NPASS Compound

Natural Product: NPC500587

Natural Product ID	NPC500587
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5-hydroxy-6,7-dimethoxy-3-[4-[(2~{S},3~{S},4~{R},5~{R},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxyphenyl]chromen-4-one
IUPAC Name	5-hydroxy-6,7-dimethoxy-3-[4-[(2~{S},3~{S},4~{R},5~{R},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxyphenyl]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 58 61 0 0 0 0 0 0 0 0999 V2000 8.8399 -2.0251 0.0079 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3252 -0.7410 -0.3500 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9509 -0.5278 -0.3393 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0991 -1.5471 0.0134 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7408 -1.2885 0.0096 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2425 -0.0694 -0.3297 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1105 0.9196 -0.6742 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5577 2.1652 -1.0186 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4524 0.6909 -0.6785 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3041 1.7485 -1.0427 O 0 0 0 0 0 0 0 0 0 0 0 0 7.7828 2.6202 -0.0302 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8726 0.1472 -0.3203 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4402 1.2887 -0.6399 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0345 -0.8800 0.0340 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6049 -0.6636 0.0468 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0433 0.0018 -1.0005 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4064 0.2001 -0.9735 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2013 -0.2492 0.0911 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5369 0.0110 -0.0048 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5561 -0.3075 0.8818 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.5142 -1.1491 0.3193 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.1060 -0.5314 -0.7735 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.9270 -1.4822 -1.5884 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9582 -2.0642 -0.8813 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.9415 0.6229 -0.2328 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.7697 1.1706 -1.1828 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9317 1.6372 0.3100 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.5363 2.8073 0.6970 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2185 0.9515 1.4542 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.2099 1.8017 1.8847 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5700 -0.9046 1.1245 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2114 -1.0929 1.0803 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6097 -2.0789 0.3631 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9234 -2.2513 0.3434 O 0 0 0 0 0 0 0 0 0 0 0 0 8.5708 -2.1864 1.0713 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2534 -2.7751 -0.5889 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9115 -2.1036 -0.1677 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4300 -2.5348 0.2924 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5968 2.4407 -2.0095 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7098 3.1334 -0.3685 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0641 3.3884 0.2599 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0431 2.0147 0.8662 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5768 0.3498 -1.8262 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8470 0.7205 -1.8118 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1509 -0.8446 1.7610 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3193 -0.1067 -1.4171 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2570 -2.2335 -2.0209 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3436 -0.8887 -2.4510 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0536 -1.7474 0.0337 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4954 0.2606 0.6774 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6473 1.3451 -0.7450 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1886 1.7802 -0.4960 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1010 3.5543 0.1954 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8935 0.6193 2.2504 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2067 2.6770 1.4146 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1845 -1.2568 1.9565 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2638 -1.6083 1.8992 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0157 -2.9286 0.6508 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 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 1 0 6 12 1 0 12 13 2 0 12 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 22 25 1 0 25 26 1 0 25 27 1 0 27 28 1 0 27 29 1 0 29 30 1 0 18 31 1 0 31 32 2 0 14 33 2 0 33 34 1 0 9 3 1 0 32 15 1 0 34 5 1 0 29 20 1 0 1 35 1 0 1 36 1 0 1 37 1 0 4 38 1 0 8 39 1 0 11 40 1 0 11 41 1 0 11 42 1 0 16 43 1 0 17 44 1 0 20 45 1 1 22 46 1 6 23 47 1 0 23 48 1 0 24 49 1 0 25 50 1 1 26 51 1 0 27 52 1 6 28 53 1 0 29 54 1 1 30 55 1 0 31 56 1 0 32 57 1 0 33 58 1 0 M END

Standard InCHIKey	YIOGKKRAFIMIAE-GWIPIKLZSA-N
Standard InCHI	InChI=1S/C23H24O11/c1-30-14-7-13-16(19(27)22(14)31-2)17(25)12(9-32-13)10-3-5-11(6-4-10)33-23-21(29)20(28)18(26)15(8-24)34-23/h3-7,9,15,18,20-21,23-24,26-29H,8H2,1-2H3/t15-,18-,20+,21-,23+/m0/s1
SMILES	COC1=CC2=C(C(O)=C1OC)C(=O)C(C1=CC=C(O[C@@H]3O[C@@H](CO)[C@H](O)[C@@H](O)[C@@H]3O)C=C1)=CO2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	476.13	Volume:	447.739 ? Van der Waals volume.
Dense:	1.063	LogP:	0.786 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.383 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.117 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	24.0
TPSA:	168.28 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	5.0	Rings:	4.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.333	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.856	Fsp³:	0.348
MCE-18:	86.387 ? 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:	1	PAINS Alert:	0
Colloidal aggregators:	0.499	Fluc inhibitor:	0.34 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.8 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.707 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.083	Promiscuous compounds:	0.22

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.301	MDCK Permeability:	-5.413
Pgp-inhibitor:	0.005	Pgp-substrate:	0.386
PAMPA:	0.981 ? 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):	0.988
20% Bioavailability (F20%):	0.647	30% Bioavailability (F30%):	0.954
50% Bioavailability (F50%):	0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.068	MRP1:	0.599
Plasma Protein Binding (PPB):	87.823%	Volume Distribution (VD):	-0.101
Fu:	10.535% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.98
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.376
BSEP inhibitor:	0.027

ADMET: Metabolism

CYP1A2-inhibitor:	0.012	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.167	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.002	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.903
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.551
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):

2.401

Half-life (T1/2):

1.822

ADMET: Toxicity

hERG Blockers:	0.038	hERG Blockers (10um):	0.201
Human Hepatotoxicity (H-HT):	0.746	Drug-induced Liver Injury (DILI):	0.983
AMES Toxicity:	0.917	Rat Oral Acute Toxicity:	0.165
Maximum Recommended Daily Dose:	0.045	Skin Sensitization:	0.956
Carcinogencity:	0.251	Eye Corrosion:	0.0
Eye Irritation:	0.336	Respiratory Toxicity:	0.056
Drug-induced Neurotoxicity:	0.056	Ototoxicity:	0.842
Hematotoxicity:	0.537	Drug-induced Nephrotoxicity:	0.934
Genotoxicity:	0.694	RPMI-8226 Immunitoxicity:	0.284
A549 Cytotoxicity:	0.542	Hek293 Cytotoxicity:	0.172
BCF:	0.624 ? 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:	3.399 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.838 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.051 ? 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
NPO24343	Dalbergia spinosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24343	Dalbergia spinosa	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 NPC500587 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	19258
0.1-0.2	26325
0.2-0.3	3043
0.3-0.4	904
0.4-0.5	261
0.5-0.6	36
0.6-0.7	23
0.7-0.8	0
0.8-0.85	3
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8333	Intermediate Similarity	NPC205076
0.8243	Intermediate Similarity	NPC307518
0.8194	Intermediate Similarity	NPC73511
0.7733	Intermediate Similarity	NPC224462
0.7662	Intermediate Similarity	NPC48773
0.7333	Intermediate Similarity	NPC156457
0.7297	Intermediate Similarity	NPC45165
0.7297	Intermediate Similarity	NPC135345
0.6883	Remote Similarity	NPC197896
0.6883	Remote Similarity	NPC258035
0.6883	Remote Similarity	NPC313163
0.6753	Remote Similarity	NPC58053
0.675	Remote Similarity	NPC229729
0.6667	Remote Similarity	NPC105511
0.6667	Remote Similarity	NPC161749
0.6667	Remote Similarity	NPC234739
0.6623	Remote Similarity	NPC160515
0.65	Remote Similarity	NPC100720
0.6456	Remote Similarity	NPC603782
0.642	Remote Similarity	NPC481043
0.6375	Remote Similarity	NPC186807
0.622	Remote Similarity	NPC479402
0.6145	Remote Similarity	NPC601607
0.6098	Remote Similarity	NPC138540
0.6047	Remote Similarity	NPC487212
0.6026	Remote Similarity	NPC25547
0.6024	Remote Similarity	NPC479401
0.6024	Remote Similarity	NPC80140
0.6024	Remote Similarity	NPC609451
0.6	Remote Similarity	NPC216769
0.6	Remote Similarity	NPC479407
0.5952	Remote Similarity	NPC605067
0.5843	Remote Similarity	NPC479405
0.5783	Remote Similarity	NPC24043
0.5778	Remote Similarity	NPC479404
0.5765	Remote Similarity	NPC21666
0.5732	Remote Similarity	NPC348541
0.5698	Remote Similarity	NPC479406
0.5663	Remote Similarity	NPC93337
0.5595	Remote Similarity	NPC105025
0.5595	Remote Similarity	NPC45638
0.5591	Remote Similarity	NPC257714
0.5542	Remote Similarity	NPC259070
0.5542	Remote Similarity	NPC211014
0.5529	Remote Similarity	NPC117260
0.5529	Remote Similarity	NPC201292
0.5517	Remote Similarity	NPC607201
0.5476	Remote Similarity	NPC487213
0.5476	Remote Similarity	NPC95090
0.5476	Remote Similarity	NPC27408
0.5465	Remote Similarity	NPC488071
0.5412	Remote Similarity	NPC603655
0.5357	Remote Similarity	NPC289667
0.5341	Remote Similarity	NPC602805
0.5281	Remote Similarity	NPC488072
0.5227	Remote Similarity	NPC243930
0.5205	Remote Similarity	NPC116632
0.5205	Remote Similarity	NPC35763
0.5176	Remote Similarity	NPC143851
0.5172	Remote Similarity	NPC472459
0.5169	Remote Similarity	NPC607707
0.5161	Remote Similarity	NPC475155
0.5158	Remote Similarity	NPC479403
0.5116	Remote Similarity	NPC64305
0.5056	Remote Similarity	NPC22832
0.5056	Remote Similarity	NPC148710
0.5056	Remote Similarity	NPC486578

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC500587 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4575
0.1-0.2	4458
0.2-0.3	100
0.3-0.4	13
0.4-0.5	3
0.5-0.6	0
0.6-0.7	1
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
0.6667	Remote Similarity	NPD4381	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