NPASS Compound

Natural Product: NPC521157

Natural Product ID	NPC521157
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5-hydroxy-3-(2-hydroxyphenyl)-7-[(2~{S},3~{R},4~{S},5~{S},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-chromen-4-one
IUPAC Name	5-hydroxy-3-(2-hydroxyphenyl)-7-[(2~{S},3~{R},4~{S},5~{S},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-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 51 54 0 0 0 0 0 0 0 0999 V2000 3.9061 1.4699 0.3715 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4340 0.4615 -0.2055 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2368 -0.4595 -0.8592 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6775 -0.2673 -0.8880 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3286 0.4369 -1.8768 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6972 0.5965 -1.8679 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4375 0.0431 -0.8519 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8231 -0.6668 0.1528 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4523 -0.8059 0.1111 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8839 -1.5430 1.1676 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5880 -1.5223 -1.4518 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2840 -1.6588 -1.4025 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4982 -0.7959 -0.7865 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1406 -0.9524 -0.7441 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7101 -0.0349 -0.0877 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0627 -0.2612 -0.0891 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0151 0.5175 0.4917 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.7149 -0.1708 1.5015 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8582 -0.7983 1.0135 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.2766 -1.8359 2.0326 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4038 -2.5260 1.6587 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9578 0.2321 0.7940 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.6622 0.5044 1.9523 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2388 1.5000 0.3497 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.0800 2.3588 -0.3279 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0501 1.0606 -0.4886 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.5386 2.2197 -1.0810 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1553 1.0558 0.5319 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2267 1.2010 0.4800 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8181 2.2911 1.0953 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0543 0.3083 -0.1588 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7590 0.8920 -2.7048 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2071 1.1636 -2.6668 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5202 0.1543 -0.8211 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4098 -1.1157 0.9743 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6861 -2.5204 0.9379 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1972 -2.2729 -1.9799 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3169 -1.8028 -1.2246 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5909 1.3990 0.9951 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6478 -1.2653 0.0376 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4369 -2.5785 2.0708 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3296 -1.4044 3.0522 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5454 -3.2484 2.3186 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6613 -0.0899 -0.0120 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9468 -0.2972 2.4461 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8153 1.9460 1.2739 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0172 2.1015 -0.0603 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3093 0.3518 -1.2728 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0381 2.5028 -1.8632 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7372 1.8234 1.0677 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8503 2.3029 2.1071 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 2 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 3 11 2 0 11 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 19 22 1 0 22 23 1 0 22 24 1 0 24 25 1 0 24 26 1 0 26 27 1 0 15 28 2 0 28 29 1 0 29 30 1 0 29 31 2 0 31 2 1 0 9 4 1 0 31 13 1 0 26 17 1 0 5 32 1 0 6 33 1 0 7 34 1 0 8 35 1 0 10 36 1 0 11 37 1 0 14 38 1 0 17 39 1 1 19 40 1 6 20 41 1 0 20 42 1 0 21 43 1 0 22 44 1 6 23 45 1 0 24 46 1 1 25 47 1 0 26 48 1 6 27 49 1 0 28 50 1 0 30 51 1 0 M END

Standard InCHIKey	VEEIDCZENCXYKD-FZHKGVQDSA-N
Standard InCHI	InChI=1S/C21H20O10/c22-7-15-18(26)19(27)20(28)21(31-15)30-9-5-13(24)16-14(6-9)29-8-11(17(16)25)10-3-1-2-4-12(10)23/h1-6,8,15,18-24,26-28H,7H2/t15-,18+,19-,20+,21+/m0/s1
SMILES	O=C1C(C2=CC=CC=C2O)=COC2=CC(O[C@@H]3O[C@@H](CO)[C@@H](O)[C@H](O)[C@H]3O)=CC(O)=C12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	432.11	Volume:	404.357 ? Van der Waals volume.
Dense:	1.069	LogP:	0.922 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.411 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.708 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	24.0
TPSA:	170.05 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	6.0	Rings:	4.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.331	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.882	Fsp³:	0.286
MCE-18:	84.259 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.572	Fluc inhibitor:	0.255 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.848 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.616 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.254	Promiscuous compounds:	0.389

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.383	MDCK Permeability:	-5.208
Pgp-inhibitor:	0.001	Pgp-substrate:	0.419
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):	0.399
20% Bioavailability (F20%):	0.262	30% Bioavailability (F30%):	0.932
50% Bioavailability (F50%):	0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.321
Plasma Protein Binding (PPB):	83.486%	Volume Distribution (VD):	-0.281
Fu:	17.103% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.856
OATP1B3 inhibitor:	0.99	BCRP inhibitor:	0.478
BSEP inhibitor:	0.046

ADMET: Metabolism

CYP1A2-inhibitor:	0.005	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:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.059
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.008
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):

2.343

Half-life (T1/2):

2.716

ADMET: Toxicity

hERG Blockers:	0.016	hERG Blockers (10um):	0.21
Human Hepatotoxicity (H-HT):	0.583	Drug-induced Liver Injury (DILI):	0.92
AMES Toxicity:	0.804	Rat Oral Acute Toxicity:	0.09
Maximum Recommended Daily Dose:	0.044	Skin Sensitization:	0.948
Carcinogencity:	0.143	Eye Corrosion:	0.0
Eye Irritation:	0.48	Respiratory Toxicity:	0.044
Drug-induced Neurotoxicity:	0.004	Ototoxicity:	0.859
Hematotoxicity:	0.119	Drug-induced Nephrotoxicity:	0.751
Genotoxicity:	0.916	RPMI-8226 Immunitoxicity:	0.122
A549 Cytotoxicity:	0.233	Hek293 Cytotoxicity:	0.169
BCF:	0.433 ? 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:	3.071 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.658 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.749 ? 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
NPO18252	Cajanus cajan	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[136119]
NPO18252	Cajanus cajan	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19299148]
NPO18252	Cajanus cajan	Species	Fabaceae	Eukaryota	n.a.	leaf	n.a.	PMID[24680612]
NPO18252	Cajanus cajan	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18252	Cajanus cajan	Species	Fabaceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO18252	Cajanus cajan	Species	Fabaceae	Eukaryota	Seed	n.a.	n.a.	Database[FooDB]
NPO18252	Cajanus cajan	Species	Fabaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO18252	Cajanus cajan	Species	Fabaceae	Eukaryota	Seeds	n.a.		Database[Phenol-Explorer]
NPO18252	Cajanus cajan	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 NPC521157 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	23498
0.1-0.2	22865
0.2-0.3	2437
0.3-0.4	788
0.4-0.5	200
0.5-0.6	55
0.6-0.7	9
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8592	High Similarity	NPC234739
0.8493	Intermediate Similarity	NPC80140
0.7838	Intermediate Similarity	NPC197896
0.7838	Intermediate Similarity	NPC313163
0.7273	Intermediate Similarity	NPC73511
0.7176	Intermediate Similarity	NPC479403
0.6962	Remote Similarity	NPC138540
0.6628	Remote Similarity	NPC479405
0.6582	Remote Similarity	NPC348541
0.6552	Remote Similarity	NPC479404
0.6463	Remote Similarity	NPC479402
0.6456	Remote Similarity	NPC160515
0.631	Remote Similarity	NPC479406
0.6098	Remote Similarity	NPC156457
0.6071	Remote Similarity	NPC479401
0.5952	Remote Similarity	NPC205076
0.5904	Remote Similarity	NPC161749
0.5897	Remote Similarity	NPC191154
0.5783	Remote Similarity	NPC289667
0.5783	Remote Similarity	NPC39360
0.5783	Remote Similarity	NPC29763
0.5783	Remote Similarity	NPC210003
0.5765	Remote Similarity	NPC100720
0.573	Remote Similarity	NPC487212
0.5714	Remote Similarity	NPC297987
0.5714	Remote Similarity	NPC95090
0.5714	Remote Similarity	NPC277205
0.5714	Remote Similarity	NPC27408
0.5714	Remote Similarity	NPC37919
0.5714	Remote Similarity	NPC136042
0.5714	Remote Similarity	NPC303913
0.5714	Remote Similarity	NPC323593
0.5714	Remote Similarity	NPC203500
0.5714	Remote Similarity	NPC189142
0.5714	Remote Similarity	NPC77660
0.5698	Remote Similarity	NPC307938
0.5698	Remote Similarity	NPC224462
0.5682	Remote Similarity	NPC48773
0.5647	Remote Similarity	NPC84362
0.5632	Remote Similarity	NPC243930
0.5632	Remote Similarity	NPC601144
0.5625	Remote Similarity	NPC134819
0.5568	Remote Similarity	NPC307518
0.5568	Remote Similarity	NPC311830
0.5529	Remote Similarity	NPC105511
0.5529	Remote Similarity	NPC258035
0.5517	Remote Similarity	NPC481043
0.5517	Remote Similarity	NPC285197
0.5506	Remote Similarity	NPC479407
0.5476	Remote Similarity	NPC45165
0.5455	Remote Similarity	NPC22832
0.5455	Remote Similarity	NPC229729
0.5412	Remote Similarity	NPC261866
0.5395	Remote Similarity	NPC90665
0.5393	Remote Similarity	NPC116458
0.5393	Remote Similarity	NPC246943
0.5393	Remote Similarity	NPC605784
0.5393	Remote Similarity	NPC607707
0.5294	Remote Similarity	NPC135345
0.5281	Remote Similarity	NPC486578
0.5281	Remote Similarity	NPC610187
0.5227	Remote Similarity	NPC60966
0.5222	Remote Similarity	NPC607201
0.5217	Remote Similarity	NPC251417
0.5172	Remote Similarity	NPC487213
0.5165	Remote Similarity	NPC601586
0.5114	Remote Similarity	NPC22195
0.5114	Remote Similarity	NPC21190
0.5111	Remote Similarity	NPC601607
0.5104	Remote Similarity	NPC64425

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC521157 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5253
0.1-0.2	3822
0.2-0.3	60
0.3-0.4	10
0.4-0.5	4
0.5-0.6	1
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
0.5904	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