NPASS Compound

Natural Product: NPC590144

Natural Product ID	NPC590144
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2R,3R)-2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3,4-dihydro-2H-1-benzopyran-3-yl acetate
IUPAC Name	[(2~{R},3~{R})-2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-chroman-3-yl] acetate
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 40 42 0 0 0 0 0 0 0 0999 V2000 -0.6404 4.5194 0.3476 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1800 3.2874 0.5437 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2474 3.2813 1.2198 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1710 2.0656 -0.0013 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5693 0.8987 0.1613 C 0 0 2 0 0 0 0 0 0 0 0 0 1.1770 0.3763 -1.1160 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1250 -0.7070 -0.7406 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3232 -0.8150 -1.3812 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7349 0.0426 -2.3927 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1626 -1.8478 -0.9835 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7889 -2.7235 0.0205 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5846 -3.7665 0.4542 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5505 -2.5759 0.6508 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7173 -1.5625 0.2665 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4775 -1.3966 0.8815 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1793 -0.1473 0.9342 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6088 -0.2484 0.5424 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5884 0.3886 1.2794 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9315 0.3085 0.9328 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3446 -0.4129 -0.1654 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7020 -0.4901 -0.5103 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3717 -1.0508 -0.9047 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7713 -1.7846 -2.0181 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0383 -0.9669 -0.5545 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3102 5.3055 1.0560 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7222 4.2910 0.4282 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4435 4.8849 -0.6694 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4566 1.1789 0.7995 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7332 1.2133 -1.5796 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4661 -0.0292 -1.8276 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3281 0.8202 -2.0901 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1300 -2.0108 -1.4337 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9872 -3.8107 1.3909 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2314 -3.2526 1.4455 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1391 0.1632 2.0210 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2534 0.9622 2.1537 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6852 0.8179 1.5273 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1300 -1.4101 -0.5638 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6185 -2.3075 -2.0143 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3211 -1.4892 -1.1733 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 2 0 8 9 1 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 2 0 18 19 1 0 19 20 2 0 20 21 1 0 20 22 1 0 22 23 1 0 22 24 2 0 16 5 1 0 24 17 1 0 14 7 1 0 1 25 1 0 1 26 1 0 1 27 1 0 5 28 1 1 6 29 1 0 6 30 1 0 9 31 1 0 10 32 1 0 12 33 1 0 13 34 1 0 16 35 1 1 18 36 1 0 19 37 1 0 21 38 1 0 23 39 1 0 24 40 1 0 M END

Standard InCHIKey	CCTIBFOBERZTCX-IAGOWNOFSA-N
Standard InCHI	InChI=1S/C17H16O7/c1-8(18)23-16-7-11-13(21)5-10(19)6-15(11)24-17(16)9-2-3-12(20)14(22)4-9/h2-6,16-17,19-22H,7H2,1H3/t16-,17-/m1/s1
SMILES	CC(=O)O[C@@H]1CC2=C(O)C=C(O)C=C2O[C@@H]1C1=CC=C(O)C(O)=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	332.09	Volume:	319.995 ? Van der Waals volume.
Dense:	1.038	LogP:	1.524 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.728 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.351 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	18.0
TPSA:	116.45 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.491	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.384	Fsp³:	0.235
MCE-18:	62.429 ? 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:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.601	Fluc inhibitor:	0.515 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.06 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.243 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.508	Promiscuous compounds:	0.193

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.997	MDCK Permeability:	-4.944
Pgp-inhibitor:	0.219	Pgp-substrate:	0.279
PAMPA:	0.119 ? 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):	0.027
20% Bioavailability (F20%):	0.99	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.006	MRP1:	0.89
Plasma Protein Binding (PPB):	78.503%	Volume Distribution (VD):	-0.417
Fu:	26.853% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.951	BCRP inhibitor:	0.126
BSEP inhibitor:	0.047

ADMET: Metabolism

CYP1A2-inhibitor:	0.943	CYP1A2-substrate:	0.009
CYP2C19-inhibitor:	0.072	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.152	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.013	CYP2D6-substrate:	0.417
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.967
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.953
HLM stability:	0.185 ? 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):

12.073

Half-life (T1/2):

1.656

ADMET: Toxicity

hERG Blockers:	0.076	hERG Blockers (10um):	0.636
Human Hepatotoxicity (H-HT):	0.518	Drug-induced Liver Injury (DILI):	0.605
AMES Toxicity:	0.726	Rat Oral Acute Toxicity:	0.594
Maximum Recommended Daily Dose:	0.653	Skin Sensitization:	0.993
Carcinogencity:	0.265	Eye Corrosion:	0.086
Eye Irritation:	0.979	Respiratory Toxicity:	0.741
Drug-induced Neurotoxicity:	0.114	Ototoxicity:	0.461
Hematotoxicity:	0.115	Drug-induced Nephrotoxicity:	0.066
Genotoxicity:	0.99	RPMI-8226 Immunitoxicity:	0.03
A549 Cytotoxicity:	0.941	Hek293 Cytotoxicity:	0.713
BCF:	0.765 ? 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:	3.43 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.531 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.063 ? 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
NPO8626	Rhizophora stylosa	Species	Rhizophoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8626	Rhizophora stylosa	Species	Rhizophoraceae	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 NPC590144 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	13606
0.1-0.2	29359
0.2-0.3	6184
0.3-0.4	548
0.4-0.5	108
0.5-0.6	28
0.6-0.7	12
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
0.7018	Intermediate Similarity	NPC474656
0.7018	Intermediate Similarity	NPC38779
0.7018	Intermediate Similarity	NPC114179
0.7018	Intermediate Similarity	NPC68324
0.7018	Intermediate Similarity	NPC289322
0.7018	Intermediate Similarity	NPC160512
0.6727	Remote Similarity	NPC471744
0.6667	Remote Similarity	NPC601196
0.6557	Remote Similarity	NPC40222
0.6557	Remote Similarity	NPC268515
0.6349	Remote Similarity	NPC53889
0.6167	Remote Similarity	NPC156818
0.6111	Remote Similarity	NPC261619
0.6111	Remote Similarity	NPC61477
0.6111	Remote Similarity	NPC78770
0.6111	Remote Similarity	NPC219876
0.6111	Remote Similarity	NPC126029
0.6111	Remote Similarity	NPC15658
0.5862	Remote Similarity	NPC291948
0.5862	Remote Similarity	NPC104983
0.5862	Remote Similarity	NPC250436
0.5862	Remote Similarity	NPC300845
0.5862	Remote Similarity	NPC88803
0.5538	Remote Similarity	NPC262328
0.5538	Remote Similarity	NPC87777
0.5278	Remote Similarity	NPC98583
0.5246	Remote Similarity	NPC112418
0.5179	Remote Similarity	NPC207179
0.5179	Remote Similarity	NPC167571
0.5179	Remote Similarity	NPC278552
0.5167	Remote Similarity	NPC609747
0.5152	Remote Similarity	NPC58190
0.5152	Remote Similarity	NPC108811
0.5152	Remote Similarity	NPC170103
0.5152	Remote Similarity	NPC236202
0.5152	Remote Similarity	NPC262911
0.5152	Remote Similarity	NPC202742
0.5085	Remote Similarity	NPC321011
0.5085	Remote Similarity	NPC294852
0.5085	Remote Similarity	NPC188679
0.5075	Remote Similarity	NPC246202
0.5075	Remote Similarity	NPC224161
0.5075	Remote Similarity	NPC46335
0.5075	Remote Similarity	NPC87317
0.5075	Remote Similarity	NPC279406
0.5075	Remote Similarity	NPC486519

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC590144 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3254
0.1-0.2	5695
0.2-0.3	185
0.3-0.4	12
0.4-0.5	1
0.5-0.6	1
0.6-0.7	2
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
0.6111	Remote Similarity	NPD1612	Clinical (unspecified phase)
0.6111	Remote Similarity	NPD1613	Phase 4
0.5862	Remote Similarity	NPD4868	Phase 3

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