NPASS Compound

Natural Product: NPC513093

Natural Product ID	NPC513093
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{R})-2-(2,5-dihydroxyphenyl)-5,7-dihydroxy-chroman-4-one
IUPAC Name	(2~{R})-2-(2,5-dihydroxyphenyl)-5,7-dihydroxy-chroman-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 33 35 0 0 0 0 0 0 0 0999 V2000 1.8181 -2.9801 -0.4893 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3038 -1.8318 -0.4122 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1758 -1.6277 -0.4420 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4994 -0.5872 0.6025 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8941 -0.0909 0.4742 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2183 0.9949 -0.3132 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5118 1.4661 -0.4408 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7931 2.5786 -1.2569 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5262 0.8477 0.2302 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2469 -0.2387 1.0264 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9326 -0.7027 1.1445 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6194 -1.7973 1.9407 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3574 0.5086 0.5764 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6917 0.4780 0.2125 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5240 1.5763 0.3375 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8480 1.4939 -0.0399 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6789 2.6232 0.0952 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3832 0.3281 -0.5493 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5337 -0.7534 -0.6644 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9862 -1.9689 -1.1675 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2034 -0.6899 -0.2913 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6979 -2.5635 -0.2114 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4624 -1.2921 -1.4658 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3627 -1.0970 1.6001 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4238 1.4934 -0.8498 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7863 2.3597 -2.2654 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5383 1.2244 0.1241 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0312 -0.7615 1.5801 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0090 -2.7014 1.6295 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0960 2.4869 0.7380 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2927 3.5602 -0.0161 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4155 0.2224 -0.8567 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5965 -2.5581 -0.5800 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 1 0 5 6 2 0 6 7 1 0 7 8 1 0 7 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 4 13 1 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 1 0 16 18 2 0 18 19 1 0 19 20 1 0 19 21 2 0 21 2 1 0 11 5 1 0 21 14 1 0 3 22 1 0 3 23 1 0 4 24 1 1 6 25 1 0 8 26 1 0 9 27 1 0 10 28 1 0 12 29 1 0 15 30 1 0 17 31 1 0 18 32 1 0 20 33 1 0 M END

Standard InCHIKey	XVXXIRQXOYAJAF-CYBMUJFWSA-N
Standard InCHI	InChI=1S/C15H12O6/c16-7-1-2-10(18)9(3-7)13-6-12(20)15-11(19)4-8(17)5-14(15)21-13/h1-5,13,16-19H,6H2/t13-/m1/s1
SMILES	O=C1C[C@H](C2=CC(O)=CC=C2O)OC2=CC(O)=CC(O)=C12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	288.06	Volume:	276.613 ? Van der Waals volume.
Dense:	1.041	LogP:	1.796 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.049 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.121 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	18.0
TPSA:	107.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.599	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.053	Fsp³:	0.133
MCE-18:	58.235 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.665	Fluc inhibitor:	0.727 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.37 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.221 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.507	Promiscuous compounds:	0.072

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.162	MDCK Permeability:	-4.789
Pgp-inhibitor:	0.063	Pgp-substrate:	0.043
PAMPA:	0.511 ? 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):	0.005
20% Bioavailability (F20%):	0.324	30% Bioavailability (F30%):	0.955
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.865
Plasma Protein Binding (PPB):	90.212%	Volume Distribution (VD):	-0.112
Fu:	10.457% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.977
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.858
BSEP inhibitor:	0.433

ADMET: Metabolism

CYP1A2-inhibitor:	0.979	CYP1A2-substrate:	0.747
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.912
CYP2C9-inhibitor:	0.004	CYP2C9-substrate:	0.003
CYP2D6-inhibitor:	0.012	CYP2D6-substrate:	0.994
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.912
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.992
HLM stability:	0.96 ? 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):

10.643

Half-life (T1/2):

1.544

ADMET: Toxicity

hERG Blockers:	0.055	hERG Blockers (10um):	0.474
Human Hepatotoxicity (H-HT):	0.671	Drug-induced Liver Injury (DILI):	0.522
AMES Toxicity:	0.757	Rat Oral Acute Toxicity:	0.707
Maximum Recommended Daily Dose:	0.843	Skin Sensitization:	0.838
Carcinogencity:	0.527	Eye Corrosion:	0.057
Eye Irritation:	0.995	Respiratory Toxicity:	0.952
Drug-induced Neurotoxicity:	0.354	Ototoxicity:	0.27
Hematotoxicity:	0.067	Drug-induced Nephrotoxicity:	0.435
Genotoxicity:	0.994	RPMI-8226 Immunitoxicity:	0.184
A549 Cytotoxicity:	0.858	Hek293 Cytotoxicity:	0.819
BCF:	1.352 ? 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:	3.737 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.625 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.931 ? 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
NPO30455	Inula cappa	Species	Asteraceae	Eukaryota	Whole Plant	Yulin County, Guangxi Province, China	2012-SEP	PMID[26444098]
NPO30455	Inula cappa	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO50346	Scutellaria amabilis HARA	Genus	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20367	Tanacetum sibiricum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20367	Tanacetum sibiricum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO20367	Tanacetum sibiricum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO20367	Tanacetum sibiricum	Species	Asteraceae	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 NPC513093 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	28066
0.1-0.2	18675
0.2-0.3	2470
0.3-0.4	466
0.4-0.5	133
0.5-0.6	25
0.6-0.7	16
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	Natural Product ID
0.75	Intermediate Similarity	NPC295261
0.75	Intermediate Similarity	NPC296490
0.72	Intermediate Similarity	NPC107586
0.6939	Remote Similarity	NPC182421
0.68	Remote Similarity	NPC32441
0.68	Remote Similarity	NPC243083
0.68	Remote Similarity	NPC13768
0.68	Remote Similarity	NPC287246
0.68	Remote Similarity	NPC79943
0.68	Remote Similarity	NPC12296
0.6731	Remote Similarity	NPC321011
0.6731	Remote Similarity	NPC294852
0.6731	Remote Similarity	NPC188679
0.6226	Remote Similarity	NPC274784
0.6226	Remote Similarity	NPC338131
0.6226	Remote Similarity	NPC20709
0.6182	Remote Similarity	NPC302950
0.6111	Remote Similarity	NPC606962
0.6	Remote Similarity	NPC310135
0.5965	Remote Similarity	NPC236637
0.5667	Remote Similarity	NPC477841
0.5593	Remote Similarity	NPC258630
0.5574	Remote Similarity	NPC109223
0.5574	Remote Similarity	NPC10937
0.5556	Remote Similarity	NPC472460
0.5556	Remote Similarity	NPC134783
0.5484	Remote Similarity	NPC106976
0.5397	Remote Similarity	NPC174953
0.5357	Remote Similarity	NPC73028
0.5323	Remote Similarity	NPC17170
0.5231	Remote Similarity	NPC470890
0.5224	Remote Similarity	NPC96408
0.5224	Remote Similarity	NPC610511
0.5217	Remote Similarity	NPC58805
0.5156	Remote Similarity	NPC108456
0.5156	Remote Similarity	NPC85121
0.5152	Remote Similarity	NPC473990
0.5152	Remote Similarity	NPC88964
0.5152	Remote Similarity	NPC611447
0.5147	Remote Similarity	NPC279650
0.5098	Remote Similarity	NPC482958
0.5088	Remote Similarity	NPC329203
0.5088	Remote Similarity	NPC222342
0.5075	Remote Similarity	NPC118256

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC513093 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5530
0.1-0.2	3561
0.2-0.3	45
0.3-0.4	10
0.4-0.5	1
0.5-0.6	0
0.6-0.7	3
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
0.68	Remote Similarity	NPD1550	Phase 2
0.68	Remote Similarity	NPD1552	Clinical (unspecified phase)
0.6182	Remote Similarity	NPD1934	Phase 0

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