 0.0464 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2693 1.1658 2.5109 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0155 0.1279 -3.2944 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6062 0.6417 -4.1752 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3851 -0.6090 -3.9770 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 7 9 1 0 9 10 2 0 3 11 2 0 11 12 1 0 12 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 17 20 1 0 20 21 1 0 20 22 1 0 22 23 1 0 22 24 1 0 24 25 1 0 14 26 1 0 26 27 1 0 26 28 2 0 28 29 1 0 29 30 1 0 29 31 2 0 31 2 1 0 10 4 1 0 31 13 1 0 24 15 1 0 5 32 1 0 6 33 1 0 8 34 1 0 9 35 1 0 10 36 1 0 11 37 1 0 15 38 1 1 17 39 1 6 18 40 1 0 18 41 1 0 19 42 1 0 20 43 1 1 21 44 1 0 22 45 1 1 23 46 1 0 24 47 1 6 25 48 1 0 27 49 1 0 28 50 1 0 30 51 1 0 M END

Standard InCHIKey	HIWJJOYYZFELEZ-TVBXGXBUSA-N
Standard InCHI	InChI=1S/C21H20O10/c22-6-13-17(27)18(28)19(29)21(31-13)15-12(25)5-11(24)14-16(26)10(7-30-20(14)15)8-1-3-9(23)4-2-8/h1-5,7,13,17-19,21-25,27-29H,6H2/t13-,17+,18-,19+,21-/m0/s1
SMILES	O=C1C(C2=CC=C(O)C=C2)=COC2=C([C@@H]3O[C@@H](CO)[C@@H](O)[C@H](O)[C@H]3O)C(O)=CC(O)=C12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	432.11	Volume:	404.357 ? Van der Waals volume.
Dense:	1.069	LogP:	0.52 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.014 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.24 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	24.0
TPSA:	181.05 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	7.0	Rings:	4.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.3	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.005	Fsp³:	0.286
MCE-18:	87.63 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.586	Fluc inhibitor:	0.158 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.749 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.692 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.259	Promiscuous compounds:	0.327

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.456	MDCK Permeability:	-5.085
Pgp-inhibitor:	0.0	Pgp-substrate:	0.554
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):	0.355
20% Bioavailability (F20%):	0.351	30% Bioavailability (F30%):	0.963
50% Bioavailability (F50%):	0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.005	MRP1:	0.384
Plasma Protein Binding (PPB):	87.284%	Volume Distribution (VD):	-0.05
Fu:	12.025% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.221
OATP1B3 inhibitor:	0.667	BCRP inhibitor:	0.092
BSEP inhibitor:	0.004

ADMET: Metabolism

CYP1A2-inhibitor:	0.006	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.285	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.003
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.189
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.88
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):

3.226

Half-life (T1/2):

3.912

ADMET: Toxicity

hERG Blockers:	0.025	hERG Blockers (10um):	0.291
Human Hepatotoxicity (H-HT):	0.497	Drug-induced Liver Injury (DILI):	0.744
AMES Toxicity:	0.614	Rat Oral Acute Toxicity:	0.125
Maximum Recommended Daily Dose:	0.093	Skin Sensitization:	0.839
Carcinogencity:	0.154	Eye Corrosion:	0.0
Eye Irritation:	0.66	Respiratory Toxicity:	0.055
Drug-induced Neurotoxicity:	0.014	Ototoxicity:	0.852
Hematotoxicity:	0.081	Drug-induced Nephrotoxicity:	0.405
Genotoxicity:	0.763	RPMI-8226 Immunitoxicity:	0.089
A549 Cytotoxicity:	0.252	Hek293 Cytotoxicity:	0.295
BCF:	0.48 ? 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:	2.993 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.345 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.662 ? 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
NPO19934	Genista ephedroides	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1021/np980112s]
NPO1830	Dalbergia sissoo	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18154272]
NPO1830	Dalbergia sissoo	Species	Fabaceae	Eukaryota	leaves	n.a.	n.a.	PMID[22212722]
NPO51366	Spartidium saharae	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1674	Dalbergia nitidula	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8707.1	Pueraria montana var. lobata	Varieties	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1830	Dalbergia sissoo	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19934	Genista ephedroides	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25469	Lupinus luteus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25469	Lupinus luteus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1674	Dalbergia nitidula	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1830	Dalbergia sissoo	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1674	Dalbergia nitidula	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1830	Dalbergia sissoo	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO25469	Lupinus luteus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8707.1	Pueraria montana var. lobata	Varieties	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO25469	Lupinus luteus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO1830	Dalbergia sissoo	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO8707.1	Pueraria montana var. lobata	Varieties	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO8707.1	Pueraria montana var. lobata	Varieties	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19934	Genista ephedroides	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1830	Dalbergia sissoo	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1674	Dalbergia nitidula	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25469	Lupinus luteus	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 NPC511899 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	21042
0.1-0.2	26090
0.2-0.3	2348
0.3-0.4	304
0.4-0.5	63
0.5-0.6	7
0.6-0.7	2
0.7-0.8	1
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC177308
0.7606	Intermediate Similarity	NPC124478
0.6533	Remote Similarity	NPC209846
0.6164	Remote Similarity	NPC55597
0.5823	Remote Similarity	NPC117418
0.5789	Remote Similarity	NPC307052
0.56	Remote Similarity	NPC222298
0.5455	Remote Similarity	NPC607879
0.5395	Remote Similarity	NPC604003
0.5333	Remote Similarity	NPC144118
0.5181	Remote Similarity	NPC112701

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC511899 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5198
0.1-0.2	3882
0.2-0.3	63
0.3-0.4	3
0.4-0.5	3
0.5-0.6	0
0.6-0.7	0
0.7-0.8	1
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
0.7606	Intermediate Similarity	NPD4380	Phase 2

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