NPASS Compound

Natural Product: NPC592473

Natural Product ID	NPC592473
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{R})-5,7-dihydroxy-2-[4-hydroxy-3-[(2~{S},3~{R},4~{S},5~{S},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-phenyl]chroman-4-one
IUPAC Name	(2~{R})-5,7-dihydroxy-2-[4-hydroxy-3-[(2~{S},3~{R},4~{S},5~{S},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-phenyl]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 54 57 0 0 0 0 0 0 0 0999 V2000 -3.8458 2.6786 -1.2079 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7577 1.4895 -0.8030 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4323 0.9022 -0.4779 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6865 -0.1396 0.6161 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.4513 -0.8514 0.9759 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5198 -1.9937 1.7399 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3941 -2.7051 2.1093 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8321 -2.2218 1.6770 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0065 -2.8842 2.0094 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9530 -1.0703 0.9021 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2206 -0.6927 0.5363 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5988 0.4121 -0.2309 C 0 0 2 0 0 0 0 0 0 0 0 0 3.2043 0.0032 -1.3912 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5306 -0.2698 -1.3477 C 0 0 1 0 0 0 0 0 0 0 0 0 5.2535 0.6364 -2.3459 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6395 0.3836 -2.3315 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1822 -0.2835 -0.0171 C 0 0 1 0 0 0 0 0 0 0 0 0 6.5722 -0.1087 -0.2150 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7425 0.7667 0.9375 C 0 0 2 0 0 0 0 0 0 0 0 0 4.6420 0.1791 2.2142 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4268 1.3674 0.5881 C 0 0 1 0 0 0 0 0 0 0 0 0 3.5361 2.6174 -0.0467 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1965 -0.3917 0.5566 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7080 -1.0469 0.1765 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9378 -0.5407 -0.1752 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1196 -1.2722 -0.0460 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3501 -0.7597 -0.4002 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.5258 -1.4962 -0.2683 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.3733 0.5255 -0.8961 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2229 1.2756 -1.0366 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2654 2.5754 -1.5405 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9995 0.7366 -0.6732 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8226 1.7065 -0.0173 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9518 0.4423 -1.3614 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1051 0.4326 1.4701 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4921 -2.3374 2.0567 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4615 -3.6119 2.7171 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9833 -3.7015 2.6086 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6940 0.9746 -0.5234 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6639 -1.3094 -1.7796 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0356 1.7089 -2.1619 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9265 0.4242 -3.3846 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1241 1.1990 -2.6140 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0982 -1.3132 0.4358 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0311 -0.9417 -0.4176 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5183 1.5777 1.0637 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2529 -0.6050 2.2512 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8636 1.5645 1.5243 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1867 3.1416 0.4662 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1599 0.4970 -0.0363 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0282 -2.2658 0.3471 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5426 -2.3050 0.3212 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3082 0.9655 -1.1848 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0606 3.1959 -1.3687 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 2 0 8 9 1 0 8 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 14 17 1 0 17 18 1 0 17 19 1 0 19 20 1 0 19 21 1 0 21 22 1 0 10 23 2 0 4 24 1 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 1 0 27 29 2 0 29 30 1 0 30 31 1 0 30 32 2 0 32 2 1 0 23 5 1 0 32 25 1 0 21 12 1 0 3 33 1 0 3 34 1 0 4 35 1 1 6 36 1 0 7 37 1 0 9 38 1 0 12 39 1 6 14 40 1 6 15 41 1 0 15 42 1 0 16 43 1 0 17 44 1 1 18 45 1 0 19 46 1 1 20 47 1 0 21 48 1 1 22 49 1 0 23 50 1 0 26 51 1 0 28 52 1 0 29 53 1 0 31 54 1 0 M END

Standard InCHIKey	KTDWFYOXQQWERW-ZEDPFBHNSA-N
Standard InCHI	InChI=1S/C21H22O11/c22-7-16-18(27)19(28)20(29)21(32-16)31-14-3-8(1-2-10(14)24)13-6-12(26)17-11(25)4-9(23)5-15(17)30-13/h1-5,13,16,18-25,27-29H,6-7H2/t13-,16+,18-,19+,20-,21-/m1/s1
SMILES	O=C1C[C@H](C2=CC=C(O)C(O[C@@H]3O[C@@H](CO)[C@@H](O)[C@H](O)[C@H]3O)=C2)OC2=CC(O)=CC(O)=C12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	450.12	Volume:	415.784 ? Van der Waals volume.
Dense:	1.083	LogP:	0.677 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.19 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.984 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	24.0
TPSA:	186.37 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	7.0	Rings:	4.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.324	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.127	Fsp³:	0.381
MCE-18:	90.552 ? 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:	1
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.621	Fluc inhibitor:	0.498 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.14 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.559 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.23	Promiscuous compounds:	0.327

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.614	MDCK Permeability:	-5.09
Pgp-inhibitor:	0.001	Pgp-substrate:	0.16
PAMPA:	0.994 ? 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):	0.024
20% Bioavailability (F20%):	0.183	30% Bioavailability (F30%):	0.982
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.552
Plasma Protein Binding (PPB):	89.106%	Volume Distribution (VD):	-0.205
Fu:	10.161% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.958
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.919
BSEP inhibitor:	0.043

ADMET: Metabolism

CYP1A2-inhibitor:	0.01	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.013
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.01
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.722
HLM stability:	0.017 ? 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):

3.579

Half-life (T1/2):

3.032

ADMET: Toxicity

hERG Blockers:	0.024	hERG Blockers (10um):	0.218
Human Hepatotoxicity (H-HT):	0.788	Drug-induced Liver Injury (DILI):	0.901
AMES Toxicity:	0.876	Rat Oral Acute Toxicity:	0.189
Maximum Recommended Daily Dose:	0.164	Skin Sensitization:	0.988
Carcinogencity:	0.156	Eye Corrosion:	0.0
Eye Irritation:	0.727	Respiratory Toxicity:	0.124
Drug-induced Neurotoxicity:	0.027	Ototoxicity:	0.904
Hematotoxicity:	0.146	Drug-induced Nephrotoxicity:	0.854
Genotoxicity:	0.989	RPMI-8226 Immunitoxicity:	0.186
A549 Cytotoxicity:	0.665	Hek293 Cytotoxicity:	0.413
BCF:	0.434 ? 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:	3.018 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.443 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.657 ? 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
NPO12422	Pinus massoniana	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32100544]
NPO12422	Pinus massoniana	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO53418	Helosis guyanensis	Genus	Balanophoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12422	Pinus massoniana	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12422	Pinus massoniana	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12422	Pinus massoniana	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12422	Pinus massoniana	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO12422	Pinus massoniana	Species	Pinaceae	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 NPC592473 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	18620
0.1-0.2	25908
0.2-0.3	4026
0.3-0.4	982
0.4-0.5	256
0.5-0.6	43
0.6-0.7	13
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
0.7778	Intermediate Similarity	NPC26195
0.7733	Intermediate Similarity	NPC236934
0.6842	Remote Similarity	NPC39351
0.6667	Remote Similarity	NPC236637
0.6456	Remote Similarity	NPC29830
0.6456	Remote Similarity	NPC181014
0.6364	Remote Similarity	NPC169248
0.6364	Remote Similarity	NPC168789
0.6364	Remote Similarity	NPC72649
0.6282	Remote Similarity	NPC97052
0.6203	Remote Similarity	NPC219163
0.6082	Remote Similarity	NPC483820
0.6081	Remote Similarity	NPC199335
0.6076	Remote Similarity	NPC170475
0.6	Remote Similarity	NPC190217
0.5976	Remote Similarity	NPC5778
0.5882	Remote Similarity	NPC158188
0.5875	Remote Similarity	NPC259182
0.5867	Remote Similarity	NPC477240
0.5802	Remote Similarity	NPC471457
0.5778	Remote Similarity	NPC70441
0.5732	Remote Similarity	NPC206378
0.5732	Remote Similarity	NPC257963
0.5679	Remote Similarity	NPC45400
0.5647	Remote Similarity	NPC602605
0.5616	Remote Similarity	NPC205054
0.56	Remote Similarity	NPC106025
0.56	Remote Similarity	NPC488528
0.5526	Remote Similarity	NPC477841
0.5488	Remote Similarity	NPC88484
0.5429	Remote Similarity	NPC32441
0.5429	Remote Similarity	NPC79943
0.5368	Remote Similarity	NPC199079
0.5366	Remote Similarity	NPC160156
0.5366	Remote Similarity	NPC92565
0.5349	Remote Similarity	NPC472383
0.5263	Remote Similarity	NPC326037
0.5263	Remote Similarity	NPC13858
0.5208	Remote Similarity	NPC261254
0.5205	Remote Similarity	NPC321011
0.5205	Remote Similarity	NPC294852
0.5205	Remote Similarity	NPC188679
0.519	Remote Similarity	NPC469661
0.519	Remote Similarity	NPC65530
0.5172	Remote Similarity	NPC472381
0.5165	Remote Similarity	NPC105283
0.5132	Remote Similarity	NPC210015
0.5114	Remote Similarity	NPC479540
0.5067	Remote Similarity	NPC302950
0.5057	Remote Similarity	NPC36916
0.5057	Remote Similarity	NPC36
0.5057	Remote Similarity	NPC7154
0.5057	Remote Similarity	NPC125039
0.5057	Remote Similarity	NPC7688
0.5054	Remote Similarity	NPC142860
0.5054	Remote Similarity	NPC152538
0.5054	Remote Similarity	NPC246469
0.5054	Remote Similarity	NPC89088

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC592473 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4773
0.1-0.2	4287
0.2-0.3	70
0.3-0.4	13
0.4-0.5	1
0.5-0.6	5
0.6-0.7	0
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
0.5429	Remote Similarity	NPD1552	Clinical (unspecified phase)
0.5067	Remote Similarity	NPD1934	Phase 0
0.5057	Remote Similarity	NPD6166	Phase 2
0.5057	Remote Similarity	NPD6167	Clinical (unspecified phase)
0.5057	Remote Similarity	NPD6168	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