NPASS Compound

Natural Product: NPC509473

Natural Product ID	NPC509473
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	[(2~{R},3~{S},4~{S},5~{R},6~{S})-6-[5,6-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-chromen-7-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-yl]methyl acetate
IUPAC Name	[(2~{R},3~{S},4~{S},5~{R},6~{S})-6-[5,6-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-chromen-7-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-yl]methyl 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 57 60 0 0 0 0 0 0 0 0999 V2000 -5.5595 4.4999 0.2413 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8632 3.2314 0.6683 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7196 3.2509 1.1609 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5171 2.0375 0.5041 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9326 0.8173 0.8740 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6704 0.5178 0.1137 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.1404 -0.7067 0.5229 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1328 -1.1068 -0.3650 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4942 -2.2233 0.1535 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1590 -2.2757 0.4192 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7563 -1.2749 0.2295 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1195 -1.4167 0.5324 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5735 -2.6028 1.0418 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6763 -3.6265 1.2431 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1845 -4.8103 1.7616 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3465 -3.4741 0.9425 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5178 -4.5390 1.1647 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9279 -2.7066 1.3294 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3702 -3.7876 1.7990 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7593 -1.6211 1.0938 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2304 -0.4718 0.5838 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0696 0.6903 0.3221 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4847 1.8492 -0.2017 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2188 2.9753 -0.4698 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5589 3.0079 -0.2338 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3215 4.1457 -0.5009 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1665 1.8874 0.2804 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4085 0.7480 0.5489 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9591 -0.4318 0.3344 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7694 -1.5765 -1.6887 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0918 -1.0183 -2.7709 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1778 -1.0176 -1.7008 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.9266 -1.6522 -0.7003 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0630 0.4538 -1.3655 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.0982 1.0331 -2.1749 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3255 4.6191 -0.8394 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6523 4.3562 0.3620 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1982 5.3404 0.8514 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7372 0.7978 1.9819 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7162 0.0366 0.7060 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9236 1.3255 0.2113 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4377 -0.2949 -0.5276 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4555 -0.3112 -0.1718 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6021 -5.6388 1.7860 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2581 -4.4840 1.8428 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8001 -1.7459 1.3310 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4273 1.8720 -0.4053 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7508 3.8606 -0.8739 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3075 4.1633 -0.3752 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2219 1.8778 0.4790 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9174 -0.0939 0.9450 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8271 -2.6622 -1.7574 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1203 -1.0353 -2.6446 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6779 -1.1844 -2.6756 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6103 -2.5881 -0.5876 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0089 1.0002 -1.5466 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2878 1.9842 -2.3638 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 1 0 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 14 16 2 0 16 17 1 0 13 18 1 0 18 19 2 0 18 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 25 27 1 0 27 28 2 0 21 29 1 0 8 30 1 0 30 31 1 0 30 32 1 0 32 33 1 0 32 34 1 0 34 35 1 0 34 6 1 0 16 10 1 0 28 22 1 0 29 12 1 0 1 36 1 0 1 37 1 0 1 38 1 0 5 39 1 0 5 40 1 0 6 41 1 6 8 42 1 6 11 43 1 0 15 44 1 0 17 45 1 0 20 46 1 0 23 47 1 0 24 48 1 0 26 49 1 0 27 50 1 0 28 51 1 0 30 52 1 6 31 53 1 0 32 54 1 6 33 55 1 0 34 56 1 1 35 57 1 0 M END

Standard InCHIKey	KRVNKBZMLFULDG-MTHGGYLLSA-N
Standard InCHI	InChI=1S/C23H22O12/c1-9(24)32-8-16-19(28)21(30)22(31)23(35-16)34-15-7-14-17(20(29)18(15)27)12(26)6-13(33-14)10-2-4-11(25)5-3-10/h2-7,16,19,21-23,25,27-31H,8H2,1H3/t16-,19-,21+,22-,23-/m1/s1
SMILES	CC(=O)OC[C@H]1O[C@@H](OC2=CC3=C(C(O)=C2O)C(=O)C=C(C2=CC=C(O)C=C2)O3)[C@H](O)[C@@H](O)[C@@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	490.11	Volume:	453.893 ? Van der Waals volume.
Dense:	1.08	LogP:	0.787 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.178 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.599 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	25.0
TPSA:	196.35 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	6.0	Rings:	4.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.212	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.004	Fsp³:	0.304
MCE-18:	90.0 ? 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:	0.502	Fluc inhibitor:	0.314 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.926 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.936 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.058	Promiscuous compounds:	0.754

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.337	MDCK Permeability:	-5.175
Pgp-inhibitor:	0.001	Pgp-substrate:	0.546
PAMPA:	0.998 ? 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):	0.109
20% Bioavailability (F20%):	0.684	30% Bioavailability (F30%):	0.992
50% Bioavailability (F50%):	0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.456
Plasma Protein Binding (PPB):	83.04%	Volume Distribution (VD):	-0.057
Fu:	16.119% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.993
OATP1B3 inhibitor:	0.995	BCRP inhibitor:	0.821
BSEP inhibitor:	0.158

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.073
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.012
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.98
HLM stability:	0.1 ? 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):

2.675

Half-life (T1/2):

2.913

ADMET: Toxicity

hERG Blockers:	0.019	hERG Blockers (10um):	0.235
Human Hepatotoxicity (H-HT):	0.469	Drug-induced Liver Injury (DILI):	0.934
AMES Toxicity:	0.826	Rat Oral Acute Toxicity:	0.107
Maximum Recommended Daily Dose:	0.114	Skin Sensitization:	0.98
Carcinogencity:	0.237	Eye Corrosion:	0.0
Eye Irritation:	0.822	Respiratory Toxicity:	0.019
Drug-induced Neurotoxicity:	0.011	Ototoxicity:	0.408
Hematotoxicity:	0.098	Drug-induced Nephrotoxicity:	0.309
Genotoxicity:	0.958	RPMI-8226 Immunitoxicity:	0.1
A549 Cytotoxicity:	0.461	Hek293 Cytotoxicity:	0.339
BCF:	0.49 ? 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:	3.126 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.479 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.947 ? 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
NPO63799	Halophila ovalis	Species	Hydrocharitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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 NPC509473 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	15339
0.1-0.2	30614
0.2-0.3	2846
0.3-0.4	698
0.4-0.5	263
0.5-0.6	67
0.6-0.7	17
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8	Intermediate Similarity	NPC477848
0.7778	Intermediate Similarity	NPC172807
0.7564	Intermediate Similarity	NPC146792
0.686	Remote Similarity	NPC254540
0.6744	Remote Similarity	NPC211594
0.6667	Remote Similarity	NPC64051
0.6627	Remote Similarity	NPC58716
0.6585	Remote Similarity	NPC45618
0.6517	Remote Similarity	NPC44931
0.6489	Remote Similarity	NPC298171
0.6452	Remote Similarity	NPC270675
0.6452	Remote Similarity	NPC195685
0.6395	Remote Similarity	NPC43211
0.6316	Remote Similarity	NPC101636
0.6289	Remote Similarity	NPC599948
0.625	Remote Similarity	NPC472994
0.6162	Remote Similarity	NPC472993
0.6071	Remote Similarity	NPC331652
0.6047	Remote Similarity	NPC84265
0.6	Remote Similarity	NPC229409
0.5977	Remote Similarity	NPC27942
0.5859	Remote Similarity	NPC603856
0.5814	Remote Similarity	NPC39360
0.5814	Remote Similarity	NPC29763
0.5814	Remote Similarity	NPC210003
0.5789	Remote Similarity	NPC46202
0.5747	Remote Similarity	NPC93337
0.5745	Remote Similarity	NPC473512
0.5745	Remote Similarity	NPC22062
0.5745	Remote Similarity	NPC129827
0.5745	Remote Similarity	NPC473634
0.5745	Remote Similarity	NPC210073
0.5745	Remote Similarity	NPC138811
0.5733	Remote Similarity	NPC198826
0.5714	Remote Similarity	NPC477629
0.5684	Remote Similarity	NPC204693
0.5682	Remote Similarity	NPC105025
0.5667	Remote Similarity	NPC181616
0.5652	Remote Similarity	NPC116864
0.5652	Remote Similarity	NPC244776
0.5612	Remote Similarity	NPC488089
0.5579	Remote Similarity	NPC3583
0.5567	Remote Similarity	NPC470443
0.5556	Remote Similarity	NPC237435
0.5543	Remote Similarity	NPC190003
0.5514	Remote Similarity	NPC298666
0.551	Remote Similarity	NPC473623
0.551	Remote Similarity	NPC209296
0.5506	Remote Similarity	NPC245014
0.5464	Remote Similarity	NPC153755
0.5408	Remote Similarity	NPC65711
0.54	Remote Similarity	NPC80068
0.5354	Remote Similarity	NPC483707
0.534	Remote Similarity	NPC11468
0.5281	Remote Similarity	NPC19709
0.5281	Remote Similarity	NPC83283
0.5275	Remote Similarity	NPC198324
0.5258	Remote Similarity	NPC233994
0.5208	Remote Similarity	NPC609888
0.5204	Remote Similarity	NPC186816
0.5192	Remote Similarity	NPC121703
0.5165	Remote Similarity	NPC181712
0.5165	Remote Similarity	NPC610763
0.5161	Remote Similarity	NPC115760
0.5161	Remote Similarity	NPC226722
0.5161	Remote Similarity	NPC601144
0.5158	Remote Similarity	NPC4390
0.5146	Remote Similarity	NPC179862
0.5132	Remote Similarity	NPC192229
0.5111	Remote Similarity	NPC58053
0.5102	Remote Similarity	NPC65563
0.5102	Remote Similarity	NPC470949
0.51	Remote Similarity	NPC211532
0.51	Remote Similarity	NPC488364
0.5098	Remote Similarity	NPC470447
0.5098	Remote Similarity	NPC85751
0.5098	Remote Similarity	NPC19240
0.5094	Remote Similarity	NPC480796
0.5093	Remote Similarity	NPC488087
0.5055	Remote Similarity	NPC95090
0.5055	Remote Similarity	NPC27408
0.5055	Remote Similarity	NPC259152
0.5055	Remote Similarity	NPC189142
0.5055	Remote Similarity	NPC77660
0.5052	Remote Similarity	NPC295613
0.5052	Remote Similarity	NPC473657
0.5049	Remote Similarity	NPC36138

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC509473 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4546
0.1-0.2	4513
0.2-0.3	79
0.3-0.4	5
0.4-0.5	5
0.5-0.6	2
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
0.5556	Remote Similarity	NPD4338	Clinical (unspecified phase)
0.551	Remote Similarity	NPD7054	Phase 4

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